RTP-based biotech firm AskBio tests a therapy that may reverse Parkinson’s disease
A Research Triangle Park biotech company has started clinical trials for an experimental gene therapy that it says could stop — and potentially reverse — the debilitating effects of Parkinson’s disease.
The therapy, designed by the UNC-Chapel Hill spin-out AskBio, seeks to save the healthy brain cells of recently diagnosed Parkinson’s patients by injecting therapeutic genes directly into the brains of patients.
AskBio says this method targets the root cause of the disease, which attacks cells in the part of the brain that controls movement, and could dramatically improve lives.
“For the first time, it might be possible to stop and reverse this degenerative disease and truly help patients with their high unmet medical need,” Wolfram Carius, head of cell and gene therapy at Bayer, AskBio’s parent company, said in a statement. “The start of clinical trials represents the beginning towards a truly breakthrough treatment option to dramatically improve the lives of patients.”
Few treatments exist today for Parkinson’s disease. For decades, patients have taken drugs that relieve some of the symptoms of the disease, but none treat the underlying cause and the treatments diminish in effectiveness over time.
Parkinson’s causes nerve cell damage in the brain
Parkinson’s disease, which affects more than 10 million people worldwide, causes nerve cell damage in the brain. The damage leads to lower levels of dopamine, a chemical that moves electric signals throughout the brain. Those signals, in turn, help control bodily movement.
Once the breakdown begins, Parkinson’s symptoms usually start with a slight tremor in the hand, but progress to involuntary movements of other limbs and body parts.
At the moment, the disease is usually treated by dopamine substituting drugs, like levodopa. But levodopa grows less effective over time and does not target the actual causes of the brain degeneration.
“We are still using the same medications that my grandfather — had he been a neurologist — would have been using,” Amber Van Laar, AskBio’s vice president of clinical development, said in an interview. “There have been a lot of new drugs that have come on the market, but that are primarily just reiterations on levodopa.”
AskBio, she said, is trying to “actually address the underlying disease mechanisms to stop disease progression and not just the symptoms that are there.”
The company’s therapy aims directly for the part of the brain that controls movement. The company’s therapy involves injecting an adeno-associated virus (AAV) carrying therapeutic genes into the brain.
AAV is used because it doesn’t cause disease in humans and does not replicate inside the body like other viruses. Its use was pioneered by UNC scientist and AskBio cofounder Jude Samulski. AskBio uses AAV for a number of experimental gene therapies, including treatments for Pompe disease, Huntington’s disease and multiple system atrophy.
AAV, once injected into the brain, delivers glial cell line-derived neurotrophic factor genes — a protein that promotes cell growth and protects dopamine.
AskBio’s Parkinson’s treatment was developed by Krystof Bankiewicz, a professor at Ohio State University, whose company, Brain Neurotherapy Bio, was acquired by AskBio last year.
Clinical trials began last year, continue for five more
The experimental procedure started Phase 1b clinical trials last year. The trials will help determine the safety of the therapy before it is expanded to larger groups of patients. Ten patients have been enrolled since last August. AskBio hopes to add two more patients to the trial, and will follow their progress for the next five years.
Previous experiments in rodents and monkeys showed the gene therapy led to better movement control, Van Laar said, though she noted that “we are limited in what we can ask from a monkey.”
AskBio is part of a multibillion-dollar bet that Bayer, the German pharmaceutical giant, has made on treatments for Parkinson’s disease. Bayer bought AskBio last year in a deal worth potentially $4 billion, The News & Observer previously reported.
Another Bayer subsidiary, BlueRock Therapeutics, recently started another Parkinson’s-focused clinical trial using stem cells.
Katherine High, president of therapeutics at AskBio, said a difference with her company’s approach is the type of patient it is targeting.
Most clinical trials, she said, enroll patients with advanced cases of Parkinson’s. AskBio’s gene therapy might work best in people who only recently were diagnosed with the disease.
That’s because it is designed to preserve the health of the brain, and to do that, it needs more healthy cells to be present at the time of treatment.
“Based on the safety data generated so far, we convinced the regulators that it was appropriate to go into patients who were earlier in the course of the disease,” High said. “Because at that point, you still have a lot more of the cells that you’re trying to rescue.”
Typically, treating recently diagnosed patients with gene therapies has been shied away from, said Van Laar. The delivery of the gene therapy requires brain surgery, which comes with its own risks.
“When you’re talking about a patient who was just diagnosed, we know we’re going to get a good couple of years with just (levodopa),” Van Laar said. “That makes it really hard to justify doing a direct brain delivery of anything.”
For brain surgery, it is ‘minimally invasive’
Van Laar notes that, as far as brain surgeries go, it is a relatively minimally invasive procedure — most people go home within a day of the surgery. “It’s a catheter: it goes in, it goes back out,” she said. “There’s no hardware left behind. That automatically reduces a lot of the risk that’s associated with this type of procedure.”
Shying away from the procedure could mean missing out on long-term progress.
“We need to try and save what’s there,” she said. “You’re kind of defeating the whole purpose of this neuroprotective strategy by trying to do this in folks where they’ve already lost more than half their brain cells.”
“We’re really trying to preserve what’s there, if not regrow (those brain cells) a little bit better,” Van Laar added, “so that we can stop disease progression and hopefully treat symptoms as well.”
High said the gene therapy trial will provide more direction for researchers whether it is successful or not.
“The people that are actively searching for treatments, even if a treatment is not successful, they typically have learned something about the disease,” she said. “... There is virtually no successful product that doesn’t build on efforts that have been going on before.”
But with the presence of a number of gene therapies in trials for Parkinson’s, Van Laar said there is “an awful lot of hope.”
“Parkinson’s is a very high hurdle for gene therapy, no question,” she said. “But I sure think the time is ripe.”
This story was produced with financial support from a coalition of partners led by Innovate Raleigh as part of an independent journalism fellowship program. The N&O maintains full editorial control of the work. Learn more; go to bit.ly/newsinnovate
This story was originally published June 18, 2021 at 1:51 PM with the headline "RTP-based biotech firm AskBio tests a therapy that may reverse Parkinson’s disease."
