NEW YORK CITY, THURSDAY, OCTOBER 6, 2016

Patient-Centered CHARCOT-MARIE-TOOTH SUMMIT 1 Welcome Letter 2 Schedule 4 Event Speakers and Panelists 32 Abstracts/Research Studies

Thank you to PCORI

The Hereditary Neuropathy Foundation (HNF) would like to thank the Patient-Centered Outcomes Research Institute (PCORI) for nominating HNF for the PCORI’s Eugene Washington PCORI Engagement Award.

HNF is grateful for the support of PCORI for this ground-breaking Summit which include patients with all forms of Inherited Peripheral Neuropathies (INP's), caregivers, clinicians, researchers, funding agencies, and industry to discuss the barriers and opportunities impacting the translation of patient-reported outcomes into objective measures.

The Summit you are attending today was partially funded by this award and was instrumental in the success of the Summit. HNF-CURE.ORG 1

WELCOME TO THE 1ST HNF Patient-Centered Charcot-Marie-Tooth Summit!

We are thrilled to have you join this event, one that HNF is hoping to make an annual event. What makes this Summit so special is that the innovative content was developed in collaboration with numerous patient advocates, caregivers, clinicians, researchers, funding agencies and industry with one unified goal in mind...giving the patient a voice in discussing barriers and opportunities impacting their treatment.

You will have the chance to hear the latest in research developments, participate in panel discussions with clinicians, and voice your needs and priorities in regards to CMT research and treatments.

HNF believes that bringing all groups TOGETHER can influence research to be more patient-centered, useful, trustworthy, and ultimately lead to lifestyle guidelines and treatments for CMT/IN, making a difference in your life TODAY.

This Summit is BY patients and FOR patients. We NEED patients to participate and make this Summit a S-U-C-C-E-S-S!

A special thanks to this year’s Sponsors, Partners and Collaborators who allowed us the opportunity to provide scholarships, welcome bags, host meals and snack breaks, and share the outcomes from the Summit online: Acceleron Fearless Caregiver PenAgain Alter-G Inspire Pharnext Bombas Socks Invitae Pria Gonzales/Walmart CapTel MNG Labs Rare Disease Report CoolMess Neurology Reviews VirtuSense Technologies Dorothy J. Fairman Travel Scholarship Ortho Rehab Designs whatshouldwedo.com

Thank you to the Technical Planning Committee that helped shape the content, identify speakers and panelists, and develop a comprehensive program to share with you: Joy Aldrich Courtney Hollett Dr. Lucia Notterpek Matt Downing Debi Houliaris Dr. James Nussbaum Dr. Sean Ekins Elizabeth Katz Jessica Roberts Kristin Gelzinis Joy Kaye Tina Tockarshewsky Dr. Mark Gudesblatt Estela Lugo

So please join in, make new friends, create new collaborations, build new partnerships, but most importantly, Be Inspired!

On behalf of the entire Hereditary Neuropathy Foundation and Technical Planning Committee, we welcome you to the iconic New York City! We are glad you are able to attend.

Warm regards,

Allison Moore Founder and CEO Hereditary Neuropathy Foundation 2 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

Thursday, October 6, 2016

7:30am – 8:15am Continental Breakfast

8:15am – 8:30am Opening Remarks

8:30am – 9:00am Keynote Speaker: Culinary Nutritionist, Stefanie Sacks, M.S., C.N.S., C.D.N. and Author of What the Fork Are You Eating? “An Action Plan for Your Pantry and Plate” Navigating nourishment and learning how to cook CAN make a difference in how you feel—small changes in food choice can be part of YOUR prescription for healing.

9:00am – 9:20am Speaker: Kim Goodsell, CMT Patient, “The Patient of the Future: Patient as Expert, Health Maker, and Collaborator” How an extreme athlete uncovered her own genetic flaw. When Kim Goodsell discovered that she had two extremely rare genetic diseases, she taught herself genetics to help find out why.

9:25am – 10:00am Panel Discussion, Moderator, Lori Sames, Founder of Hannah’s Hope Fund, “Genotype and Phenotype: Managing Symptoms, The Role of Researchers/Clinicians” CMT has many different forms – each with different causes and symptoms. Lori Sames, “Fighter Mom” of a child with a form of IPN, champions gene therapy and shares how researchers and clinicians can help. Panelists: Joy Aldrich, David Walk, M.D., Chris Tan, M.S., L.C.G.C.

10:00am – 10:20am Break

10:20am – 11:00am Panel Discussion, Moderator, Tim Boyd, NORD’s Associate Director of State Policy and Advocacy “Public Policy” Better AFO (leg-bracing) options, fast-tracking drug discoveries and clinical trials, applying for disability benefits, Medicare/Medicaid and services you may be eligible for. These pose a real challenge to CMT/IPN patients. How can we empower one voice for change in the system? Panelists: Albert Xinliang Liu, Ph.D., John Maddox, Bernadette Scarduzio, and Mitchell Warner, C.P.O., Xinliang “Albert“ Liu, Ph.D.,

11:05am – 11:55am Speakers: Robert Burgess, Ph.D., Sean Ekins, M.Sc., Ph.D., DSc., Steven Gray, Ph.D., and Lucia Notterpek, Ph.D. “Research Presentations” Hear the latest from researchers on translational drug discovery, clinical trials and more!

12:00pm – 1:00pm Working Lunch, Moderator, Gary Barg, CMT patient and advocate, “The Fearless Caregiver: The Caregiver’s Voice Matters and the Role of the Caregiver in Patient-Driven Research” Survey results show that 39% of adults, that’s 90 million Americans, are caregivers. Let’s discuss reducing the caregiver’s stress, learning ways to communicate effectively with healthcare providers, and the caregiver’s role in clinical trials, and more. Panelists: Kerin Reilly, Marguerite Loucas, Erin Howard HNF-CURE.ORG 3

1:15pm – 2:00pm Panel Discussion, Moderator, Stefanie Sacks “Personalized Nutritional and Exercise Prescription for the CMT/IPN Patient” How many times have we heard, “Exercise, but don’t overdo it”? “Eat more protein and less veggies and fruits”? We’ll discuss what works best from actual CMT patients, and nutritional and exercise experts. Panelists: Brent Baker, Ph.D., A.T.C.; Jennifer Decker, Kristin Gelzinis, Estela Lugo, Chris Wodke

2:05pm – 2:40pm Panel Discussion, Moderator, James Nussbaum, P.T., Ph.D., S.C.S., E.M.T. “Gaps in Available Patient-Reported and Clinical Outcome Measures and Barriers to Therapy Development” Discussion about the importance of the accurate assessment of how a patient improves from a baseline measurement and new technology tools to be used by clinicians to quantify change. Panelists: Mark Gudesblatt, M.D., Kenneth Attie, M.D., David Scher, M.D., Glenn Pfeffer, M.D.

2:40pm – 3:00pm Break

3:00pm – 3:40pm Panel Discussion, Moderator, Florian P. Thomas, M.D., M.A., Ph.D., M.S.; Chairman, Neuroscience Institute, and Director, Hereditary Neuropathy Center, Hackensack University Medical Center, “The Squeaky Wheel Gets the Grease: The Art of Being a Successful Patient is to Know How to Get on Your Doctor’s Nerves and Feel Good About It”. The Chair of HNF Centers of Excellence speaks out on knowledge gaps among health care professionals, how to identify providers that are well versed in CMT, what patients should expect from their providers, and how they can advocate for themselves or loved ones. Panelists: Allison Moore, Debi Houliares, Brian Loew

3:45pm – 4:25pm Panel Discussion, Moderator, Tim Coté, M.D., M.P.H., C.E.O. Coté Orphan “Participating in a Clinical Trial: The Good, the Bad and the Benefits”

Now is an exciting time! Finally there are clinical trials for CMT, but what does that mean for you? You need to know the facts. Dr. Tim Coté explains why orphan drugs are special and how being a rare disease impacts your clinical trial. Panelists: Mario Saporta, M.D., Ph.D., M.B.A., Matthew Downing, René Goedkoop, M.D.

4:30pm – 5:00pm Speaker: Michael Sereda, M.D., Professor of Neurology and Group leader in the Department of Neurogenetics, Max Planck Institute (MPI) of Experimental Medicine, Göttingen, Germany “Translational Medicine in CMT: Update on Preclinical and Clinical Trials” Hear the latest on these exciting new potential treatments for CMT.

5:05pm – 5:25pm Speaker: Robert Moore, husband to Founder/CEO of HNF “The High-Arched Foot: This is the Beginning? The Disease Awareness Challenge” Robert knows all too well the ins and outs of CMT/IPN’s. Over 90% of patients with CMT have a high-arched foot. Can this be the solution to the awareness problem?

5:25pm – 5:30pm Closing Remarks

5:30pm – 7:30pm Poster Session & Evening Reception 4 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

PANELIST KEYNOTE SPEAKER Allison Moore, Founder Stefanie Sacks, M.S., and C.E.O. C.N.S., C.D.N.

Allison Moore founded Hereditary Neuropathy Foundation An Action Plan for Your Pantry and Plate in 2001 in an effort to improve the quality of life for people with Charcot-Marie-Tooth. She spearheaded the foundation 8:30am – 9:00am after a hospital mishap where she was treated with The Hereditary Neuropathy Foundation is proud and medications that exacerbated her CMT symptoms. Today privileged to introduce Stefanie Sacks, our keynote speaker she can not walk without AFOs and has severe muscle at the first Patient-Centered Charcot-Marie-Tooth Summit atrophy, bi-lateral foot drop and hand weakness and on October 6, 2016 in New York City. deformity. If only her doctors knew that certain drugs were contraindicated and can bring out symptoms in patients Stefanie Sacks, M.S., C.N.S., C.D.N. is a Culinary Nutritionist, with a family history of CMT. Her goal was to create a author, consultant, speaker and food firebrand! foundation that would lead to the development of treatments and a cure for CMT, and increase awareness so She has been studying food and healing for 30 years, has the world would recognize CMT as a household name. her Masters of Science in nutrition from Teachers College, Columbia University, is a Certified Nutrition Specialist, HNF has made great strides in building awareness and research Certified Dietitian Nutritionist and is a graduate of the funds for CMT, but Moore was not content to rest on this Natural Gourmet Institute for Health and Culinary Arts. success. This year, she decided it was time to create and lead an event dedicated to putting the CMT patient in the spotlight. Stefanie works hands-on with individuals and groups seeking a healthier way of eating. For companies and The first Patient-Centered Charcot-Marie-Tooth Summit is a organizations looking to do the right thing for their tremendous step in bringing global awareness among CMT consumers and environment, Stefanie is the go-to- gal—her patients, caregivers, researchers, health care professionals, unique background in food and agriculture as well as health funding agencies and industry. and wellness gives her the knowledge and skills to guide groups towards true food transparency, sustainability and Allison wanted to share this message for those attending ultimately health as a consultant, speaker and media expert. this landmark event: Her clients range from chefs and others in the industry— “My goal for EVERY patient coming to the Summit is to including Jean Georges Vongerichten and Chef’s Warehouse walk away with HOPE. Have hope for treatments. Hope that as well as Titan Tea, a food product company—as they aim a safe place to voice their concerns exists. Hope that HNF is to create a more transparent supply chain as well as bring here to help CMT patients and their families. Hope that HNF real nourishment to their offerings. She is also allied with is their voice and advocate for a better future. many consumer, health and environmental organizations I also want all stakeholders to feel confident that HNF is locally and globally offering her expertise to several backing their efforts, research initiatives, HCP education and including United Nations, A Greener World and awareness, and that we know the gaps and are actively Environmental Working Group. working to fill them. In addition, Stefanie was the co-starter of the very visible Each of us need to tell our story. CMT deserves attention NOW.” and successful #WhatTheFork petition at Change.org to HNF-CURE.ORG 5

push Whole Foods Market and Walmart to start selling ugly I went on a very specific diet for 2 months under her care fruits and vegetables thus addressing massive food waste in and after the first month I was able to go off every one of the United States. my five medications. My health and my perspectives about the impact food choice had on my health outcome became Her teaching experience is extensive. She is a preceptor for forever etched in my being. And I was determined to teach Columbia University’s Dietetic Internship program and was others what I had learned. an adjunct professor in the graduate nutrition program at the University of Bridgeport. Sacks also served as faculty at Fast forward 20 years, I became ill and unfortunately teams Kripalu Center for Yoga & Health as well as Food As of doctors were unable to properly diagnose me for almost Medicine, the universally acclaimed professional training 10 years. It was a very difficult period in my life and one program. She has also inspired many through workshops where I turned to all I had learned about food and health at Donna Karan’s Urban Zen Center, various resort spas, from my adolescent experiences to my formal culinary wellness centers, schools and universities around the country. training as well as my years at Teachers College, Columbia University while studying for my masters of science in Her book, What The Fork Are You Eating? An Action Plan nutrition education. for Your Pantry and Plate (Tarcher | Penguin Random House) provides an aisle-by- aisle rundown on how to shop I knew that I was doing all I could to keep myself healthy and cook healthier. She is a firm believer that small changes through food choice but that wasn’t enough. After two in food choice can make big differences and is a sought avoidable surgeries, I was finally diagnosed in 2010 with a after speaker, consultant and media guest expert on the renal disease (thought to be genetic) that affects how my topic of healthy choices, with frequent appearances on the kidneys regulate the pH of my blood (and caused a cascade Dr. Oz Show, PBS, Fox Media, and multiple radio programs. of symptoms, irreversible problems and challenges that impact my everyday). She also hosted her own radio show, Stirring the Pot, on Hamptons NPR, WPPB 88.3FM for three years. Her extensive In terms of my diet, quite coincidentally, because it had online and print contributions include The Huffington Post, been so healthy for some 25 years, it was more difficult for Alternet, Family Circle, Prevention, fortune.com, foxnews. the doctors to make a diagnosis because the disease com and foxbusiness.com. markers were inconsistent compared to a person eating a more processed foods diet. While my diet kept me so Sacks lives on the East End of Long Island with her husband, healthy for so long, it also made it more difficult for the two very active young boys and Blossom, the family dog. doctors to diagnose me!

