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Drugs Tested in PRF- Funded Clinical Trials Increase Estimated Lifespan of Children with Progeria

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Drugs Tested in PRF- Funded Clinical Trials Increase Estimated Lifespan of Children with Progeria WWW.PROGERIARESEARCH.ORG • SUMMER 2014 The PRF Team FANTASTIC NEWS! Drugs tested in PRF- Message from the President 2 funded clinical trials increase estimated newslifespan of children with Progeria In Loving Memory 3 In a stunning development, a first-ever study to assess whether treatments Longevity Study 4 influence patient survival shows that the medications tested in the PRF- funded Boston-based Progeria clinical trials increased lifespan for children Clinical Trial Updates 5 with Progeria. PRF’s Latest The study results reveal that children with Progeria receiving lonafarnib, Research Grants 6-7 along with two other drugs added in a later “triple therapy” study, had an Annual Report 2013 8-9 80 percent lower risk of death compared to the untreated group. Lonafarnib is the drug tested in the first-ever Progeria trial in 2007, and HBO’s Life According to Sam 10 proved to be an effective treatment in several A Tribute to Sam, areas, including the PRF’s Founding Inspiration 11 critical cardiovascular system. PRF On The Move! 12-13 This is the first Night of Wonder 2014 13 evidence of any treatments influencing Special Events & Miracle Makers 14-15 survival for this fatal disease – an historic Join our BACK finding in our quest to Goodsearch Team! COVER improve health and extend the lives of children with Progeria. We’re a Cam, Zach and Miles love their trophies, awarded by PRF during 4-Star See page 4 their March visit to Boston Children’s Hospital for completing the triple therapy trial. Charity! for details. See page 5 for the latest on clinical trial activities. See page 12 for details PRF’s Mission: Message from the President To discover treatments and Executive Director and the cure for Progeria Hello everyone, and its aging-related At a TedX event in Charlottesville* in November, 2013, Dr. Leslie Gordon, PRF’s Medical Director, shared her disorders. “Secret Sauce” for making anything possible. Dr. Gordon Staff: Public Awareness Committee: urged audience members to apply a version of this secret Audrey Gordon, Esq., Executive Director Liza Morris, Chair sauce to their own personal obstacles; her ingredients are Kyra Johnson, Clinical Trial Coordinator/ Scott D. Berns, MD, MPH, FAAP a reflection of all that PRF has, and will, accomplish. I asked Family Liason Leslie B. Gordon, MD, PhD her to share those words with you in this issue: Michelle Fino, Director of Volunteer Activities Mary Ellen Hackett Lynne MacKenzie, Donor/Communications Mgr. John Seng Start with a refusal to believe in the concept of Deborah MacGregor, Executive Assistant to Chapters & their Leaders: impossible. It may seem like more than you can the ED/Office Manager Gina Ragonese, Executive Assistant to the MD/ California, Terry Foose handle, but it is not. Kentucky, Tina Pickard Office Administrator Understand your enemy (Progeria) as best you can Amina Custovic, Bookkeeper/Administrative Michigan, Kristy & Joe Ratcliffe Assistant New Jersey, Barbara Batesko while conquering it. Discovering the gene allowed Ohio, Marla & Tim Halko and researchers to understand how progerin worked and what Medical Director: Heather & Ryan Kudzia Leslie B. Gordon, MD, PhD Pennsylvania, Jim Schoonover drugs might defeat it, allowing a cure to seem within reach. Corporate Officers: Southwest Michigan, Stephanie Howard Seek the truth: Take the thousands of pieces of Audrey Gordon, Esq., President Texas, Natalia Amozurrutia & Ryan Pallente information and gain clarity from them to understand Carl Alviti, CPA, Treasurer Publicist: the disease better in our search for treatments and cure. Barbara F. Gordon, Esq., Clerk Spectrum Science Communications, Board of Directors: Washington, DC Each grain of sand is a part of the larger picture, and you Scott D. Berns, MD, MPH, FAAP, Chair Legal: never know what that picture is until you dive in and Carl Alviti, CPA Karen N. Ballack, Esq. understand what’s going on. With Progeria, it’s the Karen N. Ballack, Esq. Weil, Gotshal & Manges, LLP, connection to aging – we are informing the aging field in Roger Berkowitz Silicon Valley, CA and NY, NY Sandra Bresnick, Esq. Sandra Bresnick, Esq. ways no one ever thought of, and vice versa. John Marozzi Quinn Emanuel Urquhardt Remain laser focused on what matters most; the Larry Mills & Sullivan LLP, NY, NY Kim Paratore children. Thinking about them every day keeps us on John Seng Accounting: track. And the most effective way to stay laser focused is Carl Alviti, Matrix Financial, LLC, Board of Advisors: Wellesley, MA collaboration; we are much better working together than Monica Kleinman, MD we could ever be working alone. Rabbi Harold Kushner Web Site: Suzette Kushner, MS Karen Gordon Betournay Coordinator Maintain a healthy dose of discontent: the successes George M. Martin, MD Useful Studios Technical/Design (gene discovery, treatment) give us momentum and Robert K. Morrison Graphic Designers: a way to push the work forward to where we must go, Elizabeth