It's been less than a year since Jonathan Silverstein, a venture capitalist at health-care fund OrbiMed, received the diagnosis that changed everything.
Parkinson's disease at age 49. A potentially more aggressive, inherited form, driven by a mutation in a gene called GBA. It affects up to 10 percent of Americans with Parkinson's, and — as for other forms of the neurodegenerative disease — there is no cure, or even treatments that slow its course.
In recent months, Silverstein and his wife, Natalie, set up the Silverstein Foundation, raised $6 million from donors and gave $10 million of their own money to fund half a dozen promising projects and start a new company.
"I'm a venture capitalist, and what a venture capitalist is, is a problem-solver," Silverstein said from OrbiMed's New York offices. "This was a problem that was not just impacting me, but another 100,000 people around the globe."
His nonprofit foundation has three main goals: first, find a way to halt progression of Parkinson's with GBA. Next, identify a regenerative approach to repair the damage it wreaks. And finally, find a way to prevent it altogether.
Accomplishing even just the first would be to do something that's never been done. Despite years of effort and capital — from the Michael J. Fox Foundation for Parkinson's Research to funding from Google founder Sergey Brin — treatments for Parkinson's disease have remained as elusive as those for other devastating neurodegenerative conditions, like Alzheimer's.
"It has been extremely challenging, and many clinical trials have failed," said Dr. Dimitri Krainc, chairman of the department of neurology and director of the Center for Rare Neurological Diseases at Northwestern University Feinberg School of Medicine. "However, we have learned important lessons from these failures."
The disease was first described two centuries ago, in 1817, by British surgeon James Parkinson. In a document he called "An Essay on the Shaking Palsy, " Parkinson described a condition characterized by "involuntary tremulous motion, with lessened muscular power."
We know now that Parkinson's results from loss of brain cells, including those that produce the chemical messenger dopamine, important for coordinating movement. Treatments have been developed to provide symptomatic relief, such as levodopa, which helps replenish the brain's supply of dopamine, but those have a set of problems of their own. Over time, people gradually need to increase the dose, and the medicines can lead to involuntary movement called dyskinesia.
The bigger problem, though, is that levodopa and other approved agents aren't neuroprotective, said Krainc, "meaning that they do not prevent neurons from degenerating."
Recent advancements in genetics provide some hope for better drug targets — including, according to Krainc, for the kind of Parkinson's that Silverstein has, driven by a mutation in GBA.
The GBA gene is responsible for creating a protein known as GCase, or glucocerebrosidase, important for helping clear junk out of cells. And work is underway already: A clinical trial from Sanofi's Genzyme unit is ongoing, and, in January, drugmaker Allergan bought an exclusive option to acquire a company called Lysosomal Therapeutics, whose lead program also focuses on GBA-associated Parkinson's. Krainc is a co-founder of Lysosomal Therapeutics and chairs its scientific advisory board.
"There is a real need for disease-modifying treatment," Allergan CEO Brent Saunders told CNBC.
Silverstein said he hopes the most advanced drugs will be able to help him, but he doesn't plan on depending on them. After his diagnosis, he sent out a massive call for any work in Parkinson's with GBA.
"We were just floored with the response," he said. Hundreds of ideas flowed in — "some of them a little bit crazier than others" — but about 80 he deemed worth looking at more closely.
Since then, the Silverstein Foundation has made six funding grants to academic labs and private biotech companies, and received a $5 million donation from drugmaker Celgene.
Being a patient as well as a venture capitalist has changed Silverstein's approach.
"As a venture capitalist, your first boss is your investors, so returns are the first thing that you have to be focused on," he said.
That can lead to less risk-taking than might lead to bigger advances.
"But when you're a patient, you come at it from a completely different viewpoint," Silverstein said. "You're not interested in incremental change. You're interested in cures."
Wednesday, along with OrbiMed and gene therapy biotech RegenXBio, the foundation announced the launch of a new company called Prevail Therapeutics. The founders of rare-disease drug giant Alexion, Leonard Bell and Stephen Squinto, are joining the board.
Silverstein knows firsthand the odds, and the timelines of traditional drug development are stacked against him. It's estimated only 1 in 10 experimental compounds that enter human trials make it to market, and it takes years to get through the FDA approval process.
But a piece of advice, he said, has remained with him: "Be hopeful."
He's also determined. Julian Adams, a drug developer who met Silverstein two decades ago, recalled learning of his diagnosis and offering sympathies.
"I got this very rapid turnaround," Adams said of Silverstein's response: "'I don't need your sympathies; I need your brains and I need a cure.'"
Adams joined the Silverstein Foundation's scientific advisory board, he said, "10 seconds later."
"He's so deeply respected in his field," Natalie Silverstein, Jonathan's wife of 17 years, said from their home in Manhattan. "The rallying around him has been incredible."
One of his biggest successes, Silverstein recently recounted, is a drug called Strensiq, sold by Alexion for a rare, genetic bone disease called hypophosphatasia. He described seeing a baby, whose mother had been told she wouldn't live past a few more months, receive a dose of the medicine when she was just a few weeks old.
She's now 9, said Silverstein, who's friends with her mom on Facebook. She's "riding bikes and climbing trees and all those sorts of things."
"I've seen miracles happen," Silverstein said. "And … now I've got to create another miracle."
For more from Silverstein, read his commentary piece: We need to approach rare diseases with a hive mind to find a cure
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