Let’s learn more about her journey with nutrition, the five HNF: What has been the biggest food topic in the last things you’ll always find in her fridge, and what cooking 5 years? show star she would love to cook with. Stefanie: HNF: What inspired you to study food and how it The biggest food topic always seems to center around the impacts health? next best weight loss solution or super food. What actually takes center stage at any given moment tends to be about Stefanie: marketing dollars more than anything else. I suffered with terrible allergies, asthma, recurring bronchitis and pneumonia as a kid. Doctors kept drugging Despite this ongoing conundrum, consumers are surely me and I kept getting sicker. At the age of 15 (in the 1980’s) seeking healthier options and wanting more food I started working in local health food market and café as a transparency—a good thing. But we are a long way off in summer cook and it was there that I picked up Food & terms of people really understanding what authentically Healing by Annemarie Colbin, Ph.D. There began my healthy means. journey of connecting what I ate to how I felt. HNF: How have you seen nutrition impact those with I became my own guinea pig as I cleaned up my diet, chronic illness and disease? dabbled in many different dietary approaches from macrobiotics and vegetarianism to the blood type diet (to Stefanie: name a few). Ultimately, Dr. Sherry Rogers, an I revert back to my own experiences and see what changing environmental MD and author of Tired or Toxic, supported my food choices over the years has done to my own health. me in my quest to find health and wellness through a mixture of allergy shots, supplements and diet and lifestyle And professionally, I can only speak about what I see and I shifts in the late 80’s and early 90’s. can truthfully say that I have helped hundreds of people (if 6 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

not thousands), over the years, on navigating food choice HNF: What are your top three tips for teaching children to and shifting dietary patterns to support health. When make healthy food choices? committed and compliant with my suggestions (and those of some of my trusted colleagues), my clients, students, Stefanie: readers and listeners tend to see a great change in how 1. Get your Edible Education so you can talk to your they feel even with small changes like removing all foods children about food in the right way. containing artificial ingredients and of course more 2. Get them involved in everything food from shopping, complex ones like removing pro-inflammatory foods or to putting away groceries to cooking. following a specific “medical” diet. 3. Grow food in pots or plant a garden and let them take the lead here. HNF: What role can nutrition play for CMT patients and their caregivers? HNF: If you could be a guest on a cooking show, which one would it be? Stefanie: There is no research that I am aware of that focuses on CMT Stefanie: and food choice. However, Dr. Terry Wahls, an MD with I would love to cook alongside Rachel Ray. Her audience is multiple sclerosis (also a demyelinating disease) has done cross section that needs capturing and if I could challenge extensive research into the effects of the Paleolithic diet on Rachel to sprinkle a little authentic health conversation improving symptoms. (and ingredients)—in my What The Fork way—into her food then together we would have the chance to shift a I believe that educating CMT patients on how to navigate larger percentage of the population. healthy food choices (within the context of what they can and can’t do) as well as exploring a modified Paleolithic HNF: Name 5 things you will always find in your fridge. diet may be a good first step! Stefanie: HNF: What are the biggest challenges people face when 1. Avocados making food choices? 2. Cucumbers 3. Kale Stefanie: 4. Citrus (lemons & limes) Each person has different challenges—and that must be 5. Apples honored. However, if I were to choose an across the board challenge it would have to be that people think that they HNF: What do you hope attendees take away from need to change everything immediately. your keynote?

Shifting takes time, especially if needing and wanting it Stefanie: to last is a priority. Always know that small changes make I hope that attendees appreciate the true value food choice a big difference. My goal is to set people up for success, has—what and how we eat—on health outcome. not failure! We literally are what we eat (and we are what they ate and HNF: What is an “Edible Awakening?” how they were treated when it comes to animal foods). Eating healthfully does not have to break the bank. With Stefanie: the right education and commitment on your part, small Simply put, getting educated on how to make healthier changes are possible and will make a big difference. food choices. I like to think that my book, What The Fork Are You Eating, will give readers the Edible Education they You can read more about Stefanie and her mission on need to begin their Edible Awakening! her website www.stefaniesacks.com

HNF: What can each of us do right now to make a big difference in our health and wellness?

Stefanie: Make a commitment to yourself to get educated and pick up a copy of my book! From there you can choose one or two things to start shifting. For example, it may be that you will start by removing all food dye from your diet (whether in pickles, soft drinks or baked goods). HNF-CURE.ORG 7

reversed much of my disability. The success of my treatment strategy is dismissed as anecdotal. I actively advocate for the scientific legitimization and the embrace of anecdotal evidence.

At the epicenter of the medical community’s debate on the dangers and advantages of giving power to the people to direct and take control of their healthcare, I co-star with Angelina Jolie in the Medical Blockbuster Book Of The Year: “The Patient Will See You Now – The Future of Medicine is SPEAKER in Your Hands.” Kim Goodsell Defying the medical profession’s expectations of today’s “google and go“ patient, I have won international acclaim and high praise as a “unique”, “one-of-a-kind”, and The Patient of the Future: Patient as Expert, “extraordinary” patient. Health Maker, and Collaborator I reject this characterization. It’s socially disempowering, concealing an implicit suggestion that I am an outlier and 9:00am – 9:20am will continue to be. In my community, the rare disease Kim Goodsell is the patient of the future. community, greatness is commonplace. She is the expert. The maker. The collaborator. It’s the people living with rare disease, chronic disease, and In the years prior to her CMT diagnosis, Kim discovered disability that are pushing the edges, driving research, and she had another genetic disorder. She also has arrhythmo- health innovation from the bottom up. This is where you see genic right ventricular cardiomyopathy (ARVC), an inherited the future of healthcare. heart disorder. Greatness is not some rare DNA strand. We are ordinary Advocating for her own health, Kim was able to harness the people, hackers, artists, and activists. We are creating a future power of genetic information to devise a treatment plan that of #HealthMadeByUs. My husband, CB, and I are members of not only reduced, but reversed much of her disability with CMT. a growing alliance of DIY #HealthMakers. We have spent the better part of our 35 years together roving through remote Let’s learn more about her journey from her own words: It’s wildness perfecting the art of movement, engaged in what been over stated for sure, but my do-it-yourself diagnosis of some might consider extreme endurance activities. the confounding continuum of rare diseases I have: CMT — a disabling nerve disorder and ARVC — a rare life-threat- Today we are employing our art to restoring meaningful ening heart condition, has been said to mark an important mobility to our vulnerable disabled community who are watershed in medicine. disproportionally poor. We are makers of ROVA, an award winning walker and founders of ROVA RealTime, a young Dr. Eric Topol, one of the world’s foremost physicians and a California Benefit Corporation coming of age with the medical visionary, publicly characterizes me as “The Patient attitude that good design is a human right. of the Future.” I am deeply committed to exploiting my health odyssey to help catalyze medicine's “Gutenberg HNF: Why did you choose your particular topic for moment“ and the rise of the Patient of the Future: the the Summit? Expert, the Maker, the Collaborator. Kim: A UCSD college dropout, I earned an honorary Doctor of I am deeply committed to raising the patient expectations in Medicine degree, tuition free, from the infamous Google both the patient and medical community. We, as patients, University of Medicine. My googled research has been have excepted/expected things to be done “to“ us, or “for“ accepted for publication in the peer reviewed Journal of us, and not “with” us. Cardiovascular Electrophysiology. With great humility, I have found myself at center stage of the digital/genomic revolu- This attitude has been imposed through many millenniums tion in medicine, participating with its vanguards in the of a paternal patient/doctor relationship. Ubiquitous connec- co-production of medical intelligence. tivity, the online democratization of information, social media, the fury of hyper-innovative digital technology, and Harnessing the power of genetic information, I devised a consumer genomic sequencing are driving a radical shift in successful treatment plan that not only attenuated, but the power and organizational structure of medicine. 8 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

The empowered patient is precipitating the most profound living with these debilitating and sometimes fatal disorders revolution in the history of healthcare and it’s about are critical to developing the treatments and finding cures engaging human potential. This is truly a Renaissance in for these diseases. healthcare. The only obstacle is piercing the barrier of disbelief, that the patient is not capable of being the One of these rare genetic diseases is Giant Axonal Neu- “expert”, the “maker”, the “collaborator”. ropathy: an autosomal recessive genetic disorder caused by mutations on both copies of the GAN gene. The disease HNF: How has CMT affected your life? generally appears in early childhood, and progresses slowly as neuronal injury becomes more severe. Children with GAN Kim: don’t survive past their teens or twenties. It has unleashed an element of genius and helped me find my greatness. HNF has the honor of knowing one such GAN patient, Hannah Sames. She was diagnosed with GAN at four years HNF: What do you hope attendees take away from old, and now at age twelve, Hannah can no longer walk on the Summit? her own.

Kim: Her mom Lori Sames, and her husband Matt, formed I’d like leave you with a quote: Hannah’s Hope Fund (HHF) following Hannah’s diagnosis in “Somehow we’ve come to believe that greatness is a gift 2008. They work tirelessly to fulfill HHF’s mission: to raise reserved for a chosen few … for prodigies … for superstars and funds to support the development of treatments and a cure the rest of us can only stand by watching. You can forget that! for GAN, and be the resource for doctors, scientists, and Greatness is not some rare DNA strand … it’s not some precious families around the world. thing. Greatness is no more unique to us than breathing. We’re all capable of it … all of us!” Nike – The Jogger In 2012, Allison Moore met Lori at the World Orphan Drug Conference in Washington, D.C. When Allison met Lori, she We can’t wait to hear more about her journey and what it was drawn to her determination in learning the science takes to become a patient of the future! behind the rare disease affecting her daughter.

You can watch Kim’s video autobiography ROVA REAL Ever since that first meeting, these two “Fighter Moms” WARS: Episode 1 – Remembering the Future – YouTube – have joined forces, sharing their organizations’ mission, Part Alice in Wonderland, part Star Wars, part Monty researching business models, and the most effective Python, part Looney Tunes, part music video, 100% approaches to engaging industry, initiating collaborations, inspirational medical epic, 100% DIY. and most importantly, never taking no for an answer!

And all the hard work, networking, and fundraising is finally paying off for Hannah and her family.

Hannah is currently taking part in a clinical trial at the National Institute of Health in Maryland. She is the fifth child to take part in the clinical trial, which started in May of 2015. Hannah will stay at the National Institute of Health for 60 days following her injection.

SPEAKER/MODERATOR “We are so very happy today. The blueprint of Hannah's life changed today. The pages are blank and a new future is Lori Sames before her.” — Lori Sames According to Matt Sames, it takes about two years to Genotype and Phenotype: Managing Symp- realize full clinical benefit, but the four children who have toms, The Role of Researchers/Clinicians already received injections are doing well. The children are experiencing more leg strength and better breathing.

9:25am – 10:00am We look forward to hearing how this Fighter Mom is Raising global awareness of inherited neuropathies is a dai- bringing hope for children with GAN and their families. ly challenge we face head on at The Hereditary Neuropathy More About Lori: Foundation. Recognizing and understanding the people Lori Sames received a Bachelor’s degree in economics from HNF-CURE.ORG 9

St. Michael’s College, in VT, in 1992. She worked for IDX HNF: Why did you choose your particular topic for Systems Corporation as a computer software installation the Summit? consultant for healthcare until 1996. She then became a Joy: Senior Project Lead for integrated healthcare delivery I'm intrigued by the vast differences in how CMT affects system installations. different people in different ways, even within the same type of CMT. For example, my brother has hip dysplasia and Before becoming a stay at home mom in 2001, prior to the very arthritic-looking hands, while I have terrible feet/ birth of her second child, Reagan, she lead web-based ankles and have to wear AFOs to correct drop-foot. software installations on wireless networks, in the outpa- tient setting for Allscripts. She helped with her husband’s Most recently, I've become an advocate for getting word Pet Lodge businesses from time to time, while caring for out that CMT nerve damage can cause respiratory issues. her three daughters until her youngest daughter, Hannah, That makes CMT terminal and I hope this will further was diagnosed with GAN in March of 2008. motivate researchers, clinicians, and industry to find treatments or a cure for this awful disease. From that moment forward her life has been dedicated to finding treatments and an eventual cure of GAN, and HNF: How has CMT affected your life? making lasting memories for her family. Joy: Growing up, it was just something I had to deal with and make excuses for. I never told anyone about my CMT until I was 43 when I had to start wearing AFOs. I had to use a scooter to get around Disneyland when we took my nieces there two years ago, and it was really hard for me to let them see me like that. Recently, my mom passed away due to respiratory failure secondary to CMT1A and I really miss her!

PANELIST On a positive note, CMT has lead me to HNF, and an amazing community of people who GET it. I truly feel empowered by the work that I do for HNF and this Summit, Joy Aldrich and by helping people deal with CMT issues in the Inspire online support and discussion community. Joy Aldrich, CMT Advocacy Director, joined HNF in February HNF: What do you hope attendees take away from 2015 to focus on the growth of HNF’s online patient support the Summit? community. Joy and her husband, Toby, live in Seattle, WA, with their beloved yellow lab, Charley, and adopted choco- Joy: late lab, Tobydog (he came with that name!). While food Empowerment! I hope that CMT patients walk away from service distribution was her career, finding a treatment for the Summit feeling stronger, more informed, and ready to CMT, traveling, and cooking are her passions. You may advocate for themselves and CMT. I hope they'll get remember her food blog, www.apassionateplate.com. involved in the Inspire community, HNF Facebook, GRIN, CMTConnect, and Centers of Excellence. I hope researchers, Joy was diagnosed with CMT as a teenager, after years of clinicians, and industry participants will walk away knowing trips, falls, and sprained ankles. Her mom and brother how CMT affects lives. After meeting patients face to face were also diagnosed with CMT at that time. Years went by and hearing about their challenges, I hope they will be before Joy noticed the more rapid progression of CMT even more motivated to find a treatment or cure for CMT. symptoms and pursued a genetic diagnosis, which was confirmed as CMT1A. Be sure to connect with Joy in HNF’s Inspire Community here: https://www.inspire.com After her genetic diagnosis, Joy connected with HNF for advice on AFOs and a letter writing campaign to tell family and friends about her diagnosis. Since then, Joy has participated in HNF’s CMT Awareness month video cam- paign, hosted fundraisers in the Seattle area, moderated the Inspire CMT online support and discussion community, and helped plan and organize this Summit. 10 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

pediatric, newborn screening, and specialty (neurogenetics and ophthalmology) clinics at the University of Chicago;and was a senior genetic counselor at an academic molecular diagnostic laboratory specializing in neurological disorders. He is currently a Clinical Instructor in the Department of Medical Genetics at the University of British Columbia.

He is an active member of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic PANELIST Counsellors. Chris holds a Master of Science in Human Genetics from Sarah Lawrence College and a Bachelor of David Walk, M.D. Science in Biochemistry from the University of Waterloo.

David Walk, M.D. trained in neurology at the University of Chicago and has been at the University of Minnesota since 1999. His current clinical and research areas of focus are neuropathy, particularly small fiber neuropathy and CMT, and ALS.

