2017 Research Year in Review

Transcription

1 2017 Research Year in Review

2 Extraordinary trends have been evident in Parkinson s disease (PD) research for the past several years, and 2017 was no exception. The PD drug development pipeline, once stalled and slow-moving, is now abuzz with activity and investment toward a new generation of treatments with considerable implications for patients quality of life. Parkinson s patients nationwide are engaged as never before, with unprecedented opportunity to shape the future of PD research. The Michael J. Fox Foundation for Parkinson s Research (MJFF) remains determined to maintain this momentum, and looks forward to 2018 with reason for tremendous hope and anticipation. Hungry for more than we can fit here? Visit michaeljfox.org/2017inreview for in-depth information on the projects described throughout.

3 3 On the Move: Market-Bound Therapies Enormously promising drug development activity continues to unfold with new approvals and clinical trial milestones for a range of improved therapies Research Year in Review Two new Parkinson s drugs came to market in 2017, including the first drug specifically indicated for levodopainduced dyskinesia: Adamas Gocovri is an extendedrelease formulation of amantadine. MJFF enabled the drug on its path by sponsoring the development of a dyskinesia rating scale instrumental to testing the drug in clinical trials and thus attracting industry investment. The other 2017 approval was Newron s Safinamide (Xadago), an addon therapy for those dealing with persistent symptoms despite levodopa. These approvals mark a total of six new Parkinson s treatments in the past three years. The heartening expansion of treatment options is expected to continue through 2018 with the late-stage development of several novel formulations of levodopa. For years, scientists have searched for a more consistent way to get levodopa into the brain. When taken orally, absorption of levodopa into the blood and brain can be inconsistent, coming in peaks and valleys, which leads to motor fluctuations, including disabling off periods. Two MJFF-backed therapies to lessen off periods are nearing the home stretch to market. Acorda s inhaled formulation of levodopa will enter FDA review shortly; Phase III results of Sunovion Pharmaceuticals under-the-tongue apomorphine film strip are being analyzed now, with the company expected to publish findings from the trial and move toward regulatory approval in coming months. Other novel approaches to smooth out daily fluctuations are progressing, too. MJFF-funded NeuroDerm (acquired in a billion-dollar deal by Mitsubishi Tanabe Pharma Corporation in July) is conducting Phase II and III trials of under-the-skin pumps and pump-patches for continuous, transdermal delivery of levodopa. And, MJFF awardee Voyager Therapeutics reported positive Phase I results for a gene therapy approach that assists the brain in converting levodopa into dopamine for better outcomes as disease advances. Induced pluripotent stem cells (also known as ips cells engineered by reprogramming mature adult cells) might one day treat motor symptoms by replacing damaged dopamine cells. They took an important step toward clinical trials, as a research team from Kyoto University demonstrated their safety and functionality in non-human primate models of disease, opening the door to future human testing. Deep brain stimulation (DBS) surgery, while already available and appropriate for some patients, remains under active study. MJFF-funded researchers are looking for ways to expand its benefits to more individuals with Parkinson s disease. One ongoing investigation seeks to target brain areas associated with balance problems (unaddressed by current forms of DBS). Another team wants to determine whether DBS can slow symptom progression if administered in earlier stages of disease. Others are working to develop adaptive or intelligent DBS allowing for the continuous optimization of therapy on an individual basis, maximizing motor symptom improvement and minimizing adverse effect, prolonging battery life and reducing the need for battery replacement surgeries.

