In April, more than 30 world leaders in Parkinson’s disease (PD) research gathered in New York City for The Michael J. Fox Foundation’s (MJFF) annual Scientific Advisory Board (SAB) meeting.  A top theme throughout the two-day meeting: the genetics of Parkinson’s disease.

Genetic research holds critical potential to help all people living with PD, whether or not they carry mutations in genes linked to the disease. By studying the biological processes underlying inherited forms of Parkinson’s, scientists can better understand all forms of the disease (familial and the more common sporadic), opening new avenues to therapeutic development.

“New understandings of the genetics of Parkinson’s disease are informing PD drug development today,” said MJFF CEO Todd Sherer, PhD. “Our Foundation is building on these discoveries to define this research and ensure its translational focus, in order to speed its practical impact for people living with PD.”

SAB members discussed the growing role of the Foundation in driving forward research into four specific genetic targets relevant to PD: LRRK2, alpha-synuclein, tau, and GBA. MJFF is devoting the lion’s share of its gene-based investments to two of these targets: LRRK2, the most common genetic contributor discovered to date, and alpha-synuclein, whose clumping is seen in every case of PD.

A clear message from the SAB was the impact MJFF could make in bringing together patients and their doctors in the quest to understand PD genetics.

“It’s important that the Foundation, and other stakeholders, try to bring their resources to bear on getting geneticists interested in PD research onto the same page and into the same room as neurologists who see patients,” said SAB member Mark Cookson, PhD, of the National Institute on Aging. “It is critical that these groups talk early and often about the next steps in genetic analysis and, in the longer term, in moving from genetic discoveries to practical treatments for Parkinson’s disease.”

Read on for the latest in how the Foundation is working to bring findings from genetics closer to pharmacy shelves. Continue reading “New Understandings of the Genetics of Parkinson’s Disease Inform Drug Development Today” »

It’s long been understood that the motor symptoms of Parkinson’s disease (PD) stem from a loss of dopamine-producing cells in the brain.

But the past few years have added weight to an emerging hypothesis in the field: that the central nervous system (CNS) disorder may in fact have its origins in a place that is far from the brain, both in distance and prestige  — the intestine.

With Michael J. Fox Foundation (MJFF) support, Berwyn, Pennsylvania pharmaceutical company QR Pharma is running with this idea, and building on their own work suggesting a gastrointestinal connection to Parkinson’s.  They hope to develop their compound Posiphen, and its ability to target and break up clumps of alpha-synuclein in nerve cells in both the brain and intestine.  Continue reading “QR Pharma Has a Gut Feeling about Parkinson’s” »

The exact cause of Parkinson’s disease is unknown, although research points to a combination of genetic and environmental factors. Genetic targets allow scientists to study important mechanisms underlying disease onset and progression for everyone, not just those with genetic mutations implicated in PD.

Genetic research is critical to increasing understanding of PD, and developing breakthrough treatments for the disease.  Specific studies focused on genetic targets like alpha-synuclein, a protein whose clumping is the pathological hallmark of PD, and LRRK2, the most common genetic contributor discovered to date, could speed progress toward treatments for everyone with PD, not just those with genetic mutations. Continue reading “Genetics and Parkinson’s: Efforts to Study the Role of Genetics in PD” »

This week, the MJFF research staff reflected on some of the projects they worked on in 2011 that they believe could have the greatest impact on the Parkinson’s disease (PD) patient community.  Read on to find out directly from Foundation team members about some of the work being done to speed progress toward a cure.

“I’m enthusiastic about the progress made in 2011 on PPMI.  The study has now enrolled over 280 individuals to participate in the study, and data have been already downloaded more than 4,000 times by scientists in the research community at large to conduct independent studies toward verifying biomarkers for PD.   MJFF also helped make a specific lab test available to researchers that could help to measure the protein alpha-synuclein as a potential biomarker for the disease – a huge step forward.  Thanks to such advancements, I am hopeful that PPMI will in the future have a major impact on drug development for PD, tangibly benefiting those living with the disease.” – Mark Frasier, PhD, director of research programs

Continue reading “MJFF Research Staff Reflects on Some of 2011′s Big Impact Projects” »

Today, MJFF awardee ProteoTech, Inc., a privately held biotechnology company, announced a funding agreement with GlaxoSmithKline (China) R&D Company Limited (GSK) to collaborate on ProteoTech’s therapeutic program targeting alpha-synuclein, whose clumping is the pathological hallmark of Parkinson’s disease (PD).

ProteoTech is the latest Foundation awardee to have announced follow-on funding deals with big pharma and venture capital firms, proving that early investment at the pre-clinical research stage does in fact expand investment in PD drug development, which in turn can accelerate promising targets to the clinic.  Other MJFF awardees to announce additional funding deals this fall include AFFiRiS, Signum BioSciences, and Sapiens Pharmaceuticals.

ProteoTech’s alpha-synuclein therapeutic research program was provided over a four-year period from 2005 to 2009 by MJFF through a $3.1 million grant under the Foundation’s Linked Efforts to Accelerate Parkinson’s Solutions (LEAPS) program. LEAPS provides multi-year, multi-million-dollar awards to help de-risk industry investment in PD, speeding progress toward treatment breakthroughs that will tangibly benefit the millions living with the disease. With MJFF funding, ProteoTech developed several promising small molecule compounds, one of which has been shown to reduce alpha-synuclein aggregates in the brains of a pre-clinical model of PD.  Additional pre-clinical studies are ongoing, as researchers work to fully understand the compound’s mechanism of action ahead of anticipated clinical trials.