He directs the University of Minnesota Health CMT multidis- ciplinary clinic. The University of Minnesota Health CMT clinic was recently named an HNF Center of Excellence. In addition, they are currently accepting patients for the SPEAKER/MODERATOR Pharnext Phase 3 clinical trial of its lead pleodrug PXT3003 in Charcot-Marie-Tooth Disease Type 1A (CMT1A). Tim Boyd Dr. Walk is especially interested in the value of the multidisci- plinary team approach to helping people living with CMT Public Policy and is excited about the emerging opportunities to advance care utilizing our expanding tools in neuromuscular genetics. 10:20am – 11:00am The availability of affordable healthcare is an issue that affects each and every one of us. This is even more critical for patients with rare diseases.

HNF has partnered with NORD to help us find the solutions and realize a brighter future for those living with CMT and other INs.

According to Tim, the cost and availability of health care services for patients with a rare disease are dependent PANELIST upon state-based policy decisions. The design of public and privately-funded health care plans does not always take the Chris Tan, M.S., L.C.G.C. needs of the rare disease community into account in determining benefits and costs.

Adding a genetic counselor to your team of healthcare Tim has served as NORD’s Associate Director of State professionals can be a great benefit for CMT patients and Policy and Advocacy since 2015, and is responsible for their their caregivers. Genetic counselors evaluate and under- policy activity in all 50 states. Prior to that, he worked on stand a family’s risk of an inherited disease. They have federal and state public policy for eight years with the specialized training in medical genetics and counseling that AIDS Healthcare Foundation (AHF). Tim earned his B.A. can help you understand and adapt to the medical, psycho- in Political Science from the University of California Santa logical, and familial implications of genetic diseases. Barbara and is an M.P.H. Candidate (2017) at George Washington University Milken Institute of Public Health. Chris is the lead neurology genetic counselor at Invitae. Chris previously provided genetic counseling in prenatal, general His goal for the Summit is to provide attendees with a sense HNF-CURE.ORG 11

of NORD’s perspective on state-based health care issues affected by this condition. I look forward to learning more and inform them about ways they can engage with us on about this disease and the research needs of the CMT various initiatives. community at the Summit.

You can connect with Tim here: www.raredisease.org HNF: What do you hope attendees take away from the Summit?

Dr. Liu: I hope that patients can realize that they are not alone. There are collaborative efforts to help them enjoy their lives while living with the disease.

HNF: Anything else you’d like to share with the community?

Dr. Liu: PANELIST I genuinely hope to learn more about patients with CMT: how current treatment options work for them, how they Xinliang “Albert” Liu, Ph.D. can find insurance coverage for their care, what issues they encounter in the health delivery system, and so on. Such conversations will help me find opportunities to design Xinliang “Albert” Liu, Ph.D, is an assistant professor in the research studies that improve their care experiences. Department of Health Management and Informatics at the University of Central Florida. His research focuses on health services utilization, costs, quality of care, and performance evaluation of healthcare organizations. Dr. Liu’s research expertise includes the development of novel methodologi- cal approaches for clinical and policy issues such as the impact of different treatment patterns, medical complica- tions, and effectiveness of interventions in real world settings. Dr. Liu received an MD-equivalent degree from China and a PhD degree in health services research from Virginia Commonwealth University. PANELIST Dr. Liu shares the consensus that CMT is a lesser known disease and more research is needed to shed light on the John J. Maddox experiences of patients with CMT. He will discuss how to fill the information gap to better serve the CMT community at John is Founder and Managing Director of Infusion Pharma the Summit. He will also present a poster that examines the Consulting LLC, a leading business strategy consultancy acute hospital care used by patients with CMT in Florida. focused on the Orphan Drug and Hospital Therapeutics. HNF: Why did you choose your particular topic for Founded in 2003, the company serves clients worldwide the Summit? ranging from start-ups to Top 5 companies.

Dr. Liu: John has extensive industry experience, gained primarily Little systematic research exists regarding the care utiliza- with Novartis, which includes senior level responsibility for tion, costs, and quality of care among patients with CMT. For business unit management, commercial research, M&A, and example, we don’t know the economic burden of CMT and corporate strategy. He holds an M.B.A. from the Wharton such information is needed for health planning and care School and a B.S. in Pharmacy from Rutgers. He interned at improvement. I am passionate about using my knowledge Lenox Hill Hospital in Manhattan. and research expertise to serve the CMT patient population. His professional interests include business models that HNF: How has CMT affected your life? balance patient access with continued new product research, healthcare policy and market strategies for Dr. Liu: pioneering products. Although I don’t have CMT in my family, I am getting to know more and more individuals whose lives have been 12 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

HNF: How do you manage your CMT symptoms?

Bernadette: My CMT is progressing, but I keep on fighting it with pool therapy, land therapy, meditation, a good laugh, amazing family and friends, and my 2 dogs, Sadie and Puppy.

HNF: What do you hope attendees take away from the Summit?

PANELIST Bernadette: I'm looking forward to sharing my experience with CMT, Bernadette Scarduzio alternative medical therapies, Medicare/Medicaid assistance, and living life to the fullest despite an illness.

My name is Bernadette Scarduzio and I'm a CMT patient HNF: Anything else you’d like to share with the community? and advocate! I reside in Drexel Hill, PA with my 2 dogs. Bernadette: I'm proud to say I’ve been working for the Hereditary Thank you all for the constant support! Neuropathy Foundation for almost 3 years now. I started out as a volunteer for HNF, joining the fight to raising Want to connect with Bernadette? You can find her here: awareness and funds for CMT. www.bernslife.wordpress.com www.BernadetteCMTmovie.com Some may recognize me from the documentary “Bernadette” that was released in 2013. HNF helped fund the film and still features it on their website for anyone who would like to purchase it.

Making that documentary, which was started in 2008, really helped me get the word out on CMT and what it's like living with a progressive illness that has little to no awareness and support. Growing up with CMT was very hard because no one knew what it was, not even doctors! I had to do a lot of explaining to countless PANELIST medical professionals to get the care and treatment I needed. Mitchell Warner, C.P.O. Filming the documentary wasn’t easy, but my goal was to help others so they wouldn't have to go through Bracing is used in the management of Charcot-Marie-Tooth all I endured. to support and hold a part of the body compromised by HNF: Why did you choose to participate in the Summit? muscle weakness, muscular atrophy, and/or sensory impair- ment. Bracing is also used to help correct skeletal deformity. Bernadette: Participating and being one of the panelists on the There are a variety of braces available for ankles, knees, discussion of Public Policy at the Summit means the world feet, hands, and other areas affected by CMT. For CMT to me. Not only do I get to meet others who have CMT, patients, bracing can help regain the ability to walk quickly but I also get to meet with the doctors, scientists, and smoothly, and provide greater independence in nutritionists, and many others who are all trying to help everyday activities. us with CMT. HNF has invited Mitchell Warner, C.P.O., of Ortho Rehab I've always felt awareness is our key to a cure. My next Designs Prosthetics and Orthotics, Inc., to join us at the big goal is to be on “Ellen”. Not only is she an inspiration Summit on the panel discussion Public Policy. Mitchell to me, but she makes me laugh and helped me accept Warner graduated from the New York University Post being gay and disabled. I would love to thank her in Graduate Medical School's program in Orthotics and person one day. Prosthetics, and is American Board Certified in both prosthetics and orthotics. HNF-CURE.ORG 13

Established in 1991, Ortho Rehab Designs is nationally recognized for the HELIOS® Orthotic System. The Helios® orthosis is a custom energy loading graphite composite brace. Easy to put on and take off, the unique design is an incremental improvement over existing bracing systems. It uses Triplanar control to correct and stabilize the joints of the foot and ankle.

HNF: Why did you choose your particular topic for the Summit? SPEAKER Mitch: It is a priority to get insurance carriers to pay for custom Robert Burgess, Ph.D. energy storing leg braces. These devices help restore balance, help correct deformities of the joints, and can lead Research Presentations to an increased walking speed.

HNF: How has CMT affected your life? 11:05am – 11:55am We are fortunate to have the leading CMT researchers Mitch: share their latest progress at the Summit. HNF has invited Working predominantly with CMT patients, it has led me to Dr. Robert Burgess, a member of our scientific advisory design innovations in leg bracing to help CMT patients walk board, to present his latest research. better and have greater balance. Dr. Robert Burgess is a Professor at The Jackson Laboratory HNF: What do you hope attendees take away from in Bar Harbor, Maine, where he has directed a research the Summit? group since 2001. Dr. Burgess received his B.S. in Mitch: Biochemistry from Michigan State University, his Ph.D. I hope attendees learn what custom made corrective leg in Neuroscience from Stanford University, and was a bracing can provide as a medical treatment, to give a postdoctoral fellow at Washington University, St. Louis better quality of life, and to prevent further breakdown prior to joining Jackson Labs. of the joints. A major focus of the Burgess lab is developing mouse HNF: Anything else you’d like to share with the community? models of inherited peripheral neuropathies using genome editing techniques. These animal models are then used to Mitch: better understand disease mechanisms and for preclinical These innovations that I have made for CMT patients to testing of therapeutic approaches. This research is funded walk better has led me to design a leg brace for my own by several agencies including the National Institutes of medical condition using new design applications. Health and the Muscular Dystrophy Association.

You can learn more about Mitch and how the HELIOS® Dr. Burgess is on the scientific advisory board of the Orthotic System can help CMT patients here: Hereditary Neuropathy Foundation, and also serves on Website: www.HeliosBracing.com the Cellular and Molecular Biology of Neurodegeneration Email: [email protected] grant review panel for the National Institutes of Health. Phone: 888-696- 9909 Dr. Burgess is married with two (nearly) grown children, and enjoys living next door to Acadia National Park.

HNF: Why did you choose to present your research at the Summit?

Dr. Burgess: I am a CMT researcher, but what started as a scientific interest has grown as I have integrated into the CMT research community and become more involved with patients and advocacy groups such as the HNF.

HNF: How has CMT affected your life? 14 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

Dr. Burgess: Pharmaceuticals Inc. (now Vitae Pharmaceuticals Inc), and I now appreciate this is an important but often overlooked Vice President of Computational Biology at GeneGo (now condition, with a growing and dedicated community Thomson Reuters). seeking a cure. Dr. Ekins is Adjunct Professor, Division of Chemical Biology HNF: What do you hope attendees take away from and Medicinal Chemistry, UNC Eshelman School of Phar- the Summit? macy, University of North Carolina at Chapel Hill, Adjunct Associate Professor, School of Pharmacy Department of Dr. Burgess: Pharmaceutical Sciences, University of Maryland, and I hope that patients will take away that there is a focused Adjunct Professor in the Department of Pharmacology at research effort trying to develop treatments for CMT. Rutgers University– Robert Wood Johnson Medical School, While more effort and involvement would always be Piscataway, NJ. welcome, the real challenge is the underlying biology. These are difficult diseases to treat and we do not have a He has authored or co-authored over 270 peer reviewed well-trodden path to follow in terms of developing papers and book chapters, as well as edited four books and therapies. Progress is being made and many people are a book series on technologies for the pharmaceutical truly dedicated to this problem. industry. He has been awarded eleven NIH grants as a primary investigator.

Dr. Ekins is interested in the application of computational approaches to big and small data for rare and neglected disease drug discovery. His hobbies include cycling and hunting for records.

HNF: What should attendees know about CMT research today?

Dr. Ekins: SPEAKER As the CSO of HNF, I think it’s important to highlight what Sean Ekins, M.Sc., Ph.D., D.Sc. we are doing to fund science on this rare disease. HNF: How has CMT affected your life?

Research Presentations Dr. Ekins: I have a better appreciation for those living with the 11:05am – 11:55am disease as I interact with them. Leaders in Charcot-Marie-Tooth research need to be HNF: What do you hope attendees take away from progressive visionaries, willing and able to push the the Summit? boundaries to explore every opportunity available to advance therapeutics and clinical trials for CMT. Dr. Ekins: I hope attendees see that we are hopefully at a turning HNF has the great honor to have Dr. Sean Ekins lead our point with so much great academic science and so many research operations as our Chief Scientific Officer. companies actively working on treatments. The Summit will provide the big picture view of what is going on. Dr. Ekins is the co-founder and CEO at Phoenix Nest, a company focused on Sanfilippo Syndrome rare disease drug HNF: Anything else you’d like to share with the discovery. He is also the founder and CEO at Collaborations community? Pharmaceuticals, Inc., which is focused on rare and infectious diseases. Dr. Ekins: I look forward to personally meeting as many of you He graduated from the University of Aberdeen, receiving as possible! his M.Sc., Ph.D. and D.Sc. in Clinical Pharmacology. He was a postdoctoral fellow at Lilly Research Laboratories. He has Want to connect with Dr.Ekins? You can find him here: worked as a senior scientist at Pfizer, Lilly, Associate Website www.collaborations.com/CHEMISTRY.HTM Director of Computational Drug Discovery at Concurrent HNF-CURE.ORG 15

SPEAKER SPEAKER Steven Gray, Ph.D. Lucia Notterpek, Ph.D.

Research Presentations Research Presentations

11:05am – 11:55am 11:05am – 11:55am Dr. Steven J. Gray is an Assistant Professor in the Depart- Dr. Lucia Notterpek is a HNF Scientific Advisory Board ment of Ophthalmology, U. of N. Carolina at Chapel Hill. member. She received her B.A. in Anatomy-Physiology from He is also an investigator in the UNC Gene Therapy Center the University of California at Berkeley. She obtained her and Carolina Institute for Developmental Disabilities. Ph.D. in Neuroscience at the University of California at Los Dr. Gray was previously a Post Doc at UNC and before Angeles working with Dr. Leonard H. Rome. Her that had undertaken a Ph.D. in Molecular Biology, at postdoctoral training was under the guidance of Dr. Eric Vanderbilt University. Shooter at Stanford University. Currently, Dr. Notterpek is Professor and Chair in the Department of Neuroscience in His core expertise is in AAV gene therapy vector the McKnight Brain Institute at the University of Florida. engineering, followed by optimizing approaches to deliver a gene to the nervous system or eye. His major focus is in Dr. Notterpek investigates how the loss of glial insulation AAV vector development, creating vectors tailored to serve around axons, called myelin, contributes to the pathogen- specific clinical and research applications involving the esis of hereditary and age-related neural disorders. She nervous system. These include the development of novel studies diseases that are specifically linked with defects in AAV capsids amenable to widespread CNS gene transfer or myelin including peripheral neuropathies, such as CMT and specialized ocular gene transfer. multiple sclerosis.