Nabel, MD Melanie Hoffman but it’s never good enough until it’s the cure. Bob Schwartzberg, CFRE Brandnu Marketing, Ambassador Family: Flower Mound, TX Love is the most important ingredient. It threads Marie Migliaccio, Topsfield, MA Brandon, Tina, Brittany and Zach Pickard through every one of the other ingredients. The Julie Pritchard Medical Research Committee: JCR Design, Foxboro, MA children are inspiring, reaching into everybody’s heart and Bryan P. Toole, PhD, Chair Regina Printing, Belleville, NJ minds so everyone will do their very best when working Christine Harling-Berg, PhD to to save children with Progeria. W. Ted Brown, MD, PhD Progeria is a fatal, “rapid aging” Judith Campisi, PhD All of you contribute to this recipe that drives PRF’s quest disease that afflicts children, Thomas W. Glover, PhD for the cure. Thank you for helping to make that effort – Leslie B. Gordon, MD, PhD who die of heart disease at an and the tremendous strides we’ve made thus far – possible. Monica Kleinman, MD average age of 14 years – the Tom Misteli, PhD same heart disease that affects Together, we WILL find the cure! Frank Rothman, PhD millions of normal aging adults. Development Committee: John Marozzi Because of Progeria’s Kim Paratore John Seng connection to general heart Audrey Gordon, Esq. disease and aging, what we learn President and Executive Director from Progeria research has the 2 potential to benefit all of us. *To view the entire talk, go to www.progeriaresearch.org/tedx In Loving GoneMemory... from our sight, but never our memories ~ Gone from our touch, but never our hearts. We have lost a dear friend to the Progeria community in Bill Sample, founder of the Sunshine Foundation and Progeria reunions. Sam, 17 years old, from the US Teresa, 15 years old, from Italy 3 Study Finds Trial Medications Increase Lifespan for Children With Progeria The best news yet… In 2012 the first trial results showed us that the farnesyltransferase inhibitor (FTI) lonafarnib helped the children gain additional weight, improve bone structure and/or, most importantly, experience increased flexibility of blood vessels Gordon( et. al., PNAS, October). In 2013, we saw evidence that lonafarnib may decrease stroke, headache and seizure rates (Ullrich et al., Neurology). Now, in 2014, 6 years have passed since the children began taking the drug, and we are beginning to see what we had hoped for: that those improvements may translate into longer lifespan (Gordon et al., Circulation). The new study shows a statistical estimate of 80% reduction in risk of death for children on treatment, and an average estimated survival increase of 1.6 years within the 6 years of treatment. There were 21 deaths in untreated versus 5 deaths among treated children. Time will tell if the estimated life extension is longer than 1.6 years. Study researchers will re-evaluate survival extension several years from now, and ask whether that number can be increased after children are on the drug for a longer period of time. The study notes that the two additional drugs added later as part of the July 2007: Sammy arrived March 2014: Zoey PRF-funded “Triple Trial”, pravastatin and zoledronate, may also contribute from Italy to enroll in the undergoes testing at to this finding. However, because lonafarnib is the drug to which everyone 1st-ever Progeria clinical drug her recent clinical trial. Here he is pictured here trial visit to Boston was exposed, and it has shown cardiovascular benefit in Progeria, it likely taking the FTI lonafarnib for Children’s Hospital plays the biggest role in increased lifespan. the first time. Collaborating For Success… The study, published in the American Heart Association’s premier journal Circulation,* was a collaborative effort between The Progeria Research Foundation, Brown University Center for Gerontology and Healthcare Research, Hasbro Children’s Hospital, Boston University and Boston Children’s Hospital. PRF’s International Registry was essential to this study, as it tracks the Progeria population Our History, worldwide over time in a confidential manner. Our Future... *Impact of Farnesylation Inhibitors on Survival in Hutchinson-Gilford Progeria Syndrome, In just 15 years, PRF has driven the Leslie B. Gordon, MD, PhD, Joe Massaro, PhD, Ralph B. D’Agostino Sr., PhD, Susan E. research that discovered the gene, Campbell, MA, Joan Brazier, MS, W. Ted Brown, MD, PhD, Monica E Kleinman, MD, treatments and now life-extending Mark W. Kieran MD, PhD and the Progeria Clinical Trials Collaborative; Circulation, treatment. Together, we will keep May 2, 2014 (on line). pushing forward in our quest to A link to the full article and PRF’s press release containing more details of study design find the cure.Thank you for and findings can be found atwww.progeriaresearch.org making this remarkable progress possible! “This is the first study to assess whether treatments influence patient survival, and thanks to a robust PRF registry and the clinical trials, we have been able to conclude that lifespan 2003: Gene Discovery extension is possible for children with Progeria” 2007: First Trial - Leslie Gordon, MD, PhD, lead author of the study, and Medical Director for PRF.
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