Read more about AFFiRiS’ MJFF-funded work on a Parkinson’s disease vaccine

Read more about Signum BioSciences’ MJFF award targeting alpha-synuclein

Read more about Sapiens’ MJFF-funded study on Deep Brain Stimulation

This past October, Austrian biotech AFFiRiS announced $1.5 million in funding from MJFF for an early stage clinical trial of a first-of-its-kind vaccine approach to treating Parkinson’s disease (PD), called PD01.  Then, in November, the company announced 30 million Euros in additional funding from two investors to develop its portfolio of PD and Alzheimer’s vaccines.

In this podcast, Dave Iverson speaks with AFFiRiS’ Chief Medical Officer Achim Schneeberger about  PD01, and how it could work to break up the clumps of the protein alpha-synuclein that occur in the brains of those with PD.  The hope is that, in so doing, the treatment could modify the course of the disease itself.

A PD Vaccine Approach

In this first edition of “The Sherer Report,” which will become an ongoing series, Todd Sherer, PhD, MJFF CEO, highlights recent developments in three of the Foundation’s high-priority research areas, which hold clear implications for those living with PD today.

New Approaches to Treat Symptoms

Many of the motor symptoms of Parkinson’s result from a decrease in dopamine, a brain chemical that helps control movement, balance and walking. For the last 40 years, nearly every treatment for PD, including the currently available medications Sinemet, Mirapex, Azilect and Stalevo, have focused on attempting to replace this lost dopamine.

However, new lines of research are developing PD treatments based on different mechanisms that target brain chemicals other than dopamine. These approaches could replace or supplement existing therapies, limiting side effects such as dyskinesias, the uncontrollable movements that are a common side effect of existing PD drugs, while targeting some of the currently untreated symptoms of PD. Continue reading “The Sherer Report” »

In the fall 2011 issue of our newsletter, Accelerating the Cure, Nate Herpich, MJFF’s associate director of research communications, provided updates on some of our funding, including: drug repositioning, a potential PD vaccine and PPMI. Check out the newsbriefs below or click here to read the rest of the fall issue.

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RESEARCH NEWSBRIEFS

Reducing the Drug Development Timeline: Repositioning RFA

Over the past year, The Michael J. Fox Foundation has ramped up its interest in repositioning. This is the process of testing a drug that is already FDA-approved or that has been proven safe in a clinical trial for a certain indication, to determine whether the drug might be efficacious in the treatment of another therapeutic area, like Parkinson’s disease (PD). “Repositioning can drastically reduce the timeline for getting a drug into clinical testing for PD, making an impact on patients’ lives that much sooner,” says Kuldip Dave, PhD, associate director of research programs at MJFF.

While MJFF has supported repositioning projects before, its first-ever repositioning specific Request for Applications (RFA) launched in fall 2010. MJFF announced the results of this RFA in July: six researchers with awards totaling $2.4 million. Three additional awards were granted in August through other programs, bringing the total funding for repositioning to $3.4 million. Several of the research teams are working with drugs that could offer protection to the brain cells that die in Parkinson’s disease, including a tuberculosis vaccine and the antidepressant duloxetine (marketed as Cymbalta). Others are testing symptomatic therapies, including a compound used to treat Attention Deficit Hyperactivity Disorder (ADHD).

A Potential Vaccine to Slow Parkinson’s Disease Progression

This summer, MJFF awarded funding for a first-of-its-kind therapeutic approach to Parkinson’s disease: a vaccine targeting alpha-synuclein, a protein implicated in Parkinson’s disease. The vaccine aims to slow or stop the progression of Parkinson’s, something no current treatment can do.

Vienna, Austria-based company AFFiRiS AG will conduct a clinical study of the safety and efficacy of its vaccine candidate PD01. The hope is that this agent will simulate the production of antibodies that bind to alpha-synuclein, clearing it from the brain and slowing disease progression. Alpha-synuclein is a high-priority target for MJFF, largely because there is compelling evidence that it may play a role in both genetic and idiopathic cases of PD. It is also the major component in the Lewy bodies that are the pathological hallmark of Parkinson’s.

The trial, led by AFFiRiS chief medical officer Achim Schneeberger, MD, will engage 24 subjects with mild Parkinson’s disease over two years at a single clinical site in Austria. “Cautious optimism is called for,” says Jamie Eberling, PhD, MJFF’s associate director of research programs, “but it’s important to bear in mind that PD01 is still in the early stages of clinical testing.”

On the Path to Finding Biomarkers: PPMI Update

Since MJFF launched the Parkinson’s Progression Markers Initiative (PPMI) more than a year ago, the project has grown in scope, and it continues to expand its presence across the United States and Europe. Nine industry funders, including leading pharmaceutical and biotech companies, have partnered with MJFF to support this work, and researchers and clinicians across the world have begun to analyze the data and biological samples that could unlock clues to the onset and progression of Parkinson’s disease. In a move to make PPMI a truly global study, in August MJFF announced a collaboration with the Shake It Up Foundation Australia to bring PPMI down under, increasing our chances to quickly identify universally relevant biomarkers.

Of 21 planned clinical sites in the United States and Europe, 19 are now active, with two more in the EU set to begin enrolling participants soon. 179 individuals are actively enrolled at PPMI sites, including 101 newly diagnosed PD participants, and 78 control participants who do not have PD. Another 45 volunteers are pending enrollment. Samples and data collected in PPMI are available to the scientific community at large in real time for promising biomarker validation studies. Scientists using the initiative’s resources agree to report back to PPMI with findings and data, enabling future researchers to build on their work to help speed promising PD biomarker validation efforts worldwide.

You, too, can help with these efforts. PPMI continues to recruit and must find at least 400 people who are newly diagnosed with PD, and 200 controls. If you or someone you know might want to participate in PPMI, visit www.michaeljfox.org/PPMI to learn more about our study and find the nearest site.