As AAV-based platform gene transfer technologies have A major effort of Dr. Notterpek’s lab focuses on approaches been developed to achieve global, efficient, and in some to maintain healthy myelin during lifespan and/or restore it cases cell-type specific CNS gene delivery, his research focus in disease paradigms. The laboratory is equipped with has also included preclinical studies to apply these reagents models and reagents, including small molecule therapeutics toward the development of treatments for neurological and genetic models to attain these goals. diseases. Currently, these include preclinical studies for Rett Syndrome, Giant Axonal Neuropathy (GAN), Tay-Sachs, Other areas of active investigation include the optimization Krabbe, AGU, and Batten Disease, and have expanded into of lipid nanoparticles as therapy delivery vehicles for human clinical studies to test a gene therapy approach for neural disorders. GAN. He has published over 40 peer reviewed papers and Dr. Notterpek is the recipient of the 2004 Jordi Folch-Pi has 3 pending patents. His research is funded by NIH and Memorial Award from the American Society of Neurochem- other research foundations. istry, awarded to a young scientist for research excellence. She has authored and co-authored over 65 publications, reviews, and book chapters.

She is actively involved in the educational and research missions of the College of Medicine at the University of Florida. Her research efforts have been supported by the NIH, the National Muscular Dystrophy Association, the 16 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

National Multiple Sclerosis Society, the Facial Pain Foundation, and the Hereditary Neuropathy Foundation.

HNF: Why did you choose to participate in the Summit?

Dr. Notterpek: I want to share my knowledge and experience from working in basic translational laboratory research with the CMT patient population. Educating the public about the importance as well as the limitations of basic laboratory SPEAKER/MODERATOR research is of high significance.

HNF: How has CMT affected your life? Gary Barg Dr. Notterpek: The Fearless Caregiver: The Caregiver’s Voice I do not have CMT in my family, but I know people with the disease. Learning about the burden of the disease on the Matters and the Role of the Caregiver in patients and their families had a major impact on my career Patient-Driven Research decision, which has been committed to research on CMT for over 20 years. 12:00pm – 1:00pm

HNF: What do you hope attendees take away from Those caring for patients living with CMT are invaluable the Summit? members of our community. Caregivers are on the frontlines every day, helping patients manage their daily struggles and Dr. Notterpek: challenges of living with CMT. We will all gain new knowledge from different perspectives on issues related to CMT. I hope we will be even more These selfless people need to be recognized for their commit- energized in working together across the patient, the ment and dedication, and deserve their own advocacy caretaker, and research communities in our efforts to platform and a strong, influential voice to represent them. alleviate the burden of CMT. That undeniable voice for the caregiver is Gary Barg. HNF: Anything else you’d like to share with the community? Noted speaker, author, and publisher on caregiving issues Dr. Notterpek: since 1995, Gary Barg is the CEO and Editor-In-Chief Care- I highly value my interactions with the patient population. giver Media Group, and Founder and Editor-In-Chief of the Learning about the specifics of the disease from patients first national magazine for caregivers, Today’s Caregiver. He impacts my thinking in experimental design as well as in is also credited with creating the original online caregiver data interpretation. community, caregiver.com. But he didn’t stop there! Gary created The Fearless Caregiver Conference, uniting caregivers across the world to share their knowledge, experience, and priceless wisdom. He is a published author of two books, “The Fearless Caregiver” and “Caregiving Ties That Bind.”

His many accomplishments and awards has earned Gary the spotlight, interviewing with highly recognized media outlets such as The Today Show, Bloomberg Radio Network, Time Magazine, The Wall Street Journal, and USAToday.

Gary has been a keynote speaker for many events across the U.S including: • The Huntington’s Disease Society of America • Massachusetts Multiple Sclerosis Society • The Sharing Wisdom Conference with Leeza Gibbons • World Congress on Disabilities • Living Longer/Living Better Conference HNF-CURE.ORG 17

And Gary has Charcot-Marie-Tooth. American Academy of Dramatic Arts, New York Campus. She is responsible for the management of the New York HNF: Why did you choose your particular topic for Admissions Department. She previously served as Director the Summit? of Admissions for the Adult Degree Completion program at Mount Saint Mary College. In addition, Kerin was an Gary: Adjunct Professor responsible for teaching Public Speaking I think it’s very important to discuss all partners within in both the hybrid online format and traditionally at the patient centered research outcomes, and that includes the Mount Saint Mary College’s military satellite campuses interaction between caregivers and loved ones. which are located at West Point and Stewart Air Force Base. HNF: How has CMT affected your life? She holds a Master’s Degree in Business Management and Gary: Administration. Kerin joined the HNF Board of Directors in CMT affects my life the more I age. I’m much more conscious 2014 to build awareness and contribute to advancing of taking care of myself, and getting as much exercise as I research for CMT. Her beautiful, brave daughter, Dakota am capable of handling. has CMT. Kerin’s intentions are to do everything in her capacity to help her daughter and all those living with CMT. HNF: What do you hope attendees take away from Kerin resides in New York and is married with two children. the Summit? HNF: Why did you choose your particular topic for Gary: the Summit? Learn all you can from the experts and providers who are all dedicated to supporting people living with CMT/IN. Above Kerin: all, we should take the time to learn from one another. As a mother, there is nothing more important to me than finding a cure for CMT. My daughter Dakota is a brave, HNF: Anything else you’d like to share with the community? kind, beautiful soul. She was diagnosed at the age of eleven and at that time, the focus of our lives became Gary: about finding the resources and connections to help Dakota You are not alone. Stay involved and don’t isolate as much as we possibly could. yourselves, for the sake of what you can learn from others living with CMT/IN, as well as what you can teach. As all patients and caregivers know, it is difficult to find health care professionals who are aware and educated on Want to learn more about Gary or have a question for him? this disease and many times, you find yourself educating Website: www.caregiver.com the individuals that you seek treatment from. It took many years, but we have managed to make connections with a physician, physical therapist, chiropractor, surgeon, and even a weight trainer.

It truly takes a trusted team of educated professionals, knowledgable about the effects of CMT, to provide Dakota with services that she needs to keep her safe from injury.

HNF: What do you hope attendees take away from the Summit? PANELIST Kerin: I hope that attendees of the Summit make valuable connec- Kerin Reilly tions and gain resources that can substantially help themselves and their families. Simply being in the presence of other Caregivers play a critical role in helping CMT patients caregivers and patients will provide a comfort in sharing manage the daily struggles and challenges of living with similar struggles and providing ideas and information that can this debilitating disease. They are a significant part of our grow into a support network for all of us fighting for a cure! community and we will be discussing the role of the You can connect with Kerin here: caregiver at the Summit. Kerin Reilly sits on the HNF Board LinkedIn: http://bit.ly/2duOsnO and is caregiver to daughter, Dakota, who has CMT. Facebook: http://bit.ly/2cE9Ipp Kerin Reilly is currently the Director of Admissions for The [email protected] 18 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

Marguerite: I just want to say how proud and grateful I am to have Allison in my life. I am continually inspired by her incredible strength of character and her drive to help all of those living with CMT.

PANELIST Erin Howard PANELIST Erin has been teaching customers how to use the CapTel Captioned Telephones for over three years. She travels around Marguerite Loucas the state, giving presentations and seminars to educate people about the free captioning service. Erin, who grew up Marguerite Loucas resides in New York City with her in Gramercy Park in New York City, brings a genuine enthusi- husband and three children. Her family owns the popular asm and positive approach to her work with customers. Best burger chain in New York City “Burger Heaven”. Seven part of the job? “It’s definitely seeing the joy and happiness I months ago she opened a make-your-own ice cream place bring to our customers when they find out for themselves called “CoolMess”. She is set to open her 2nd location in they can once again be independent and talk on the phone.” Roslyn, New York. Erin is excited to unveil this free service to the CMT patient community that is affected by the loss of hearing. When you see the definition caregiver in the dictionary one would not be surprised to see Marguerite Loucas.

She is an exemplary caregiver for individuals in her life that are challenged with a chronic illness. She happens to be best childhood friends with HNF’s CEO Allison Moore.

HNF: Why did you choose your particular topic for the Summit? MODERATOR Marguerite: Being a caregiver is something I don’t really think about. It’s in my heart. I cared for my mother as she struggled with Stefanie Sacks Alzheimer’s. I’ve been by Allison’s side for over 40 years and couldn’t imagine not caring for someone so dear to me. Personalized Nutritional and Exercise Prescription for the CMT/IPN Patients HNF: How has CMT affected your life? Marguerite: 1:15pm - 2:00pm I have traveled with Allison all over the world, so I’m aware of the struggles and challenges she faces while traveling. Over the years, I’ve learned the best ways to travel is to accommodate to her unique needs as a CMT patient.

HNF: What do you hope attendees take away from the Summit? Marguerite: I hope everyone leaves the Summit with more patience and awareness. We need to recognize that we’re making great PANELIST progress in developing CMT treatments and closer to finding a cure every day. This Summit will help the CMT community Brent A. Baker, Ph.D., A.T.C. continue to make great strides in spreading awareness locally and globally. Dr. Baker’s research and team has focused on quantifying and HNF: Anything else you’d like to share with the community? characterizing exposure-response outcomes and relationships HNF-CURE.ORG 19

with regards to soft-tissue (including but not limited to and mountain climber not only accomplished her goal, she muscle, vasculature, nerve, etc.) non-injurious and injurious also raised over $10,000 towards CMT research! physical loading as well as prevention/intervention-based adaptive approaches (i.e. “resistance-type” exercise). Impor- Let’s learn more about Jenny in her own words: tantly, the affects aging contributes to and interacts with I’m a Registered Nurse with over 10 years of experience, these factors is an overarching research focal area within the specializing in Medical, Neurological, Surgical, and Trauma lab. Further, our fundamental in vivo models approach is both ICU. I’ve been a traveling RN for the past 4 years. multi-disciplinary and integrative, in that we use a systems approach to investigate function at both the biomechanical Throughout my life I’ve tried to put my diagnosis of CMT (performance of the system) and physiological (molecular to behind me. “Out of sight, out of mind” right? I am just morphological) levels to identify and analyze etiology. Jenny: swimmer, hiker, surfer, scuba diver, kayaker, and lover of any adventure placed in my path. The resulting contributions from these works have signifi- cantly broadened the scientific understanding of soft-tissue Allowing my diagnosis precedence in my life was like adaptability with aging, exercise, and injury. The team’s granting it too much power. I was afraid if I did, it would ultimate objective is to translate these evidence-based overcome me, or even worse....break me. I have always findings into practice, so to improve the overall quality of been slower, clumsier, weaker, and more prone to injuries life and “healthspan” for all aging populations by identify- than everyone else, so why would acknowledging this ing how to limit age-related diseases, disorders, and injury. disease change these facts?

With respect to CMT, Dr. Baker’s team has collaborated Recently, my thoughts on living with CMT have changed. with Drs. Michael Sereda and Klaus Nave of the Max Planck My partner, Krystal Sentz, has played a major role in this. Institute for Experimental Medicine (MPI) to utilize their She always has a way of reaching for my hand on unsteady CMT1A transgenic rat and established the initial CMT1A rat ground without making me feel helpless. colony in the United States. Specifically, the lab is continuing to examine the effects of an initial investigation that implement- Together, we realized that this disease has actually ed validated, “resistance-type” exercise with these CMT1A rats empowered my entire life. It has been the foundation to by training them on a specialized machine, called a dynamom- my internal drive. It has been the fuel that allowed me to eter (i.e. similar to therapeutic/laboratory isokinetic equipment conquer things deemed impossible. These challenges have – Cybex, Kincom, etc.). Initial funding for this project was pushed me to find my own “ways” that work and allowed supported by the Hereditary Neuropathy Foundation. me to accomplish any goal I put my mind to.

My days as a “loner CMTer” came to an end when I decided to attempt the first solo circumnavigation by kayak around the Big Island of Hawaii. This was my chance to give to the CMT community and create awareness. A majority of close friends, family members, and medical co­workers have rarely even heard of this disease. The lack of awareness in the general public must be astronomical if those in my own life, a person with CMT, are unaware of it. PANELIST On March 25th, 2016, I pushed offshore on my kayak for a 20 day, 300+ mile, wild adventure through the Pacific Jennifer Decker Ocean. I completed my journey on April 13th, 2016 for every single person dealing with CMT. I was able to raise We met Jennifer Decker this past spring when she reached out over $10,000 towards further CMT research, created a to HNF about an incredible journey she was about to embark on. community between other CMT patients on the island, and brought media awareness to our disease. Jenny set out to complete the first documented solo circumnavigation of the Big Island, Hawaii by kayak. The HNF: Why did you choose this particular topic for the Summit? journey would take 20 days and course through over 300 miles of the roughest waters known in the Pacific Ocean. Jenny: I have been a competitive swimmer my entire life and And she would do it as a Charcot-Marie-Tooth patient. believe this has been one of the major factors in being able This experienced nurse, seasoned surfer, hiker, scuba diver, to remain so active, despite my CMT symptoms. 20 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

Furthermore, being more graceful in the water than on Bachelors in Psychology and Masters in Social Work, and land has always been a major incentive. In my personal ex- hold my license in clinical social work after working in EMS perience, finding low impact, muscle strengthening exercise for nearly ten years. I was initially in nursing school until a is key to minimizing injuries, slowing the progression of the doctor informed me that my CMT diagnosis would prevent disease, and maintaining muscle. me from being on my feet all day.

HNF: How has CMT affected your life? I started out depending on a wheelchair to get around. My legs were weak, my bones were deteriorating, and I was Jenny: listening to my doctors making sure I didn't fall or hurt CMT has empowered my entire life. I choose to say I’m myself further. “living with” CMT. This mindset allows me to see CMT as a blessing. I’m grateful for every day I can experience life on After years of complying, I decided to start listening to my body my own terms. instead. I started out slow, taking short walks with my son and kept pushing myself to do something a little more, go a little HNF: What do you hope attendees take away from further. I tried wheelchair softball, kayaking, and swimming the Summit? since my arms were still relatively unaffected by the disease.

Jenny: I started taking my son to more places and as his face This patient-focused Summit will bring hope to all of us lit up, it pushed me to continue to do more. I took him suffering with CMT and I am grateful to connect with the on bike rides, joined martial arts, and began advocating community at such an amazing event! for others with disabilities. Currently, I work with children with disabilities as well as adults diagnosed with mental HNF: Anything else you’d like to share with the community? health disorders. Jenny: I am an administrator for Facebook groups ‘CMT Stand By Remember, there is always a light in the dark. Sometimes Me’ and ‘CMTartists.’ We currently have over 1000 members you may have to go find it or you might just have to create from all over the world involved in our groups. We have also your own! started CMT-Connect, which a wellness/support group for Embrace your imperfections and no matter what your chal- those who have CMT and their caregivers in New York City, lenges are you truly can do anything you put your mind to! Long Island, and Rochester. I've been co-moderating the workshops on LI.

