Scientists have identified a compound that could improve the benefits of levodopa treatment for patients with Parkinson’s disease while delaying or preventing side effects that commonly develop with long-term use. The discovery was made at Sinopia Biosciences, a spinout of the University of California San Diego that analyzes large biological datasets to identify novel therapeutic approaches for preventing and managing side effects of existing drugs.
Preclinical findings published today in Science Translational Medicine suggest the drug candidate could significantly enhance the performance of the most effective and widely used treatment for Parkinson’s. If confirmed in clinical trials, the approach could represent a major advancement in the treatment of this increasingly prevalent neurodegenerative condition.
Levodopa can dramatically improve Parkinson’s symptoms, especially during the early stages of the disease. Over time, however, its effects start wearing off between doses, and within five years of treatment, about 40% of patients develop dyskinesia—a complication involving erratic and involuntary movements. Amantadine is currently the only approved drug to treat dyskinesia induced by levodopa, but its psychiatric and vascular side effects significantly limit its use.
“Virtually every Parkinson’s patient takes levodopa,” said Aarash Bordbar, PhD, chief executive officer, chief scientific officer and co-founder of Sinopia Biosciences. “But patients face two major problems with the drug: the reappearance of Parkinson’s symptoms and dyskinesia. There is no drug that can be added to levodopa to address both simultaneously in a robust manner, and that’s what our drug candidate is doing.”
Bordbar’s team analyzed transcriptomics data to understand how levodopa changes gene expression patterns in the striatum, a brain region involved in movement control. The results were compared with a dataset of gene expression changes induced by existing drugs, allowing the researchers to identify compounds that activated the same transcriptional programs responsible for levodopa’s motor benefits while opposing gene expression programs linked to dyskinesia side effects.
“Maximizing clinical benefits of therapeutics while minimizing adverse effects is a central challenge in drug development,” said Bordbar. “By focusing on the pharmacology of an effective drug rather than disease biology alone, the approach prioritizes pathways with demonstrated clinical relevance, increasing translational potential.”
The team identified a promising candidate in trapidil, a drug that has been used for over 50 years in Japan to treat angina. The drug targets PKA-III, a protein involved in movement and dopamine responses within the brain. The researchers then designed a new compound based on trapidil and tested it in mouse and macaque models of Parkinson’s disease.
Results showed that the drug candidate could offer a dual benefit to Parkinson’s patients, simultaneously improving the motor benefits of levodopa while delaying or preventing treatment-related complications—potentially benefiting both long-term users and patients who are newly starting levodopa therapy.
Based on these findings, Bordbar believes there’s a high chance Sinopia’s drug candidate will succeed in clinical trials. This is further supported by the fact the compound is based on a drug that has been safely used for decades. The company is currently completing the toxicology studies required ahead of the first-in-human clinical trial, which is expected to begin next year.
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