4 4 The Michael J. Fox Foundation for Parkinson s Research Still Patients Greatest Unmet Need: A Cure While patients are accustomed to research ebb and flow in the symptomatic space, 2017 was different because of its correspondingly high level of activity in novel curative approaches. Several therapies that may slow or stop Parkinson s disease something no current therapy has been demonstrated to do now are in clinical trials. With support from committed donors, MJFF has allocated hundreds of millions of dollars in research funding to advance these targets. Scientists believe many of the resulting therapies will eventually treat the broad disease population, but are taking a personalized approach to early clinical trials, recruiting trial participants based on individual biology marked the first trial (sponsored by pharmaceutical firm Sanofi Genzyme) enrolling people with GBA genetic mutations linked to PD. GBA mutations, also linked to Gaucher disease, are the most common genetic cause of PD yet discovered, accounting for five to 15 percent of all Parkinson s cases, depending on ethnicity. Counteracting the dysfunction associated with GBA mutations lowered activity of the glucocerebrosidase (GCase) protein could slow or stop progression of Parkinson s disease. Genetic target LRRK2 has been the focus of intense investigation by PD researchers since the 2004 discovery of its link to Parkinson s. In 2017, this critical molecule continued its rapid (by science standards) journey toward the clinic, where first-in-human trials are expected to begin within the next several months. Also in 2017, researchers focused on key aspects of LRRK2 biology, including better characterization of LRRK2 protein s interactions with other molecules in body cells, and attempting to solve its structure an important step in therapeutic targeting. The LRRK2 protein is large, and its structure has proved challenging to solve through even state-of-the-art techniques. Microgravity conditions can be beneficial for solving the structure of challenging proteins, so MJFF partnered with NASA and the Council for Advancing Science in Space (CASIS) to send LRRK2 to the International Space Station. Our mission has grown beyond the boundaries of Earth s gravitational pull, said Michael J. Fox. In September, we learned that LRRK2 demonstrated some of the same challenges in space as on Earth. Nonetheless, the project was a success in engaging a team of world-renowned structural scientists, new to PD, now exploring a collaboration to solve the LRRK2 structure once and for all. A universal feature of Parkinson s is aggregation, or clumping, of the protein alpha-synuclein in the brains and body cells of people with the disease (similar to the amyloid clumps seen in Alzheimer s disease). No fewer than five companies are conducting clinical trials aspiring to prevent or break up synuclein clumps, which scientists believe could stop PD in its tracks. Two more companies plan to begin alpha-synuclein trials soon. MJFF has funded four of these seven projects and is working with the field at large on continual improvement of synuclein-based approaches to treat PD. (And read more on opposite page about our continuing priority to develop alpha-synuclein as a Parkinson s biomarker or test to assess risk, presence and progression of the disease.) The Foundation also is working to advance several potentially disease-modifying therapies via repurposing scientifically evaluating drugs approved for another condition for their benefit in PD. After millions in MJFF funding to launch Parkinson s-specific testing of isradipine (a hypertension drug) and inosine (an antioxidant supplement), both programs have now advanced to Phase III trials. Much promising work jump-started by MJFF is ongoing in Phase II as well: encouraging results from a trial of diabetes drug exenatide have laid the groundwork for future investigation, and a trial of cancer drug nilotinib began recruiting.

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6 6 We Will Find an Objective Test for Parkinson s Disease It is our obligation to drive toward clear outcomes from today s clinical trials. That s why MJFF is doubling down on years of aggressive support for biomarker development Research Year in Review The need for Parkinson s biomarkers (like hypertension in heart disease or blood sugar levels in diabetes) has become only more urgent as more projects march toward human testing. Now in its seventh year, the Parkinson s Progression Markers Initiative (PPMI), the Foundation s landmark global biomarker study, has enrolled more than 1,500 volunteers. PPMI has become a world model for Parkinson s study design, lending the field groundbreaking tools and insights such as the use of dopamine scans (DaTscan) as an early PD progression marker, the identification of factors that may predict cognitive decline, and even best practices in how to effectively recruit patients and controls for clinical studies (an ongoing challenge in Parkinson s research). In fall 2017, MJFF announced a new partnership with the National Institutes of Health and industry to expand on futuristic omics work (e.g. genomics and proteomics). Omics studies hold potential to define the molecular fingerprint of disease by looking inside body cells and fluids data that in Parkinson s may help scientists understand what causes PD and pursue new avenues to preventing or stopping disease. Through this program, MJFF and its public-private collaborators will fund millions of dollars for high-tech analysis that will continue to increase the utility of precious data and biosamples from PPMI and other studies. MJFF also continues its relentless pursuit of a state-ofthe-art imaging tracer tool to visualize key PD protein alpha-synuclein in the living brain, one of the field s hottest leads toward a Parkinson s biomarker. In 2017 we announced a new initiative with scientists already working on another protein, tau, in order to leverage world-class talent and existing resources to push complex imaging work forward faster. And because alpha-synuclein clumps not just in the brain but in cells all around the body, MJFF has invested nearly $6M in the Systemic Synuclein Sampling Study (S4), which finished recruitment this year and is now rapidly analyzing various fluid and tissue samples to determine the most efficient and relevant ways to measure synuclein clumping in people with PD. Your support also is helping us turn science fiction into real science. MJFF is funding studies analyzing keyboard use, microscopic eye movements and breath volatile organic compounds (VOCs) to screen for Parkinson s. We re also partnering with data scientists and movement disorder specialists to drive strategies for using PD data collected through smartwatches and smartphones.