HNF: Why did you choose your particular topic for the Summit?

Kristin: I chose my topic because I strongly believe that I would still be in a wheelchair if I didn’t push myself to be more physically active. My activity level isn’t for every CMT patient. I understand CMT is a progressive disease. But sometimes we have to get out of our comfort zones to see what we are still capable of. PANELIST HNF: How has CMT affected your life?

Kristin Gelzinis Kristin: It’s always been a struggle to maintain balance in my life: The strength of the CMT community depends on the the constant changes with the progression of CMT and my unwavering commitment of its members. From patients, to drive to do more for my family and the CMT community. I caregivers, to researchers and HCPs, we are all in this will be able to bring a unique perspective to the discussion together to help raise awareness and funds to develop as a patient who’s been there. treatments and find a cure. HNF: What are you most looking forward to at Let’s hear more about Kristin in her own words: the Summit?

It’s taken me a long time to get where I am today from Kristin: when I was initially diagnosed with CMT. I have my I can't wait to connect with others during the Summit. HNF-CURE.ORG 21

I'm interested in listening to their stories and excited to HNF: What do you hope attendees take away from share mine. I'm curious about the latest CMT research and the Summit? look forward to having all of our voices heard by the professionals. Estela: I hope they leave the Summit feeling empowered from the educational presentations, inspired by the success stories, and connected to the new people they meet.

HNF: Anything else you’d like to share with the community?

Estela: This will be a powerful turning point for the community and for everyone attending!

PANELIST Estela Lugo

Estela was diagnosed with CMT when she was just 4 years-old. She resides on Long Island, NY, where she lives with her children, 11 year-old daughter Anabella and 9 year-old son Devin, both CMT-free. Estela also has a sister PANELIST Melissa, who has CMT. She is a 2001 graduate of Manhattan’s Fashion Institute of Chris Wodke Technology (FIT), and began designing furniture and wall décor after graduation. In 2008, she was named one of The Hereditary Neuropathy Foundation’s Team CMT Oprah’s “Women Who Make Beautiful Things” in “O” Founder and Manager Chris Wodke is changing the face of Home Magazine. Soon, her business, ONE Décor, was picked Charcot-Marie-Tooth one mile at a time. Chris is an up and listed on online Roommates Peel and Stick Décor. accomplished triathlete, marathon runner, and cyclist. Estela is an avid yogi and credits yoga as “the best thing And she has Charcot-Marie-Tooth. I've ever done for my CMT.” She considers herself an adaptive fitness activist and has experience using AlterG: an Diagnosed in 2010, Chris had a vision to share her athletic anti-gravity treadmill that can be used for physical therapy, feats with a community in need of increased awareness of injury prevention, and gait training and strengthening for the positive impact exercise has on your health, even for neurological patients. those affected by CMT.

A long-time member of the CMT community, HNF enlisted Starting an exercise program can be intimidating to many Estela to become a moderator for our CMT-Connect™ CMT patients, when tasks such as buttoning a shirt, workshops. She has generously committed her time to help navigating stairs, or opening a jar are daily challenges. Foot lead and teach other CMT patients in her community. deformities, balance deficiencies, and increased risk of falling can also discourage those living with CMT from HNF: Why did you choose your particular topic for the Summit? participating in regular forms of physical activity. Estela: However, there is an increasing body of clinical and I chose my topic for the Summit because I want to share my scientific information indicating that most CMT patients, success stories with the community and empower others when not contraindicated, should regularly participate in with CMT to take back as much control as possible over exercise and physical activity. their well being and lives. She founded Team CMT to provide a platform to raise aware- HNF: How has CMT affected your life? ness and funds for CMT research through athletic events. This Estela: grassroots community fundraising program is currently 196 In every way possible, but it has made me who I am today. members strong, across 37 states, and has an international 22 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

presence in Australia, England, Scotland, Canada, Vietnam, Turkey, Finland, Scotland, France, Poland, and Iran.

The Milwaukee native and Baby Boomer boasts an impres- sive and inspiring athletic resume that includes: • 2nd place in the Mobility Impaired Division at the Boston Marathon, where she also raised $10,000 for HNF in 2012. • 1st in the Physically Challenged Open Division of the Paratriathlon National Sprint Championship in Austin SPEAKER/MODERATOR Texas, 2012. • 2nd place in the same race in 2013. James Nussbaum, P.T., • PC Open Champion Duathlon National Championship 2014. • National Champion Paratriathlon Open Division Ph.D, S.C.S., E.M.T. Championship at the Paratriathlon National Triathlon Sprint Championship in 2014. Gaps in Available Patient Reported Outcomes • Represented Team USA at the Aquathon ITU World Championship in Chicago in 2015, and will represent the and Barriers to Therapy Development US at the World Championship in Cozumel in 2016. 2:05pm – 2:40pm • She’s also chronicled her life as an athlete with CMT in Dr. Nussbaum is the Clinical and Research Director of her book “Running For My Life, Winning For CMT.” ProHealth & Fitness PT OT, a physical and occupational HNF: How has CMT affected your life? therapy organization in New York City. He founded the organization in 2000 in an effort to provide skilled Chris: rehabilitation services to patients with all levels of abilities It has made me realize how blessed I am to still be active. I and disabilities. see that as a gift that I have chosen to use to raise awareness of CMT. I have many of the typical CMT issues, His career was fueled by his experiences as a physical but I am determined not to let it keep me from doing the therapy patient, working for Johnson & Johnson as a health things I love to help fight this condition. and fitness specialist, and as a volunteer Emergency Medical Technician. James returned to school after working HNF: What do you hope attendees take away from at Johnson & Johnson and graduated from Touro College the Summit? with a Masters of Science degree in Physical Therapy, and later earning his Ph.D. in Pathokinesiology. He is also a Chris: board-certified Sports Certification Specialist. I hope they will choose to be active if they are not, and be encouraged to keep being active if they are. I also hope Dr. Nussbaum sits on numerous clinical and academic they find others with CMT and make connections to build a advisory boards, and is an active member of the NYS Task sense of community. Force on Fall Prevention. He currently is a clinical instructor for numerous Physical Therapy schools, and teaches HNF: Anything else you’d like to share with us? biomechanics, human gait and kinesiology at Yeshiva University’s Stern College. Chris: We all have a role to play in the community. You do not His clinical and research focus has been on the effects of have to run marathons or write a book to make a innovative therapy interventions in medically complex difference. Use the talents you have to encourage others, patient populations. He has numerous ongoing IRB clinical raise awareness, and find a cure. trials, collaborating with many NYC physicians, hospitals, and agencies. Dr. Nussbaum has lectured and presented his To read more about Chris and her athletic accomplishments research at medical conferences throughout the US and and future goals, visit her website at www.run4cmt.com around the world.

He has a particular interest in finding ways to enhance and document patient improvements in activities of daily living, HNF-CURE.ORG 23

mobility, balance, function, and most importantly, quality Dr. Gudesblatt has authored articles appearing in profes- of life. In 2014, he became one of the first 3 certified sional literature on numerous topics, including movement AposTherapy providers in the US and is proudly active in disorders, tumors of the brain and spinal cord, neurologic educating physicians and patients alike. complications of pregnancy, stroke, familial inheritance of neurologic illness, and multiple sclerosis. He also partici- Dr. Nussbaum has been the recipient of numerous awards pates in clinical research at South Shore Neurologic, and designations and is passionate about improving the way involving MS and other neurologic diseases. He currently people live through clinical care, research, and education. serves on both the Science Advisory Board for the Heredi- tary Spastic Paraplegia Foundation and on the American Academy of Neurology Practice Standards Committee.

HNF: Why did you choose your particular topic for the Summit?

Dr. Gudesblatt: Digital Informatics will allow us to provide an objective pathway to identify subtle but critical disease impact and disease evolution and to help us better understand how PANELIST neurological disorders really impact those people with these illnesses. This could be an important bridge for the Mark Gudesblatt, M.D. unmet need of how to go apply research to clinical care. HNF: How has CMT affected your life? At HNF, our mission is to break down the barriers to Dr. Gudesblatt: accurate and timely diagnosis for CMT and IN patients. My life has been impacted by having serious and/or fatal Finding support among patients, caregivers, researchers, genetic disease within my own family. and HCPs is critical to meeting this challenge head on. HNF: What do you hope attendees take away from We are fortunate to have this vital support from Dr. Mark the Summit? Gudesblatt, medical director of the Comprehensive MS Care Center at South Shore Neurologic Associates, P.C. Dr. Gudesblatt: More objective and rich digital informatics of disease “I have long had an interest in accurate diagnosis for impact will help us define disease signature and disease people with neurological disorders beyond the simple progression. This approach will allow improved understand- commonly utilized all-inclusive labels such as ‘neuropathy’. I ing of treatment needs and targets. Better measurement of truly believe that an accurate diagnosis, more comprehen- change related to disease and therapy will provide im- sive objective analysis of disease impact, and change will proved opportunities to identify effective therapies. improve our ability to understand disease better and identi- fy appropriate and relevant effective therapies to those in need. My interest in Hereditary Neuropathies arises from such a desire to offer better opportunities to those with ‘uncommon disorders’. Rare disease is only as rare as considered or diagnosed.”

He graduated from Johns Hopkins University in 1976 and from Cornell University Medical College in 1980. His postgraduate training included a medical internship and neurologic residency at Mount Sinai Hospital, where he was the Chief Resident, as well as a Clinical Research Fellow in Neuromuscular Disease through the National Institute of Health.

Dr. Gudesblatt is certified by the American Board of Psychia- try and Neurology in the specialty of Neurology, is a diplo- mate in the American Academy of Pain Management, and has had additional training in Neuro-Rehabilitation. 24 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

PANELIST PANELIST Kenneth Attie, M.D. David Scher, M.D.

Dr. Attie has devoted 25 years to developing investigational Dr. Scher specializes in pediatric orthopaedic surgery, with drugs, primarily for growth disorders and neuromuscular special interests in children’s foot deformities including diseases. He joined Acceleron in November 2009 as VP of clubfoot, cerebral palsy, fractures in children and pediatric Medical Research. For Acceleron, he has been medical lead hip disorders. for Phase 1-3 studies with TGF-β superfamily investigational drugs for ESA-resistant anemias and neuromuscular Dr. Scher graduated from Brown University with an Sc.B. disorders. Acceleron has brought drug candidates into and honors in psychology in 1989 and from Duke University phase 2 studies for indications including Duchenne and FSH School of Medicine in 1993. He then completed his muscular dystrophies. He has held similar leadership orthopaedic residency training at the Hospital for Joint positions at Altus Pharmaceuticals and Insmed Inc., where Diseases in 1999. He received advanced fellowship training he helped gain FDA approval of an IGF-1/IGFBP-3 product. in pediatric orthopaedic surgery at the Children’s Hospital of San Diego, renowned for its longstanding tradition of innovation and leadership in pediatric orthopaedics. Prior to that, Dr. Attie worked for 12 years at Genentech, Inc., where he did research related to the TGF-β superfamily Dr. Scher’s primary focus is the clinical care of children with and was responsible for several phase 1-4 studies of musculoskeletal conditions, ranging from simple fractures recombinant human growth hormone and for obtaining to severe congenital and developmental disorders. He also marketing authorization for rhGH in chronic renal devotes substantial time and effort toward academic insufficiency, Turner syndrome, adult GH deficiency, and endeavors within the realm of pediatric orthopaedics, idiopathic short stature, as well as for a long-acting GH including service as the co-medical director of The Leon product. Dr. Attie was Assistant Clinical Professor of Root Motion Analysis Laboratory, where advanced Pediatrics at the University of California, San Francisco technologies are used for both research and clinical Medical Center, is board-certified in Pediatrics and Pediatric decision making to improve how children walk, and as the Endocrinology, and has over 50 publications in peer- principal investigator on numerous pediatric orthopaedic reviewed journals. Dr. Attie received a B.A. in Music from research projects. the University of Michigan, Ann Arbor and an M.D. from New York University Medical Center. Dr. Scher’s other academic and leadership roles include service as the education director of the pediatric orthopaedic service at HSS, lectures at regional and national courses on pediatric orthopaedics, and various committee positions and leadership leadership roles within the American Academy of Orthopaedic Surgery, the Pediatric Orthopaedic Society of North America, the Pediatric Orthopaedic Club of New York, and the American Academy of Cerebral Palsy and Developmental Medicine. HNF-CURE.ORG 25

Dr. Pfeffer has shared his expertise through many media outlets, including ABC News, the Associated Press, CBS News, CNN, Dateline NBC, the Los Angeles Times, Good Morning America, the New York Times, People magazine, Readers' Digest, Runner's World magazine, USA Today and the Wall Street Journal, and ABC’s Dancing with the Stars.

PANELIST Glenn Pfeffer, M.D.

Glenn B. Pfeffer, M.D., is Director of the Foot and Ankle Center at Cedars-Sinai Medical Center in Los Angeles, and Co-Director of the Cedars-Sinai/USC Dramatic Arts Dance Medicine Center. Dr. Pfeffer's primary clinical SPEAKER/MODERATOR interests involve reconstruction of the foot and ankle. His current research focuses on the three-dimensional imaging of complex deformity in patients with Charcot- Florian P. Thomas, M.D., Marie-Tooth Disease.

