Editor’s Note (June 15, 2021): Today, national science outlet STAT published a “First Opinion” piece by Ken Marek, MD, MJFF’s scientific advisor and the principal investigator of the landmark study, the Parkinson’s Progression Markers Initiative. The op-ed discusses FDA’s approval of aducanumab for the treatment of Alzheimer’s and how it is “just the beginning of a pipeline of therapies that target the underlying biology of brain disease.” Read full op-ed here.
A significant milestone in brain disease research was achieved early this week when the U.S. Food and Drug Administration (FDA) announced approval of aducanumab for the treatment of Alzheimer’s. This drug marks several important firsts for the neuroscience field:
- the first approval of a new drug for the disease since 2003,
- the first that addresses the underlying disease process,
- and the first approved based on evidence of biological changes linked to disease.
This momentum is being felt deeply across the neuroscience field — nowhere more than in Parkinson’s research, which has long benefited from learnings around therapeutic approaches and study design in Alzheimer’s. Parkinson’s is the second most common degenerative brain disease after Alzheimer’s. The two are increasingly understood to share much biological dysfunction in common (though not many outward clinical symptoms).
In clinical development since 2015, Aducanumab (to be marketed as Aduhelm) has elicited tremendous anticipation and dialogue in the researcher, physician and patient communities. Most recently, the discourse making headlines has focused on a disparity in how scientists interpret the results from the Phase III (most advanced) clinical trial. The drug showed limited symptomatic benefit to patients, but significant effect on brain cell dysfunction tied to the disease.
Aducanumab targets a protein called beta-amyloid, which behaves abnormally in the brains of people with Alzheimer’s disease, forming tangles and clumps. In clinical trials, the drug was shown to reduce these beta-amyloid clumps in the brain. FDA based its decision on this cellular change, or biomarker data, while acknowledging that more data is required to prove that the biological effects seen in brain cells ultimately improve people’s memory and thinking. The agency is requiring drug maker Biogen to complete another study to further document the connection between these biological changes and measurable clinical benefit.
Parkinson’s also is a disease tied to clumps of a protein: alpha-synuclein. The approval of aducanumab is an important one for the business of science, as it lends confidence to biotech and pharmaceutical companies investing in programs that target synuclein clumps to stop disease. This is important to patients and families because driving, sustaining and increasing investment in priority Parkinson’s drug targets is a key element in accelerating the development of breakthrough treatments. With the support of generous donors, MJFF has granted funds for hundreds of academic and industry projects to advance biological understanding and therapeutic development of alpha-synuclein. Today, more than a dozen alpha-synuclein therapies are currently in human studies, with many more following in the R&D pipeline.
“The aducanumab approval is a real signal to the research and patient communities that this protein strategy has potential to change disease course and bring new treatments to patients,” said Todd Sherer, PhD, MJFF Executive Vice President, Research Strategy. “It also reinforces what biomarkers may make possible. We have long prioritized programs toward better measures of cellular dysfunction and will continue to lead in this area to drive closer to the next-generation treatments patients and families need.”
Scientists are working urgently to develop biomarkers of alpha-synuclein, as well as other biological systems linked to Parkinson’s disease. Of note, the biomarker used in the aducanumab study, specialized neuroimaging that allows scientists to visualize amyloid in patients’ brain cells, has been a game-changer in Alzheimer’s research over the past several years. The Michael J. Fox Foundation has made it a priority to fund continued development of such imaging biomarkers for synuclein, most recently through the $10-million Ken Griffin Alpha Synuclein Imaging Competition.
In 2010, MJFF and a host of public and private partners launched the Parkinson’s Progression Markers Initiative (PPMI) study. It is modeled after the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a major public-private partnership in Alzheimer’s that gave rise to the biomarkers supporting aducanumab’s development.
PPMI today has matured into a unique global infrastructure for the pursuit of Parkinson’s biomarkers. Thousands of Parkinson’s patients and their loved ones are participating in the study, and tens of thousands more are needed. These volunteers have enabled PPMI to fundamentally change the landscape of understanding of Parkinson’s biology. The data, information and (in some cases) biosamples contributed by PPMI volunteers flows straight into researchers’ hands in real time; this already has directly led to the launch of dozens of current Parkinson’s drug trials, similar to the one that resulted in the approval of aducanumab.
PPMI is recruiting new volunteers right now. We hope you will take a short survey to see if you are eligible.