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ACCELERATING the CURE the Newsletter for Friends and Supporters of the Michael J ACCELERATING THE CURE The newsletter for friends and supporters of The Michael J. Fox Foundation for Parkinson’s Research WINTER/SPRING 2008 $4.4 Million LEAPS Award Targets NEWS FROM Glutamate System for New Class THE CEO of Parkinson’s Therapy In December The Michael J. Fox Foundation awarded a $4.4-million LEAPS (Linked Efforts to Acceler- ate Parkinson’s Solutions) grant to a multidisciplinary team of researchers led by Jeffrey Conn, PhD, of Vanderbilt University to jump-start the development of a new class of symptomatic Parkinson’s disease In 2007 The Michael J. Fox Foundation funded about drugs targeting the glutamate system and in particular a glutamate receptor called mGluR4. $25 million in Parkinson’s research, bringing us over the $100-million mark in total research funded. Because the death of dopamine neurons is a hall- will now use a combination of medicinal chemis- While we’re proud of the momentum and targeted mark of PD pathology, Parkinson’s scientists tra- try, molecular biology, and animal studies to en- activity that figure represents, the metric we find ditionally have focused their efforts on modulat- gineer these molecules into a compound that can most meaningful is the same one you probably do: ing aspects of the dopamine system. But recent be clinically tested for use as a drug that could insights into the physiology of the basal ganglia (a provide sustained symptomatic relief. practical advances toward life-transforming treat- brain region affected in Parkinson’s disease) have ments for Parkinson’s disease. shed light on the potential for treatments that Scientists do not yet fully understand how mGluR4 could alleviate PD symptoms by “resetting” brain may work to alleviate Parkinson’s symptoms. Re- With a new year under way, we are more committed circuits. The glutamate system in particular has search to date has indicated that mGluR4 acti- than ever to doing whatever it takes to make those shown promise as a target for such treatments. vators may work by triggering a compensatory advances a reality. mechanism or process that allows the brain to “Dopamine replacement therapies have long been send messages without the use of the dopamine We’ve recently announced over $8 million in funding considered the ‘gold standard’ of Parkinson’s receptors that die in Parkinson’s disease. for two LEAPS projects aiming to establish entirely treatment. But they lose efficacy over time, allevi- new classes of PD therapies. You can read more about ate only some of PD’s symptoms, and cause side The Business of Glutamate effects that can be as debilitating as the disease Also in December, news media reported that one of them at left. See pages 2 and 3 for informa- itself,” said Katie Hood, CEO of MJFF. “Patients two pharmaceutical companies, Addex Phar- tion on our $2-million partnership with Merck Serono don’t think this status quo is good enough, and maceuticals and Merck & Co., Inc. (through its (EMD Serono in North America) to forge new treat- neither does our Foundation. Dr. Conn and col- affiliate Merck Sharp & Dohme Research Ltd.) had ments for those afflicted by PD-related cognitive and entered a collaboration and licensing agreement leagues are aiming to bring about a 180-degree mood disorders, and to read a Q&A with an expert on turn in PD treatment by developing an entirely to develop a drug targeting mGluR4. the surprisingly common (and potentially debilitat- new class of drugs that would bypass the dop- “The news of the Merck-Addex collaboration is ing) cognitive effects of Parkinson’s disease. And see amine system altogether.” very positive for us and our mGluR4 project,” said pages 6 and 7 for Foundation news and stories of In addition to Dr. Conn, the multidiscliplinary Dr. Conn. “It will help stimulate activity in the Team Fox members and other friends who continue to area and could potentially drive interest from oth- team of principal investigators comprises C. Da- apply limitless ingenuity and generosity to the fight er drug companies in developing the compounds vid Weaver, PhD; Colleen Niswender, PhD; Carrie for a cure. K. Jones, PhD; Yoland Smith, PhD; and Craig W. that will come out of our program. Pharma tends to follow its competition, so seeing Merck get into Lindsley, PhD. All sit on the faculty of the Vander- No matter what we take on, we focus on one key ques- bilt Program in Drug Discovery, with the exception this area will make others want to do the same.” tion: How will this impact the lives of people with PD? of Dr. Smith, of the Yerkes National Primate Re- About LEAPS search Center. Your friendship makes that focus possible. Together, LEAPS are multi-year, multi-million, multi-dis- I know, we’re creating a future where Parkinson’s dis- What Is mGluR4? ciplinary projects that bring together “all-star” ease is only a memory. Glutamate, like dopamine, is a neurotransmitter teams of researchers to address questions with — a signaling molecule that plays a role in trans- significant