He is a past president of the American Orthopaedic Foot M.A., Ph.D., M.S. and Ankle Society, the American Association of Foot and Ankle surgeons, and the California Orthopaedic The Squeaky Wheel Gets the Grease: The Art of Association. He served on the national board of the Being a Successful Patient is to Know How to Get American Academy of Orthopedic Surgeons. Dr. Pfeffer is a board-certified orthopedic surgeon, a diplomate of the on Your Doctor’s Nerves and Feel Good About It American Board of Orthopaedic Surgery and a fellow of the American College of Surgeons. 3:00pm – 3:40pm We must all become our own best health advocates. He has written articles for numerous peer-reviewed scientific publications and edited seven books on the foot and ankle, For those living with Charcot-Marie-Tooth disease and for including Advanced Reconstruction of the Foot and Ankle; their caregivers, being the leading advocate for your health Orthopaedic Knowledge Update: Foot and Ankle; Current and wellness is essential to getting the right care and Practice in Foot and Ankle Surgery; Chronic Ankle Pain in the treatment you deserve. Athlete; Essentials of Musculoskeletal Care; and the Anno- tated Bibliography of the Foot and Ankle. Dr. Pfeffer is on CMT has been a big part of Dr. Thomas’ professional career the editorial board of the American Journal of Orthopaedics, for over 25 years. After obtaining his medical degree and serves on the U.S. Food and Drug Administration (FDA) an M.A. in psychology in 1982/1983, Dr. Thomas completed advisory panel for Devices and Radiological health, and his training in Neurology at Case Western Reserve reviews for multiple orthopaedic Journals. He lectures University in 1987, and in Neuroimmunology-Peripheral internationally, most recently with a focus on total ankle Nerve Disorders at Columbia University in 1990. replacement and Charcot-Marie-Tooth reconstructive surgery. He earned his Ph.D. in Molecular Biology at McGill Dr. Pfeffer received his bachelor's degree from Yale University, and joined St. Louis University in 1995. Since University. He earned his medical degree from the 1999, he has engaged in clinical trials and recently obtained University of Pennsylvania, where he completed a surgical a M.S. in Health Outcomes Research. internship and orthopedic residency. Dr. Pfeffer completed fellowships in both foot and ankle surgery at the University In September 2016, Dr. Thomas joined Hackensack of Texas, Houston and hand and microvascular surgery at University Medical Center as Chairman of the Neuroscience the University of California, San Diego. After completion of Institute and Director of the Multiple Sclerosis and his training, he served for six months with Project Hope as a Hereditary Neuropathy Centers. volunteer orthopedic surgeon overseas. 26 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

His research and experience with CMT includes: • Columbia University: Described specific microscopic sural nerve abnormalities in CMT1B. • CMTA: Chaired grant review committee for 4 years. • St. Louis CMTA Support Group: Co-led for 15 years. • Novel gene mutation: In 2006, he reported a novel gene mutation as the cause of one subtype of CMT (DI-CMT C). PANELIST • Pharnext Clinical Trial: In 2016 he enrolled the first patient in the Pharnext clinical trial for CMT1A. Debi Houliares HNF: Why did you choose your particular topic for the Summit? When Debi’s son Zach was first diagnosed with CMT Type 6 in 2014, after 14 years of doctors trying to figure it out, she Dr. Thomas: couldn’t believe there was a disease out there that no one People who live with a chronic illness are more likely to has ever heard of. live well, if they know a lot about it and can advocate for themselves. How could this be?

HNF: How has CMT affected your life? After researching on the internet, which didn’t provide a lot of information, her first call was to the Hereditary Dr. Thomas: Neuropathy Foundation, and spoke with HNF’s CEO and For 20 years, I have accompanied the family whose disease Founder Allison Moore. She was the very first person that mutation I identified. I visit the 94 year-old family patriarch was able to answer so many questions about CMT that all every year during our family vacation on Lake Michigan. I the doctors could not. have seen his grandchildren grow up, develop symptoms of CMT, and wonder if their children have CMT. This close CMT6 is a less common form of Charcot-Marie-Tooth relationship has given me a much better understanding of disease. In CMT6, symptoms can start in early childhood, what it means to live with CMT. teenage years, or adulthood. CMT6 involves development of optic atrophy with loss of vision or blindness, muscle HNF: What do you hope attendees take away from atrophy and weakness, loss of sensation, and balance and the Summit? gait difficulties. Dr. Thomas: Since Zach’s diagnosis in January 2014, The Houliares Family Attendees will acquire an in-depth understanding of how continues to bring awareness to this terrible disease in his patients can empower themselves to be active partners in community and beyond. Debi joined the HNF board of their own care, how to consider the pros and cons of directors to help raise funds for CMT6 and spread aware- engagement in clinical trials, and how to maximize ness. They have led 3 major fundraisers since his diagnosis. resilience and live well with a disease. HNF: Why did you choose your particular topic for Dr. Thomas lives with his wife and their blended family with the Summit? 5 children between the ages of 12 and 23. Dr. Thomas’ wife founded a magazine dedicated to artists in St. Louis. His Debi: daughter is an undergraduate at Fordham Lincoln Center, I know what this family went through trying to find not too far from the Summit location. answers to the “whys” that so many doctors could not do. CMT has been around for 100 years and yet so many doctors were unable to diagnosis Zach's condition. Never give up.

HNF: How has CMT affected your life?

Debi: Since Zach’s diagnosis in 2014 life has forever changed. Just knowing that Zach may not be able to walk one day, lose HNF-CURE.ORG 27

the use of his hands, and may be completely blind is not acceptable. I have made it my life's mission to continue to raise awareness and money for research.

HNF: What do you hope attendees take away from the Summit?

Debi: I hope that everyone attending the conference realizes that research is happening. People are working hard to find SPEAKER treatments and a cure for this disease. I want everyone to realize how important it is to bring this information back to their own communities and help in this fight to raise Timothy R. Coté, M.D., awareness.

HNF: Anything else you’d like to share with the community? M.P.H., C.E.O. Debi: Participating in a Clinical Trial: The Good, the Never give up! HNF has many resources, so use them. We are creating a place where people can go to help Bad and the Benefits find support. 3:45pm – 4:25pm Connect with Debi and learn more about her mission to Dr. Timothy R. Coté is a leading national regulatory expert raise awareness and find a cure for CMT6 here: in orphan drug development. With 23 years of Federal www.hnf-cure.org/zachsteam service at the FDA, NIH, and CDC, Dr. Coté recently served as the Director of the FDA Office of Orphan Products Development (OOPD) from Sept 2007 through May 2011.

In this role, he implemented the Orphan Drug Act and personally signed decisions on 1400+ orphan drug designation applications. An anatomic pathologist and medical epidemiologist, he has published 80 peer-reviewed articles on areas as diverse as HIV/AIDS-related malignancies, typhoid fever epidemics, and the impact of bicycle helmet laws on injury statistics. PANELIST Dr. Coté is founder and CEO at Coté Orphan; he directs and trains staff to create compelling regulatory submissions that Brian Loew are finely tuned to each client's business strategy and to the unwritten rules within the FDA. Brian Loew is a healthcare social network pioneer who created Inspire with the goal of accelerating medical Dr. Coté received a bachelor's degree from Syracuse research through safe, trusted online social networks. University, a Medical Doctorate from the Howard University Inspire is a global online support community of over 10 College of Medicine, and a Master's degree in Public Health million online users per year and 850,000 registered from Harvard School of Public Health. patients and caregivers, with a majority of members belonging to communities focused on rare diseases, cancer, or chronic conditions.

Brian has been an Internet entrepreneur for over 20 years. He founded worldweb.net, a content management software company that created and launched over 100 websites for major publishers including Hachette Filipacchi, Time Warner, and The Washington Post Company. Brian, his wife, and their two children live in Princeton, NJ. 28 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

PANELIST PANELIST Mario Saporta, M.D., Matthew Downing

Ph.D., M.B.A. Matt, his sister, and his father were all diagnosed with CMT at a fairly young age. Matt is now married and the father of four children, three of which have been diagnosed with Mario Saporta is an assistant professor of Neurology and CMT1A. Upon learning of their diagnosis, Matt became Human Genetics at UM and an adjunct professor of Neurol- active with the MDA and various CMT groups, including the ogy and Clinical Neurophysiology at Universidade Federal Hereditary Neuropathy Foundation. Then, in 2010, Matt Fluminense in Brazil. joined the HNF Board of Directors. Dr. Saporta is the new director of the MDA/CMT clinic at Currently, Matt is the Chief Marketing Officer at TriPlay, a the University of Miami, where he is developing a multidis- cloud services start-up in New York City. Prior to joining ciplinary clinic to provide specialized care for patients with TriPlay, Matt was Vice President of Marketing and Sales at neuromuscular genetic disorders, with a focus on the SiriusXM. Prior to SiriusXM, Matt spent a number of years inherited peripheral neuropathies. in Advertising and a Silicon Valley start-up that was After completing his Neurology training in his home acquired by DIRECTV. country of Brazil, Dr. Saporta underwent extensive training Matt is a graduate of The University of Michigan and he in neuromuscular disorders, with emphasis in the peripheral enjoys golf, biking, and spending time with his family. neuropathies, in centers in the United Kingdom (Institute of Neurology, University College London), France (Centre HNF: Why did you choose your particular topic for Hospitalier Universitaire de Bicêtre), and the US. the Summit?

He completed his Neuromuscular/Neurophysiology Matt: fellowship at the Detroit Medical Center, home to the I chose to participate in the panel on clinical trials because I largest inherited neuropathy clinic in the world, and was have primary experience as a patient participating in a CMT the first clinical research fellow of the NIH Inherited clinical trial. In 2009, I joined the High-Dose Vitamin C Neuropathy Consortium. (Ascorbic Acid) Trial through the CMT Center at Johns Hopkins Hospital in Baltimore, MD. While I was disappoint- Dr. Saporta has published extensively on the pathophysiol- ed that the study did not identify a viable therapy, I learned ogy of different types of inherited peripheral neuropathies, a lot during the study and I’m happy to share my observa- using various disease models, including patients’ skin tions as a patient to help improve future CMT trials. biopsies, knockin mouse models, and induced pluripotent stem cell derived motor neurons from patients with CMT. HNF: How has CMT affected your life? Dr. Saporta’s current research interest is the identification of downstream mediators of axonal degeneration in Matt: inherited neuropathies using cellular reprogramming and I’ve gone through six different surgeries to correct differentiation to create patient-derived neuronal cell lines deformities and damage caused by CMT. I also saw my for pathophysiologic studies. father spend the last decade of his life in a wheelchair because of CMT, suffering severe muscle contractures that caused him to lose control of his hands and lower legs.

Obviously I’m concerned about what the future holds for me and my family. My oldest son has already undergone HNF-CURE.ORG 29

three CMT-related foot surgeries and two of my other children are suffering from progressive CMT foot deformities that will likely require surgical intervention.

I hate CMT, and I’m committed to working with HNF and our partner organizations to find treatments and cures for CMT, so my children can grow up without the fear that they too might end up losing the ability to walk or use their hands. SPEAKER HNF: What do you hope attendees take away from the Summit? Michael Sereda, M.D. Matt: I want attendees to know that they are not alone in their fight with CMT. I want them to walk away with the belief Translational Medicine in CMT: Update, Pre- that their participation helped influence patients, doctors, clinical, and Clinical Trials researchers, and industry representatives to work together to treat and cure this terrible disease. 4:30pm – 5:00pm An HNF Scientific Advisory Board member since 2015, Dr. Sereda is a Professor of Neurology at the University Medicine Göttingen in Germany (UMG) and Independant Group Head at the Max Planck Institute of Experimental Medicine (MPIEM).

His domain of research includes Schwann cell biology, dis- ease mechanisms, experimental therapy and clinical (Phase II and III) trials, outcome measures, and biomarkers of CMT.

PANELIST Dr. Sereda serves as the Coordinator of the German CMT- NET network on Charcot-Marie-Tooth disease, and has ties to the German patient organisations (DGN), with CMT- René Goedkoop, M.D. France, CMT-Rete in Italy.

Over 25 years of experience in worldwide clinical product HNF: What is the focus of your CMT research? development with emphasis on “first in class” therapeutic solutions for inflammatory, neurologic and cardiovascular Dr. Sereda: disease, cancer, including experience in the field of medical We pursue a basic research interest in glial cell biology, devices and cell-based technologies. Clinical target axon-glia interaction, and mechanisms of diseases of indications included rare and ultra-rare genetic diseases the peripheral nervous system. We have generated a transgenic rat model of the most frequent human neuropathy, Charcot-Marie-Tooth disease type 1A (CMT1A). He worked in start-up and large companies, including This disease is associated with a partial duplication of Apoxis, Modex, Serono, Eli Lilly and Centocor at a global chromosome 17 which leads to an overexpression of the level. He has directly interacted with key regulatory tetraspan protein PMP22. agencies. In conjuncture, he has worked as an independent expert clinical development strategy consultant for a Transgenic “CMT rats“ expressing additional copies of this variety of biotech companies, and has conducted due gene share characteristic clinical features of the human dis- diligences and helped create the business plan for de ease, including muscle weakness, reduced nerve conduction novo biotech companies for VCs. He also was on the velocities, and marked Schwann cell hypertrophy result- board of directors at Neovacs. He received his MD at the ing in onion bulb formation. The CMT rat allows a better University of Amsterdam followed by a residency in understanding of the cellular disease mechanism operating cardiopulmonary surgery. in human CMT1A, and is helpful in the analysis of modifier genes, epigenetic factors, and in the evaluation of experi- mental treatment strategies. 30 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

In an attempt to translate findings from the animal model Even though the incidence of CMT is greater than that of to humans, we have recently identified biomarkers of dis- MS, CMT goes largely unrecognized. Patients go years ease severity in CMT1A patients. We are currently validating without a proper diagnosis, Health Care Provider (HCP) markers in patients across Europe which should help us to don’t have the knowledge to help, and researchers are perform clinical trials in the near future. Moreover, we are faced with limited information to develop drug therapies involved in clinical (Phase II and III) trials in CMT1A. and clinical trials for CMT patients.

HNF: What do you hope attendees take away from It’s more important than ever to keep pushing the bound- the Summit? aries of raising awareness within the CMT patient and HCP communities. Without awareness, we don’t have a voice. Dr. Sereda: I hope to increase awareness and participation in CMT-NET: And this Summit speaker has something to say. a network and news hub on CMT research for doctors, scientists, and patients. Robert Moore, husband to Allison Moore, CEO and Founder of HNF, will be discussing the challenges of disease For more information on Dr. Sereda and his research, state awareness at the Patient-Centered Charcot-Marie- please visit: Tooth Summit. Max Planck Institute of Experimental Medicine: http://bit.ly/2buoE6R HNF: Why did you choose your particular topic for CMT-NET: www.cmt-net.de/ the Summit? Robert: The biggest challenge for those living with CMT is bringing awareness of their CMT symptoms to their HCPs. I’ve seen Allison go through countless visits with medical profession- als that only dismissed her symptoms. By raising awareness of the disease to the medical community, patients will have a fighting chance to get diagnosed quickly and correctly.

HNF: How has CMT affected your life?

SPEAKER Robert: Watching Allison have trouble walking, or performing Robert Moore simple tasks such as buttoning a shirt or opening a bottle, has given me a very different perspective for anyone living with a chronic debilitating disease. She walks with leg The High-Arched Foot: This is the Begin- braces, but will still suffer frequent falls, often resulting in ning? The Disease Awareness Challenge broken bones, and sometimes a broken spirit.

