Many people with Parkinson’s disease no longer move their bodies as they used to. Your hands may tremble when you are at rest. Muscles may become stiff. You may walk more slowly and your balance may become unstable. The most effective treatment remains L-dopa, also called levodopa, a drug that can dramatically improve movement and quality of life. However, relieving symptoms often comes with caveats, as over time the drugs become less reliable and can lead to irregular, involuntary movements known as dyskinesias.
Now, researchers led by Sinopia Biosciences, a startup out of the University of California, San Diego, have reported preclinical results that could help change that equation. In animal models of Parkinson’s disease, the drug candidate, SB-0110, enhanced the effects of L-dopa while reducing the side effects of dyskinesia.
The paper is scientific translational medicine July 15th.
Virtually all Parkinson’s patients take levodopa. However, patients face two major problems with the drug: Parkinson’s disease symptoms and dyskinesia recurrence. There is no drug that can simultaneously address both in addition to L-dopa in a powerful way, and that’s what our drug candidate does. ”
University of California, San Diego alumnus Arash Boldvar, CEO, chief scientific officer, and co-founder of Sinopia Biosciences
The need is growing. The World Health Organization estimates that more than 8.5 million people worldwide had Parkinson’s disease in 2019, and the prevalence of the disease has doubled globally over the past 25 years. For many of these patients, the benefits of levodopa become difficult to manage over time. After more than 9 years of treatment, approximately 70% develop motor fluctuations (periods of symptom recurrence between doses) and approximately 90% develop dyskinesias.
Where computation and biology meet
Mr. Boldover (’08, ’14) conducted graduate research in Bernhard Palsson’s laboratory at the University of California, San Diego. Bernhard Palsson is the YC Fan Endowed Professor in the Shu Cheng Gene Lei Department of Bioengineering (Jacobs School of Engineering), an affiliate of Qualcomm Research Institute, and a professor in the Department of Pediatrics. There, Bolver worked to build computational approaches to rapidly develop new experimental and clinical strategies from large biological datasets.
Boldover and Palsson founded Sinopia Biosciences in 2014 to bring that approach to drug development, particularly the issue of avoiding and managing side effects. The company’s strategy was to use tools for “biologically consistent data analysis” and link discoveries to biochemical mechanisms.
They chose to launch their new company at the University of California, San Diego’s Qualcomm Institute (QI) Innovation Space, with Sinopia Biosciences being one of the first tenants. For Bodvar, QI provided more than just office space. It provided a collaborative environment where the Sinopia Biosciences team could easily consult with experts from UC San Diego, including experts in intracellular signaling, computational chemistry, movement disorders, and pharmacokinetics. This location also makes it easier to hire UC San Diego interns.
Funded primarily by a Small Business Innovation Research Grant from the National Institutes of Health and additional support from the Michael J. Fox Foundation, Sinopia advanced the identification of drug development candidates. One was SB-0110.
test candidates
In a new study published in scientific translational medicineBoldover and his collaborators set out to test the effects of SB-0110 in rodent and non-human primate models of Parkinson’s disease.
They had reason to think this compound was worth investigating. Their computational analysis suggested that SB-0110 could suppress the biological changes associated with dyskinesia while preserving gene activity patterns associated with the benefits of L-dopa.
The compound also had practical benefits. It is based on an older heart drug with a history of use outside the United States, so the team had some confidence in its safety. And their target, a brain signaling system called PKA-II, is already linked to exercise and dopamine responses, which is exactly the biology they were hoping to influence.
To conduct this research, Sinopia Biosciences collaborated with both private and academic partners and leveraged the expertise of UC San Diego through Susan Taylor, Professor Emeritus of Pharmacy, Chemistry, and Biochemistry, and J. Andrew McCammon, Professor Emeritus of Pharmacology, as well as Parkinson’s disease modeling experts at Atuka and Motac Neuroscience.
When the results came in, they showed that the compound provided more than a modest improvement. This significantly reduced dyskinesias and improved locomotion to a similar degree as increasing the dose of L-dopa, without worsening normal involuntary movements, in animals where L-dopa alone was insufficiently effective.
Looking to the future
Although preclinical results don’t always translate seamlessly to humans, Bordover said, “We’re very excited that this has a good chance of working clinically.”
For patients and families looking for new options, new treatments are not just around the corner, but they are a step in the right direction. Sinopia has completed the toxicology studies required for regulatory review and hopes to begin first-in-human trials next year.
If all goes well, Boldvar estimates the drug could be available to patients within six to seven years.
sauce:
University of California San Diego
Reference magazines:
Boldover, A. Others. (2026) A small molecule attenuates both Parkinson’s disease and L-dopa-induced dyskinesia in an animal model of Parkinson’s disease. scientific translational medicine. DOI: 10.1126/scitranslmed.aec7409. https://www.science.org/doi/10.1126/scitranslmed.aec7409
