By Todd Sherer, PhD
Chief Executive Officer, The Michael J. Fox Foundation for Parkinsonís Research
As a scientist and CEO of The Michael J. Fox Foundation (MJFF), I keep a close eye on all of the latest news in Parkinsonís disease (PD) research. As we approach the year end, Iíd like to share my insights with you on the current state of the field ó where weíve made critical strides in PD research and where challenges remain. In particular, I want to highlight recent developments that hold clear implications for those living with PD that fit into two of the Foundationís priority research areas: (1) Novel approaches to treat symptoms of PD and (2) translating increased understanding of what causes PD into new therapies. As you will learn below, many of these advances are in the clinic and recruiting PD and control volunteers just like you. And, given the projects going on, now could not be a more exciting time to participate in PD research.
Novel Approaches to Treat Symptoms
Many of the motor symptoms of Parkinsonís 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. I believe that several non-dopamine-based approaches have the potential to tangibly impact patientís lives. Research underway that is promising includes:
- Swiss biotechnology company, Addex Pharmaceuticals, launched a clinical trial last spring to target the neurotransmitter glutamate. Similar to dopamine, glutamate is responsible for transporting brain messages and controlling body functions. The hope is that, by bypassing the dopamine system altogether, it might be possible to provide the same symptomatic benefit of levodopa without triggering adverse effects such as dyskinesias. Addex is studying how limiting the activity of a particular glutamate receptor called mGluR5 could reduce these dyskinesias.
- Significant evidence also exists to support the development of therapies targeting another glutamate receptor, mGluR4. Last summer, Jeff Conn, PhD, of Vanderbilt University announced that his team was ready to declare drug candidate status on three compounds that act on mGluR4 as an alternative treatment for PD.
While there is no guarantee that any of these therapeutic strategies will ultimately be successful, for the first time in years, several approaches focused on novel biology are now in late-stage drug development for Parkinsonís. New hypotheses provide the opportunity for dramatic progress toward new treatments for PD.
Translating Increased Knowledge of a Cause into Therapies
Thanks to improved technology and significant research investments over the past decade, scientists are homing in on genetic contributors to PD. Identifying genetic factors that cause or increase the risk for Parkinsonís is the first step toward converting this information into new treatment strategies. Recently, scientists have build upon recent genetic findings that could open new avenues toward disease-modifying treatments ó the most significant unmet need of Parkinsonís patients. Advances in this area include:
- The alpha-synuclein gene plays a critical role in PD. Scientists at Austrian biotech AFFiRiS are working on new ways to target this gene and its protein product, whose clumps ó known as Lewy bodies ó are the pathological hallmark of Parkinsonís. AFFiRiS is launching the first-ever PD vaccine clinical trial. The study draws on evidence from pre-clinical studies that suggest their vaccine helps clear clumps of alpha-synuclein from the brain, potentially slowing disease progression. If successful, this could lead to a breakthrough in how we treat PD. Similar approaches to Alzheimerís disease are also progressing through the therapeutic development pipeline.
- Mutations in the gene LRRK2 are the most common genetic cause of PD discovered to date. LRRK2 is a high-priority research area for MJFF, and weíre tackling it from multiple angles simultaneously to accelerate progress. On one front, MJFF-funded researchers in our 30-lab LRRK2 Biology Consortium are working quickly to advance knowledge of LRRK2ís structure and function in the cell to speed development of practical treatment strategies. Consortium members at Harvard University discovered a compound that blocks the action of LRRK2 ó a prototype for a potential future treatment. This compound is now being shared with LRRK2 researchers around the world. A University of Ottawa lab in the consortium is studying how LRRK2 may influence immune system response to external triggers of PD, which could establish a link between environmental and genetic causes of Parkinsonís disease. Complementing these efforts is MJFFís LRRK2 Cohort Consortium. Through this initiative, eight research groups are systematically studying more than 3,000 people with and without PD who carry mutations in the LRRK2 gene in order to understand the clinical features of LRRK2 Parkinsonís and how they may respond to future treatments.
As you know, MJFF shares the goals of Parkinsonís patients and their loved ones: To accelerate the delivery of therapeutic breakthroughs, and, ultimately, a cure. Increased recruitment for clinical trials is vital to reaching conclusive results quickly in order to speed new treatments toward pharmacy shelves. You play a critical role in making all PD research a success. Your profile on Fox Trial Finder and willingness to participate in trials will help us find the answers we need. On behalf of MJFF, I deeply appreciate your contributions.