But that has not slowed Allison down at all! She is a 5:05pm – 5:25pm remarkable force of determination, persistence, Did you know? and strength.

Multiple Sclerosis is the most common autoimmune HNF: What do you hope attendees take away from disorder affecting the central nervous system, with more the Summit? than 2.3 million people affected worldwide. Robert: Charcot-Marie-Tooth disease is the most commonly I hope attendees take away a renewed sense of commit- inherited peripheral nerve disorder, and affects about 2.8 ment to raising CMT awareness. Whether it’s as a patient, million people worldwide. caregiver, or HCP, let’s make a promise to be 100% commit- ted to meeting the CMT awareness challenge head on! If you walked up to a group of people in your town, your city, your school, or your neighborhood…and asked them if they ever heard about MS, the majority would say “Yes.”

Now ask them if they ever heard about CMT...the majority would say “What?” HNF-CURE.ORG 31

SPOTLIGHT ON A RESEARCHER: ROBERT PRIOR IS INVESTIGATING CMT AND HE IS A CMT PATIENT

My name is Robert Prior and I’m from Ireland. I am currently a 1st year PhD student in the lab of Neurobiology at KU Leuven and VIB, in Leuven, Belgium. My project is investigating axonal transport defects as a pathological mechanism in Charcot-Marie-Tooth disease (CMT) type 1A and modification through histone deacetylase 6 inhibition. I obtained my B.Sc. in Biomedical Science at Maynooth University and my M.Sc. in Regenerative Medicine at the National University of Ireland, Galway, in which I received an overall first class honour grade. I am also a CMT type 1X patient and I have several affected family members. Each family member is affected differently, ranging from moderate walking impairments to being completely wheelchair dependant.

Unfortunately, there was, and still is, virtually no CMT research being conducted in Ireland, so I decided to move to Belgium. There are several research institutions in Belgium that have made landmark discoveries that have helped advance our knowledge of CMT over the past three decades. In addition, my current lab identified a possible treatment for the axonal form of CMT, CMT type 2, which I felt could be applicable to the demyelinating form of CMT, CMT type 1, and my promotor, Professor Ludo Van Den Bosch, shared the same vision. So, that is now our current ongoing project.

As a patient, I felt I couldn’t influence the CMT research field as I was constantly on the ‘side-lines’ of the research. But as a researcher, I am more involved and I now can contribute to moving the CMT research field forward and hopefully, help to advance our knowledge about this disease. As a patient, there is solace in knowledge about what, why, and how the disease is affecting you, as well as what are the possible treatments available and which are on the horizon. As a researcher, I feel I am in the perfect seat to understand and answer these questions now. 32 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

Abstracts INHIBITION OF HISTONE DEACETYLASE 6 AS A THERAPEUTIC STRATEGY FOR CHARCOT-MARIE-TOOTH DISEASE

Prior R1,2, Benoy V1,2, d’Ydewalle C1,2, Vanden Berghe P3, and improved significantly when the mice or neurons were Van Den Bosch L1,2 treated with HDAC6 inhibitors.

1 Laboratory of Neurobiology, Vesalius Research Center We currently focus on CMT type 1A, the main cause of CMT, (VIB), Leuven, Belgium. 2 Leuven Research Institute for which is caused by a duplication of a segment of chromo- Neuroscience and Disease (LIND), KU Leuven, Belgium. 3 some 17p11.2 containing the gene encoding peripheral Laboratory for Enteric Neuroscience, Translational Research myelin protein 22 (PMP22). PMP22 is mainly expressed by Center for Gastrointestinal Disorders, KU Leuven, Belgium. Schwann cells, the cells that myelinate neurons in the peripheral nervous system. We are currently differentiating Charcot-Marie-Tooth disease (CMT), the most common patient-derived induced pluripotent stem cells (iPSCs) to inherited neurodegenerative disorder of the peripheral Schwann cells and motor neurons to investigate external nervous system, is subdivided into two main subtypes. CMT influences of Schwann cells on axonal transport in motor type 1 is the demyelinating form, while CMT type 2 is the neurons. Furthermore, we will investigate whether HDAC6 axonal form, although several intermediate forms exist. inhibition has an effect in this experimental system. CMT is classically a length-dependent disease, in that it Additionally, we are investigating whether treatment with effects the longest neurons in the body and thus the a selective HDAC6 inhibitor is beneficial in two CMT type 1A muscles in the peripheral regions are affected first and transgenic mouse models. We are focussing on motor and foremost. The majority of CMT patients share a classical sensory performances, nerve conduction studies, axonal phenotype with shared pathological hallmarks, such as transport, and other CMT pathological hallmarks. walking impairments, muscular atrophy, reduction in nerve conduction, etc. In addition, patients also share molecular In conclusion, we showed that selective HDAC6 inhibition pathological hallmarks like the breakdown in the transport has a positive effect on axonal transport along microtu- of organelles and vesicles in neurons in a process called bules, which act as molecular tracks for motor proteins and axonal transport. Currently, there is no cure or effective facilitates axonal transport of cargos. Moreover, HDAC6 treatment available to CMT patients. inhibition has a beneficial effect in a number of CMT subtypes. As a consequence, this research could lead to the We developed and characterized transgenic mice express- development of a new therapeutic strategy for a currently, ing two different mutations in the 27-kDa small heat-shock untreatable debilitating disease. protein gene (HSPB1) (S135F and P182L) in neurons only. Mutations in HSPB1 cause axonal CMT or distal hereditary motor neuropathy. Furthermore, the mice showed all features of CMT. We then demonstrated that there were axonal transport deficits in these transgenic mice. These axonal transport deficits could be rescued after treatment with a histone deacetylase 6 (HDAC6) inhibitor. In addition, the motor and sensory deficits present in these mutant HSPB1 mice could be rescued by treating these mice with HDAC6 inhibitors.

In a follow-up study, similar deficits in the axonal transport in sensory neurons were observed in another transgenic CMT type 2 mouse model. These mice have an endogenous mutation in the gene that codes for glycyl-tRNA synthetase (Gars). We also could demonstrate that both the axonal transport deficits, as well as the nerve conduction, was HNF-CURE.ORG 33

RESULTS FROM A PHASE 1 HEALTHY VOLUNTEER STUDY OF ACE-083, A NOVEL, LOCALLY-ACTING MUSCLE AGENT

Glasser CE1, Gartner MR2, Boes BL3, Pearsall RS1, Zhang X1, CONCLUSIONS Sun J1, Vidal B1, Leneus A1, Hankin M1, Sherman ML1, Attie KM1 Local administration of ACE-083 was generally well-tolerat- ed and associated with dose-dependent increases in muscle 1Acceleron Pharma, Cambridge MA, USA; 2Celerion, volume. These results support further studies of ACE-083 in Lincoln NE, USA; 3Bryan Health, Lincoln NE, USA neuromuscular diseases with focal loss of muscle strength and function, including Charcot-Marie-Tooth disease. BACKGROUND

ACE-083 is an investigational protein therapeutic that acts as a localized ligand trap for myostatin and other negative regulators of muscle growth. In wild-type mice, mdx model of Duchenne muscular dystrophy, and SOD1 model of amyotrophic lateral sclerosis, local injection of ACE-083 into a target muscle produced dose-dependent increases in muscle mass and force without systemic pharmacodynamic (PD) effects.

METHODS

A single-center, double-blind, placebo-controlled, dose escalation study evaluating safety, tolerability, pharmacoki- netics, and PD effects of ACE-083 in healthy, postmeno- pausal women. Subjects were randomized to receive ACE-083 or placebo, administered as 2-4 EMG-guided injections into the right rectus femoris (RF) or tibialis anterior (TA). Cohorts 1-3 (50, 100, 200 mg; RF) were dosed on Day 1, Cohorts 4-5 (100, 200 mg; RF) on Days 1 and 22, and Cohorts 6-7 (100, 150 mg; TA) on Days 1 and 22. Muscle volume was assessed by MRI; strength by fixed and hand- held dynamometers.

RESULTS

Mean % change from baseline in right RF muscle volume 3 weeks post last dose was +0.1%, +4.5%, +4.5%, +7.3%, and +14.5% in ACE-083-treated subjects from Cohorts 1-5 compared to +0.1% in placebo subjects, respectively. Mean % change from baseline in right TA muscle volume 3 weeks post last dose was +5.0% and +8.9% in Cohorts 6 and 7 compared to -0.1% in placebo subjects, respectively. Changes in the uninjected left RF and TA muscle were not significant. In all cohorts, injected muscle volume remained increased 8 weeks post last dose. Correlations between strength and muscle volume were not statistically signifi- cant in these healthy volunteers. All AEs were grade 1-2 and reversible. Frequent related AEs (≥15%) included injection site pain, muscle twitching, myalgia, and injection site reaction, with similar incidences to placebo. 34 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

FUNCTIONAL OUTCOME MEASURES IN PATIENTS WITH CHARCOT MARIE TOOTH, A RETROSPECTIVE REPORT ON PHYSICAL FUNCTION AND QUALITY OF LIFE.

James Nussbaum, PT, PhD, SCS, EMT ProHealth & Fitness PT METHODS OT New York, NY 10023, USA retrospective analysis of 12 consecutive patients diagnosed BACKGROUND with CMT over a 24 month period was studied (8 males, median age = 51.67 years, median time since diagnosis Patients with Charcot Marie Tooth (CMT) often present with =18.42 years, 10 patients had ankle foot orthoses, 3 pa- numerous signs and symptoms limiting mobility, balance, tients used a walker and one used a cane for mobility. Each strength, and activities of daily living (ADL). These factors patient was assessed using the 20’ walk for selfselected gait and others, for many people, significantly impact indepen- speed, Timed Up and Go (TUG) for dynamic balance, Sit To dence and quality of life (QOL). Improving QOL is the goal Stand in 30 seconds ((STS(30)) for lower extremity function- of most patients, those with CMT and otherwise, and al strength, Berg Balance Scale (BBS) for static and dynamic therefore should be very high on the priority list for health- balance, Dynamic Gait Index (DGI) for ambulation stability, care providers. In order to ensure patient centered goals are Grip Dynamometry for grip strength, Lower Extremity Func- being addressed, patient centered assessments are critical. tional Scale (LEFS) for lower extremity reported impair- Patient centered functional measures impacting QOL were ment, the Upper Extremity Functional Index (UEFI) for assessed in 12 consecutive patients diagnosed with CMT and upper extremity reported impairment, Spatiotemporal 2 are summarized below. Dimensional Laser Gait Analysis (SDLGA) for specific gait characteristics, including step length (SL), single limb support (SLS), and Velocity (V) for self-selected gait speed, and the Short Form (36) Health Survey (SF-36) for QOL.

RESULTS

The patients diagnosed with CMT demonstrated below normal values for all measures studied. Mean values are displaced in the chart below.

V (cm/sec) R SL (cm) L SL (cm) R SLS (%) L SLS (%) BBS max 56 TUG (sec) STS (30)

72.88 44.3 44.58 33.92 34.03 31.18 19.86 3.33

R grip (psi) L grip (psi) LEFS UEFI SF-36 DGI max 80 max 80 max 100 (max 24)

31.18 27.30 35.0 50.58 6.53 15.67

DISCUSSION CONCLUSIONS

Each person has a different hierarchy of factors which The utilization of patient centered objective measures across impact physical function and QOL. In this retrospective multiple domains, will enable a better understanding of study, we examined numerous valid and reliable measures physical function and QOL in patients with CMT at baseline, which quantify functional and reported characteristics of progression over time, and each patient’s response to impacting function and QOL. The patients we examined treatment. demonstrated significantly lower than normal scores in mobility, strength, balance, gait, and QOL. HNF-CURE.ORG 35

A PIVOTAL PHASE III STUDY (PLEO-CMT) ASSESSING THE EFFICACY AND SAFETY OF PXT3003 IN PATIENTS WITH CHARCOT-MARIE- TOOTH DISEASE TYPE 1A: A PROGRESS UPDATE

Goedkoop R, Daoust A, Vouidibio R, Murphy NP, Cohen D RESULTS

Pharnext, Issy-Les-Moulineaux, France As of the time of writing, the PLEO-CMT study is on sched- ule. A status update on the number of active investigational BACKGROUND sites, screened CMT1A patients and screen failures, random- ized patients and dropouts will be presented. To date, no treatment is available for Charcot-Marie-Tooth type 1A (CMT1A) disease. PXT3003 is a fixed combination CONCLUSIONS pleodrug comprising baclofen, naltrexone and sorbitol found to be safe and well tolerated in a multicenter, A pivotal phase III trial assessing the safety and efficacy of a randomized, placebo controlled phase II study in adult fixed combination pleodrug known as PXT3003 comprising outpatients with mild to moderate CMT1A (Attarian et al., baclofen, naltrexone and sorbitol in the treatment of 2014). Moreover, this study provided preliminary evidence of CMT1A has been launched and is progressing as planned. clinical efficacy of PXT3003 compared to placebo, which manifested as a modest improvement beyond stabilization of the disability. These findings could herald identification of a therapeutic approach capable of early, meaningful change in disease course, based on comparison to placebo and meta-analysed data from multiple clinical CMT1A studies and justify further investigation of PXT3003 (Mandel et al., 2015). Consequently, in consensus with regulatory agencies (FDA and EMA), a pivotal phase III was initiated in December 2015 to assess the efficacy and safety of PXT3003 in patients with CMT1A.

METHODS

The pivotal study is designed to assess the safety and efficacy of a low and high dose of PXT3003 (Pharnext) compared to placebo in a randomized, double-blind, placebo-controlled fashion (NCT02579759). Three-hundred eligible patients with confirmed genetic diagnosis of CMT1A are planned to be equally randomized into the 3 study arms before the end 2016. The Overall Neuropathy Limitations Scale (ONLS) will be used as the primary efficacy endpoint of the study. Safety and secondary disease-related outcomes will equally be assessed. The medication period will be 15 consecutive months with a 9-month extension study planned. 36 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

HOSPITAL ADMISSIONS AMONG INDIVIDUALS WITH CHARCOT-MARIE-TOOTH DISEASE IN FLORIDA, USA

Xinliang Liu, PhD, Department of Health Management individuals, 60.6%). The majority of individuals incurred a and Informatics, University of Central Florida, Orlando, charge between $10,000 and $100,000 (330 individuals, Florida, USA 82.9%). Most individuals were discharged home (213 individuals, 53.5%). Li Ge, MD, Department of Pathology, Orlando Health, Orlando, Florida, USA CONCLUSIONS

BACKGROUND Hospital discharge records can be used to identify individu- als with CMT and characterize inpatient services received by Charcot-Marie-Tooth disease (CMT), also known as peroneal them. Further research should explore other data sources muscular atrophy, is the most common inherited neuropa- and present a more comprehensive picture of all health thy. But with a prevalence of 1 in approximately 2,500 services (inpatient, outpatient, and prescription drugs) used people, little information exists regarding the inpatient by individuals with CMT and associated economic burden. care used by individuals with CMT. This study aimed to document the characteristics of individuals with CMT who were hospitalized.

