Because Parkinson’s disease comes in many different forms, the condition is an especially difficult target for drug development. But a new grant from the Michael J. Fox Foundation for Parkinson’s Research has spurred Octave Bioscience to take on the challenge.
Parkinson’s affects nearly a million people in the U.S., and while individual patients share a diagnosis, their experiences are often unique. The progression and severity of the illness vary, as do its broad constellation of motor and non-motor symptoms. While one person may have severe memory or cognitive symptoms with mild tremors, another may have severe tremors and few brain-related symptoms.
Drug responses don’t follow a predictable path for people with the disease, which experts say is likely driven by an interplay of genes and environmental factors.
William Hagstrom, CEO and founder of Octave, a commercial-stage precision medicine solution company, believes a more nuanced understanding of these complexities is crucial to better outcomes. The Michael J. Fox Foundation recently gave the company a $10 million grant to do what it has already done for multiple sclerosis (MS) — create a custom protein biomarker panel to measure disease activity and progression. The bespoke diagnostic could accelerate a needed shift toward a precision-medicine approach for the disease and help researchers find more effective drugs for a market expected to reach $10.4 billion by 2031.
Why biomarkers matter
The Michael J. Fox Foundation has raised more than $1 billion in its push toward a cure and recently celebrated the discovery of a Parkinson’s biomarker test to detect alpha-synuclein, an abnormal protein that clumps in the brains of people with the condition.
To further advance biomarker development, the foundation chose Octave because the company created a blood diagnostic called the Multiple Sclerosis Disease Activity (MSDA) test that measures 18 biomarkers, providing a snapshot of disease activity.
“We think there’s a dramatic shift coming to the market, which is largely dominated today by drugs for symptomatic relief."
CEO, founder, Octave Bioscience
“It produces a quantitative score on a scale of one to 10 where physicians can look at baseline in a patient pre-therapy, post-therapy, response-to-therapy, relapse, and so forth along the way,” Hagstrom said. “It got a lot of attention in the field.”
The company will now develop a similar test for Parkinson’s. Hagstrom said Octave had already planned to move into the Parkinson’s space — and eventually Alzheimer’s and amyotrophic lateral sclerosis — but the opportunity to work with The Michael J. Fox Foundation accelerated their timeline.
“These are complex, high-cost diseases with typically tragic outcomes and they tend to be poorly characterized on specific measures, so they are wide open for a precision-care solution,” Hagstrom said.
Parkinson’s is particularly challenging because it’s typically preceded by a prodromal phase, marked by symptoms such as constipation, loss of smell, sleep problems and depression that can last for 15 to 20 years.
“Unfortunately, by the time there’s a diagnosis, there might be 60% to 80% loss of dopaminergic neurons,” Hagstrom said. “Earlier diagnosis of differential is certainly important to the field clinically. It’s also important from a pharma drug development perspective.”
Another priority is to develop a test that can take into account all the systems involved in Parkinson’s, from neuroinflammation and microglial activation to alpha-synuclein accumulation, Lewy bodies, neurodegeneration, synaptic dysfunction, mitochondrial dysregulation, oxidative stress and tau pathology, he said.
Parkinson’s research is moving closer to real solutions for the disease, Hagstrom believes.
“We think there's a dramatic shift coming to the market, which is largely dominated today by drugs for symptomatic relief,” he said. “Disease-modifying therapies will be transformative to the field like they have been for so many other diseases like MS or like rheumatoid arthritis.”
But first, research needs to unravel the disease’s many mysteries.
“To get drugs to market will require better endpoints,” Hagstrom said.