7 7 The Michael J. Fox Foundation for Parkinson s Research You Are the Solution You Seek With Parkinson s research moving into the clinic, there has never been a more urgent need for patients themselves, and loved ones, to take part in studies that can help carry new therapies over the goal line. People with Parkinson s and their loved ones hold tremendous power to keep research moving forward in many cases, they are the only ones who can. Emerging technologies are expanding patients opportunities to report on health and treatment outcomes in order to inform scientists, regulators and payers and influence public policy. Active involvement in shaping the future of PD research means different things to different people MJFF is committed to helping everyone navigate their own road to participation. Fox Insight (foxinsight.org), the Foundation s online observational study of Parkinson s disease, officially launched in fall 2017 after two years of optimization in a beta launch phase (achieved with the help of more than 7,000 participants enrolled starting in 2015). Fox Insight collects patient-reported outcomes, or PROs critical data on the lived experience of Parkinson s disease from tens of thousands of people with Parkinson s as well as control data from people who do not have the disease. Through a partnership with 23andMe, patients can choose to contribute genetic data to be paired with PROs. All the information provided is de-identified and made available to qualified Parkinson s investigators worldwide for independent studies of PD. Meanwhile, with nearly 70,000 registrants (and counting), MJFF s online smart trial matching tool, Fox Trial Finder (foxtrialfinder.org), continues to increase the flow of willing volunteers into clinical trials. With referrals from Fox Trial Finder, clinical trials are able to find eligible volunteers faster and keep experimental treatments moving toward pharmacy shelves. We re on a mission to meet every person with Parkinson s, online or face-to-face, as part of our commitment to introduce patients and families to the robust nationwide PD community. In 2017, we restructured our staff to create a Community Engagement team dedicated to helping patients and loved ones navigate the Foundation s many opportunities to take action in research, education and advocacy. This year s Third Thursdays Webinars, moderated by veteran journalist and MJFF Patient Council Co-Chair Dave Iverson, attracted over 50,000 attendees to learn about topics of interest in Parkinson s research and care, and our Parkinson s Podcasts accumulated over 10,000 downloads. From 2014 to 2017 our Partners in Parkinson s program, a strategic research initiative with AbbVie, served nearly 16,000 patients and families in cities throughout the United States with local community resources and information about the importance of seeing a movement disorder specialist. Another 5,600 took part in Partners in Parkinson s webinars and 1,200 viewed the online video gallery.

8 Research Year in Review Voices of Policy and Advocacy MJFF s policy initiatives aim to bring the Foundation s resources and community to bear on issues that impact the lives of Parkinson s patients, families and caregivers. In February, the Foundation hosted more than 200 Parkinson s patient advocates, including Michael J. Fox, from 43 states, at its first Parkinson s Policy Forum in Washington, D.C. They held nearly 200 meetings with members of Congress, including a confab with bipartisan leadership from the House of Representatives. The goal of the Forum: bring patient advocates together for education and resource sharing to bolster advocacy in support of policies that safeguard federal research funding and access to care. Broadening the reach of the Forum to those who could not attend in person, the Foundation streamed several panel discussions live from D.C., which have received more than 45,000 views to date. Advocacy takes place throughout the year, as the MJFF community demonstrated in 2017 a year of extreme highs and lows for anyone concerned about the future of health care in the United States. Our advocacy toolkit was downloaded more than 1,000 times in less than three months. Nearly 13,000 advocates representing all 435 congressional districts across 50 states contacted their lawmakers more than 54,000 times on various policy issues affecting the Parkinson s community, including health care reform, policies impacting drug approvals by the U.S. Food and Drug Administration, and the renewed regulation of glyphosate (Roundup), a chemical known to increase risk of Parkinson s disease.

9 I look at life as endless opportunity and I wake up every day curious. I live with acceptance and not in expectation. But acceptance isn t resignation, it s just acknowledging the truth and being empowered by it. Michael J. Fox

10 The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson s disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson s today clinical trials have been supported by MJFF to date $750 million in research funded since cents of every dollar spent at MJFF goes to programming Learn more about our high-impact Parkinson s research programs. Visit us at michaeljfox.org or call PHOTOS BY SAM OGDEN