METHODS

This study had a cross-sectional design. The 2012 Healthcare Cost and Utilization Project (HCUP) State Inpatient Data- base (SID) of Florida was used to identify individuals with CMT. If an individual had multiple hospital admissions, only the first hospitalization record was analyzed. Patient demographic characteristics, clinical diagnoses, length of stay (LOS) and hospital charges were reported.

RESULTS

Three hundred and ninety-eight individuals with CMT were identified and 549 hospital admissions were associated with these individuals. One hundred and seventy-four (43.7%) out of 398 individuals with CMT aged 65 years and above. Females accounted for 200 individuals (52.3%). Non-Hispan- ic white accounts for 348 individuals (88.1%), followed by Hispanics (20 individuals, 5.1%), Non-Hispanic African- Americans (19 individuals, 4.8%), and individuals from other racial/ethnical groups (8 individuals, 2.0%). A majority of individuals with CMT (247 individuals, 63.8%) lived in a zip code with median household income above the national average. The major payer was Medicare, followed by private insurance, Medicaid, self-pay, and other. The five most common primary diagnostic categories were related to the circulatory system, digestive system, injury and poisoning, musculoskeletal system/connective tissue, and respiratory system. The major treatments were procedures performed on the musculoskeletal system, cardiovascular system, digestive system, integumentary system, and other. Most individuals had a LOS of no more than 4 days (241 HNF-CURE.ORG 37

AN ONLINE SURVEY OF NEUROLOGISTS ABOUT CHARCOT-MARIE- TOOTH DISEASE TYPE 1A

Paoli X1, Chalandon C1, Cohen D1. RESULTS

1Pharnext, Issy-Les-Moulineaux, France Altogether respondents followed a pool of over 2,000 CMT1A patients and had mainly hospital-based activities (79%). As an BACKGROUND entry point in the CMT patient journey, neurologists declared adults usually seek for medical care due to symptoms alone Charcot-Marie-Tooth (CMT) disease refers to a heteroge- rather than their family history of CMT. For pediatric patients, neous group of inherited, progressive, chronic peripheral family history seems to be more decisive. For most patients, neuropathies. Presently incurable, CMT type 1A (CMT1A) is general practitioners, pediatricians and neurologists are the an autosomal dominant and demyelinating subtype of CMT. first physicians visited before reaching CMT experts. Patients Although it is the most frequent form, CMT1A prevalence usually do not suspect they suffer from CMT1A before diagno- remains low with around 160,000 patients both in Europe sis is confirmed. Physicians use clinical symptomatology, and the US. It is thus classified as an orphan disease. Our electrophysiology and genetic testing as primary diagnosis survey aimed at better understanding the CMT1A patient tools. Most patients seem to get diagnosed within two years journey across the US and European healthcare systems, after first symptoms and before the age of 30. The vast from first symptoms to management with supportive cares, majority of their patients suffer from mild to moderate CMT1A and also identifying potential barriers. (>80%). Physical therapy, orthotics and pharmacotherapy for METHODS neuropathic pain are the most frequent supportive cares.

In October 2014, an online questionnaire was administered CONCLUSIONS to 128 neurologists from the US and Europe. Respondents This survey offers a better understanding of the current were screened on their level of clinical activities (>75%), CMT1A patient journey. Bottlenecks have been identified ability to diagnose CMT and number of CMT patients where disease awareness programs developed by both managed (> 5). neurology societies and patient organizations could be helpful.

DEVELOPMENT OF IFB-088

Callizot N1, Le Bloas R1, Martin A1, Miniou P1, Guédat P1. stressed cells. Thus, IFB-088 is expected to have a high 1InFlectis BioScience, Nantes, France. safety profile regarding its mechanism of action (MOA). IFB-088 has suitable in vitro and in vivo ADME profile to Currently, there is no cure for Charcot-Marie-Tooth disease treat diseases involving the peripheral nerve system. Proofs (CMT) and no medical therapy capable of preventing the of concept of IFB-088 efficacy were obtained in animal progression of the disease. Current treatments are symp- models of CMT-1A and CMT-1B. We will present MOA, tomatic and supportive. ADME profile and the latest results obtained on the PMP22 transgenic rat model of CMT-1A. We have already demon- We have developed IFB-088 a disease modifying treatment strated that IFB-088 by reducing the amount of PMP22 of demyelinating forms of CMT. IFB-088, a small molecule, protein improves motor coordination, diminishes abnormal is targeting the translation arm of the Unfolded Protein gait, restores muscle strength and reduces neuropathic pain Response (UPR) to restore Endoplasmic Reticulum (ER) in CMT-1A rat model. proteostasis by inhibiting PPP1R15A (GADD34) involved in protein folding process control that improves cells’ ability to By acting on a molecular check-point, IFB-088 drug candi- deal with misfolded proteins. PPP1R15A being only ex- date has the potential to be potent in different CMT pressed in cells during stress-induced protein misfolding, subtypes. IFB-088 already got orphan drug designation IFB-088 is strikingly specific for stressed cells, avoiding status from EMA and FDA, and it is anticipated that it will persistent inhibition of protein synthesis in normal, non-ER- be in clinic by mid-2017. 38 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

THERAPEUTIC RESEARCH IN ACCELERATED DISCOVERY (TRIAD) AND HNF ASSETS FOR CHARCOT-MARIE-TOOTH (CMT)

Allison Moore, Sean Ekins and TRIAD members What we have found as a rare disease patient driven foundation, is that we have a vested interest in the out- Hereditary Neuropathy Foundation, 401 Park Avenue comes and an urgency to make things happen. We do not South, 10th Floor, New York, NY 10016 have unlimited resources as many large foundations do, so we have to be smart about investing in science and look for The Hereditary Neuropathy Foundation (HNF) was founded patient-centered research collaborations that will get in 2001 to get the research on Charcot-Marie-Tooth (CMT) treatments to patients as soon as possible. We rely on our moving. This lead to the development of the Therapeutic scientific advisory board and the scientists in our network. Research in Accelerated Discovery (TRIAD) as a collaborative TRIAD along with our Global Registry for Inherited Neu- model with academia, government and industry, enabling ropathies (GRIN), CMT Research Network (CMTRN), and our funding of key research priorities for many forms of the CMT Inspire community represent valuable assets to help disease. HNF have since funded research in the USA, UK and CMT research and development. Germany working on different forms of CMT. HNF also plays a critical role in advising biopharmaceutical compa- We are nimble and committed to improving lives for all nies looking for knowledge from key opinion leaders, patients and families living with CMT. conducting focus groups with patients and caregivers to help create viable clinical trial designs and assistance in setting up clinical sites to conduct the trials and patient engagement for CMT.

PROMOTING MYELIN REPAIR THROUGH DIET AND DRUG THERAPIES

Notterpek, Lucia, PhD

Departments of Neuroscience and Neurology, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, USA

Myelin-forming glial cells of the peripheral nervous system called Schwann cells have a remarkable capacity to repair damaged myelin. While this regenerative capacity is impacted by aging and disease, our studies indicate that Schwann cells robustly and positively respond to a variety of dietary modulations, including caloric restriction. We have identified small molecules that can in part mimic the beneficial effects of dietary restriction and we are now testing such molecules in neuropathic rodents. The goal of our study is to enhance the myelin repair capacity of Schwann cells in hereditary neuropathies, while preserving neuronal viability and improving skeletal muscle function. HNF-CURE.ORG 39

Chetlin RD, Layner KN, Triscuit AM, Ensey J, Sereda MW, Nave KA, Rader EP, Baker BA. Resistance-Type Exercise Results in Functional Adaptation and Reduced PMP22 Gene Expression in CMT Rat Muscle. Med Sci Sports Exerc. 2015. May;47(S1):443-449. RESISTANCE-TYPE EXERCISE RESULTS IN FUNCTIONAL ADAPTATION AND REDUCED PMP22 GENE EXPRESSION IN CMT RAT MUSCLE

R.D. Chetlin2,1, J. Ensey1, K.N. Layner2,1, A.M. Triscuit2,1, RESULTS M.W. Sereda3, K.-A. Nave3, E.P. Rader1 and B.A. Baker1 Endogenous PMP22 gene expression was 3.3-fold greater in 1National Institute for Occupational Safety and Health CMT skeletal muscle vs. WT. PMP22 transgene expression in (NIOSH), Health Effects Laboratory Division, Morgantown, the SSC training group was 4.9-fold lower vs. the ISO WV 26506, USA training group, and transgene expression was ~2-fold greater in unloaded vs. loaded limbs. Expression reductions 2 West Virginia University, School of Medicine Morgantown, in the PMP22 transgene and endogenous gene in CMT WV 26505, USA SSC-trained animals were highly correlated (r=0.92, p=0.001). Absolute ISO force (p<0.001) and muscle mass 3Department of Neurogenetics, Max-Planck-Institute of (p=0.002) was greater in WT vs. CMT. For CMT rats, SSCs Experimental Medicine, Göttingen, Germany resulted in relative increases in isometric force (40.2%), Charcot-Marie-Tooth (CMT) Disease is the most commonly normalized muscle mass (10.2%), and static muscle quality inherited sensorimotor peripheral neuropathy (1:2,500) and (66.4%, p=0.08) above ISO. has no known cure; CMT1A is the most prevalent type CONCLUSION (~50-70%) and caused by overexpression of a 22kDa peripheral myelin protein (PMP22). This results in reduced These findings suggest that resistance-type (SSC) training myelin integrity, myelin degradation, and skeletal muscle enhances muscle adaptation and reduces PMP22 gene weakness and atrophy. Human CMT exercise studies have expression in transgenic CMT rats. demonstrated improvements in function; however, no study has examined integrated physiologic and perfor- mance outcomes in transgenic CMT animals.

PURPOSE

To examine effects of chronic resistance-type training in a CMT1A rat model, using stretch-shortening contractions (SSCs), on muscle performance, physiology and PMP22 gene expression.

METHODS

Dorsiflexor muscles of young (12 wks) wild-type (WT) and

CMT1A rats (rats expressing TgPMP22mouse ~1.6-fold over wild-type levels) were exposed 3 times/week for 4.5-weeks to a protocol of either isometric (ISO) contractions (serving as a metabolic control) or 80 maximal, non-injurious SSCs per exposure in vivo. Twenty-four hours after final expo- sure, rats were weighed, exsanguinated, and left (loaded) and right (contralateral control) hind-limb soft tissues were harvested and allocated for future procedures. Initial (control) and final (ISO or SSC) static muscle performance and static muscle quality were quantified for the tibialis anterior. RT-PCR was used to determine PMP22 expression in both endogenous (rat) and trans (mouse) genes. 40 PATIENT-CENTERED CHARCOT-MARIE-TOOTH SUMMIT

Baker BA, Chetlin RD, Layner KN, Triscuit AM, Ensey J, Sereda MW, Nave KA, Rader EP. Chronic Resistance-Type Exercise Results in Enhanced Dynamic Muscle Adaptation in CMT Rats. Med Sci Sports Exerc. 2015. May;47(S1):92-104. CHRONIC STRETCH-SHORTENING CONTRACTION RESISTANCE-TYPE EXERCISE RESULTS IN ENHANCED DYNAMIC MUSCLE ADAPTATION IN CMT RATS

B.A. Baker1, R.D. Chetlin2,1, K.N. Layner2,1, A.M. Triscuit2,1, RESULTS J. Ensey1, M.W. Sereda3, K.-A. Nave3 and E.P. Rader1 When normalized to initial values, the percent change in 1National Institute for Occupational Safety and Health positive work was increased ~48% in CMT1A rats following (NIOSH), Health Effects Laboratory Division, Morgantown, SSC exposure compared with ISO exposure (p < 0.05). There WV, 26506, USA. was a trend for increased cyclic force in WT rats following SSC exposure compared with CON (p = 0.07). Dynamic 2 West Virginia University, School of Medicine muscle quality was enhanced ~100% in the CMT1A ISO Morgantown, WV (p = 0.01) and ~150% in the CMT1A SSC (p< 0.001) rats following training. 3Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany CONCLUSION

Charcot-Marie-Tooth (CMT) Disease is the most common These data demonstrate that SSCs may be the preferred inherited neuropathy (1:2,500), and CMT1A is the most mode of resistance-type training, given that it enhanced prevalent variant of the disease (~75%). CMT1A is caused by both dynamic muscle performance and dynamic muscle a duplication of the peripheral myelin protein of 22kDa quality. Our findings suggest that when an established (PMP22), which affects myelin integrity and results in myelin fundamental model of CMT1A is mechanically loaded using degradation; leading to progressive skeletal muscle weak- a validated, in vivo, high-intensity resistance-type training ness and atrophy. CMT has no known cure, is non-terminal; regimen the results promote a dynamic adaptive response, and, thus, may affect workers in all occupational settings. which is critical for establishing an achievable translational paradigm for increased quality of life and independence in PURPOSE human patients. The purpose of this study was to determine if a CMT1A Key Words: CMT1A, Resistance Exercise, Stretch-shortening Contractions, rat model exposed to chronic resistance-type training Adaptation, Muscle physiology utilizing stretch-shortening contractions (SSCs) results in an adaptive response. Disclaimer: “The findings and conclusions in this report (abstract/presenta- tion) have not been formally disseminated by the National Institute for METHODS Occupational Safety and Health and should not be construed to represent any agency determination or policy.” Dorsiflexor muscles of young (12 wks) wild-type (WT) and CMT1A rats were exposed 3 times per week for 4.5-weeks to a protocol of either isometric (ISO) contractions (serving as a metabolic control) or 80 maximal, non-injurious SSCs per exposure in vivo. Twenty-four hours after the final exposure, rats were weighed, exsanguinated, and the left (loaded) and right (contralateral control) hind-limb soft tissues were harvested. Initial (CON) and final (for ISO or SSC) dynamic muscle performance and dynamic muscle quality (SSC peak force/normalized muscle weight) were quantified for the dorsi-flexor muscles and the tibialis anterior, respectively. HNF-CURE.ORG 41

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