practical impact on the treatment of porting brain messages and controlling body func- Parkinson’s disease. Continued funding is depen- tions. Dr. Conn has shown in an animal model that dent on completion of predetermined milestones increasing activity of a specific glutamate recep- at specific stages. tor, mGluR4, may alleviate symptoms of Parkin- More information on this and other LEAPS awards, Katie Hood son’s. In further work supported by MJFF’s Target including grant abstracts and researcher bios, is available Chief Executive Officer Validation initiative, his team identified molecules at www.michaeljfox.org. that increase mGluR4 activity. The researchers PAGE 2 MJFF partners with Merck Serono to “invigorate research and therapeutic development” IN THIS ISSUE for PD-related cognitive disorders PAGE 3 David Weiner, MD, talks to MJFF about PD-related cognitive dysfunction PAGE 5 Irene Hegeman Richard, MD, appointed Senior Medical Advisor to MJFF RESEARCH NEWS MJFF Partners with Merck Serono to “Invigorate Research and Therapeutic Development” for PD-related Cognitive Disorders In December the Foundation committed up to cognitive and psychiatric symptoms, simple ex- test cognitive dysfunction as a risk marker or po- $2 million for research toward therapies to trapolation of this knowledge to Parkinson’s is not tential biomarker of Parkinson’s disease. possible — perhaps due to the pathology of PD alleviate Parkinson’s-related cognitive dysfunc- and its treatments.” In selecting research projects for Cognitive Deficits tion and mood disorders. Funding for the Cogni- and Mood Disorders in Parkinson’s Disease, MJFF Dr. Sherer noted that MJFF and Merck Serono hopes to address several cognitive issues, which tive Deficits and Mood Disorders in Parkinson’s hope, through their innovative partnership, to en- include better understanding the pathophysiology Disease initiative was made possible by gener- courage Parkinson’s scientists to collaborate with of cognitive disorders, validating tools to predict ous leadership funding from Merck Serono (EMD researchers from other areas, including psychia- or assess early development of cognitive dysfunc- try, in order to capitalize on work already done and tion and evaluating the impact of existing PD Serono in North America), affiliates of Merck to obtain different perspectives on cognitive and treatments for these symptoms. KGaA, Darmstadt, Germany. psychiatric disorders in Parkinson’s disease. Elmar Schnee, president of Merck Serono, com- “Most people think of Parkinson’s disease as a While MJFF has funded research focused on cog- mented: “Merck Serono recognizes the urgent motor disorder, but time and again, patients tell nitive dysfunction before, this initiative is the need for new therapies to alleviate PD-related us that the cognitive and mood-related symptoms Foundation’s first exclusively dedicated to this mood disorders and cognitive dysfunction, and of PD — including depression, anxiety and execu- research area. Previous grants have examined we look forward to supporting The Michael J. Fox tive dysfunction — are some of the most disabling aspects of the disease,” said Katie Hood, the Foundation’s CEO. “These symptoms frequently affect patients early in their disease and don’t “Most people think of Parkinson’s disease respond to dopamine replacement therapy. With the Cognitive Deficits and Mood Disorders in Par- as a motor disorder, but time and again, kinson’s Disease initiative, we hope to invigorate patients tell us that the cognitive and research and therapeutic development in this very important area.” mood-related symptoms of PD — including Cognitive dysfunction, which includes difficulty depression, anxiety and executive in planning, sequencing, initiating and sustaining behavior toward a given goal, and incorporating dysfunction — are some of the most feedback to make adjustments along the way, is estimated to occur in up to 80 percent of people disabling aspects of the disease.” with PD. Depression is thought to affect up to 50 percent of Parkinson’s patients. Anxiety and apa- — Katie Hood thy also are often associated with PD. “While treatments for classic forms of depres- aspects of cognitive dysfunction including acetyl- Foundation in pursuit of effective treatments for sion or anxiety have been developed, little evi- choline deficiency, which has been linked to cog- these under-addressed aspects of Parkinson’s dis- dence exists that they are optimal when used in nitive problems like concentration and executive ease. Our support of the Foundation is just one Parkinson’s patients,” said Todd Sherer, PhD, the functions, and approaches designed to test wheth- example of our commitment to driving the innova- Foundation’s vice president, research programs. er behavioral interventions can target the everyday tive science that will allow every individual to live “Additionally, while information from other fields action impairment that characterizes PD-related a fuller and more satisfying life.” must be leveraged in pursuing treatments for PD’s dementia.
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