GAP-Net site, Inland Northwest Research, and GAP President, John Dwyer, talk about the Parkinson’s disease study, PADOVA, and what it hopes to achieve.
A Parkinson’s disease clinical trial is launching at 120 global sites – including Spokane – to do a broader test of an investigational drug that in an earlier phase indicated it slowed a progressive decline in motor function.
Spokane’s Inland Northwest Research is seeking volunteers ages 50 to 85 in early stages of Parkinson’s disease and on stable doses of MAO-B inhibitors or Levodopa. Called the Padova study, this Phase 2b double-blind clinical trial will evaluate safety and results of the intravenous monoclonal antibody drug prasinezumab, as compared with a placebo.
Parkinson’s, which affects about 1 million people in the U.S., is a neurodegenerative disorder that impacts predominantly dopamine-producing neurons in a specific area of the brain. Being developed by the companies Roche and Prothena, prasinezumab targets alpha-synuclein, a protein that can abnormally form clusters called Lewy bodies that are believed to be toxic and give rise to the disease. Parkinson’s symptoms include tremor, rigidity, slowness of movement and impaired balance.
In a previous Phase 2 Pasadena study, prasinezumab after a year of use “significantly reduced decline in motor function by 35%” versus a placebo and was generally safe and well-tolerated, a news release said. Researchers are hoping for the discovery of a disease-modifying drug, since the only approved medications for Parkinson’s are to treat symptoms, said Dr. Jason Aldred, a Spokane neurologist and Parkinson’s specialist.
Aldred is Inland Northwest Research’s primary investigator. “With Parkinson’s studies, we’re unfortunately accustomed to failures with many of the things we’ve tried, but this comes on the heels of the Phase 2 study showing that prasinezumab reduced decline in motor function by about 35% compared to placebo at one year, and that’s kind of exciting,” Aldred said.
“Of course, more work needs to be done to ensure it’s something down the road we’d want to use for Parkinson’s – that’s not been shown yet – but it has the potential for prasinezumab to be the first disease-modifying, alpha-synuclein antibody showing effects on multiple endpoints for people with Parkinson’s or some of the things that are important with their condition.”
Prasinezumab is designed to block the cell-to-cell transmission of the aggregated pathogenic forms of alpha-synuclein in Parkinson’s disease. Alpha-synuclein formed into a Lewy body is thought to cause some type of stress to the dopamine-producing nerve cells, Aldred said.
“Alpha-synuclein is a key part of that, and we know it forms inappropriately when it makes these Lewy bodies in Parkinson’s disease, so the idea is when someone has symptoms of Parkinson’s, there are Lewy bodies there and alpha-synuclein lumped together inappropriately,” Aldred said.
Current treatments ease symptoms, he said, but the bigger problems occur much later. Although the disease’s progression is slow, some people with Parkinson’s eventually have severe difficulties with mobility, cognitive abilities and advanced features.
“We think that happens because the alpha-synuclein in this abnormal form will spread from nerve cell to nerve cell to nerve cell and end up causing more severe, advanced features of Parkinson’s disease. The hope is prasinezumab will be able to do what we call disease modification. It would change what is currently the natural history for most people with PD.”
“With prasinezumab, we hope it binds specifically to the abnormal form of alpha-synuclein and not the normal form, so it’s specific to the abnormal chemical structure that’s harmful,” Aldred said.
There is much interest in developing immunological treatments such as this drug, if proven effective, and “using somewhat of the body’s own immune system,” Aldred said. Inland Northwest Research screened its first patient for this study earlier this month as the first site to do so worldwide.
People who volunteer in clinical trials often want to be part of a solution for current or future Parkinson’s patients, said Bob Finkbiner, 70, who has driven from Walla Walla to Aldred’s research site in Spokane to help with that cause.
Although he isn’t part of this Padova study, he’s participated in two different trials, including one recently completed with negative results. But he’s also witnessed the disease’s worsening impact among family, including a grandfather on his dad’s side and his mother.
“I’ve seen enough of Parkinson’s in my own family that if there is anything that I can do to be part of a study that would help solve some of the concerns, I’d be very happy to do that,” Finkbiner said. “When you join a study like this, it’s like you’re joining into a family almost. You get to know the people who are working with you, and you all have the same goal – to somehow be able to bring a cure to Parkinson’s or at least bring a stop to the progression.”
“There are perks. You get to see a doctor at least once a month, and you get the latest news on what’s being done for Parkinson’s. You just know what you’re doing is going to be a help to somebody, although it may not be right now, but in the future there are those who are going to benefit from what you’re helping to accomplish right now.”
The Global Alzheimer’s Platform Foundation is a nonprofit helping to accelerate the recruitment processes among its network in North America, including Inland Northwest Research. John Dwyer, the foundation’s president, said volunteers benefit from having a Parkinson’s expert such as Aldred regularly reviewing their cases at no cost to the individuals. There also are other contributions.
“The benefit can be threefold,” Dwyer said. “First, the person to be cured of Parkinson’s will be in a clinical trial, and, second, even if this research is not totally effective, Parkinson’s has a very high family correlation, so you’re helping your family and next generations even if it doesn’t help you. And, third is you’re helping society in general.”
The Padova study is expected to enroll 575 participants across eight countries at 120 sites overall. Dwyer said it would be ideal to attract more male volunteers to the trial, as well as a mix of multiracial participants.
“If somebody is in the study, they’re going to get a really terrific understanding of their condition and a shot at getting a drug that can make a difference in the rate of decline,” Dwyer said.
To learn more about the study in Spokane, contact Inland Northwest Research by emailing contact@inwresearch.com and calling (509) 960-2818. To find other research centers participating, go online to clinicaltrials.gov/ct2/, email global-roche-genentech-trials@gene.com and call (888) 662-6728.
Originally posted by The Spokesman Review on April 29, 2021.