Sinopia Biosciences' SB-0110 Shows Preclinical Promise in Boosting L-Dopa Efficacy While Reducing Dyskinesia in Parkinson's Disease
核心洞察
Sinopia Biosciences (搜索)' drug candidate SB-0110 boosted L-dopa's therapeutic benefits while simultaneously reducing dyskinesia (搜索) in rodent and non-human primate models of Parkinson's disease (搜索).
The findings, published in *Science Translational Medicine*, address two major unmet needs: the return of Parkinson's symptoms between L-dopa doses and the involuntary movements that affect approximately 90% of patients after nine years of treatment.
SB-0110 targets the PKA-II (搜索) brain signaling system and is derived from an older heart drug with an established safety history outside the United States.
For the more than 8.5 million people worldwide living with Parkinson's disease (搜索), levodopa (L-dopa) remains the cornerstone of treatment — yet its long-term use is plagued by diminishing reliability and the emergence of dyskinesia (搜索), a debilitating side effect characterized by erratic, involuntary movements. Now, a preclinical study led by Sinopia Biosciences (搜索), a startup spun out of the University of California San Diego, offers a potential path forward: a drug candidate called SB-0110 that appears to enhance L-dopa's benefits while simultaneously suppressing its most troubling side effect.
The research, published in Science Translational Medicine on July 15, demonstrated that SB-0110 significantly reduced dyskinesia (搜索) in animal models of Parkinson's disease (搜索). In animals that were not receiving full benefit from L-dopa alone, the compound improved movement to a degree comparable to increasing the L-dopa dose — but without the usual worsening of involuntary movements.
"Virtually every Parkinson's patient takes levodopa," said Aarash Bordbar, chief executive officer, chief scientific officer and co-founder of Sinopia Biosciences (搜索) and a UC San Diego alumnus. "But patients face two major problems with the drug: the reappearance of Parkinson's symptoms and dyskinesia (搜索). There is no drug that can be added to L-dopa to address both simultaneously in a robust manner, and that's what our drug candidate is doing."
A Growing Unmet Need
The World Health Organization estimates that Parkinson's disease (搜索) prevalence has doubled globally over the past 25 years, with more than 8.5 million people affected as of 2019. For patients on long-term levodopa therapy, the challenges are stark: after nine or more years of treatment, approximately 70% develop motor fluctuations — periods when symptoms return between doses — and about 90% develop dyskinesia (搜索). No currently available adjunct therapy addresses both problems simultaneously.
Computational Origins of SB-0110
Bordbar conducted his graduate studies in the UC San Diego laboratory of Bernhard Palsson, the Y.C. Fung Endowed Professor of Bioengineering, where he developed computational approaches to rapidly derive experimental and clinical strategies from large biological datasets. In 2014, Bordbar and Palsson co-founded Sinopia Biosciences (搜索) to apply this methodology — which the company describes as "biologically coherent data analysis" — to drug development, with a particular focus on avoiding and managing side effects.
The company's computational analysis suggested that SB-0110 could preserve the gene-activity patterns associated with L-dopa's therapeutic benefits while counteracting the biological changes linked to dyskinesia (搜索). The compound targets PKA-II (搜索), a brain signaling system already implicated in movement regulation and dopamine responses.
SB-0110 also carries a practical advantage: it is based on an older heart drug with a history of clinical use outside the United States, providing the research team with some confidence regarding its safety profile.
Preclinical Study Design and Results
The study tested SB-0110 in both rodent and non-human primate models of Parkinson's disease (搜索). Sinopia Biosciences (搜索) collaborated with academic and private partners, including Distinguished Professor of Pharmacology, Chemistry and Biochemistry Susan Taylor and Distinguished Professor of Pharmacology Emeritus J. Andrew McCammon at UC San Diego, as well as Parkinson's disease model specialists at Atuka and Motac Neuroscience. Additional collaborators included researchers from the University of Bordeaux, CNRS, and the University of Kassel.
The results showed that SB-0110 produced more than a modest improvement. The compound significantly reduced dyskinesia (搜索) and, in animals with suboptimal responses to L-dopa alone, improved motor function to a level comparable to a higher L-dopa dose — crucially, without exacerbating involuntary movements.
Path Toward Clinical Development
Sinopia Biosciences (搜索), funded primarily by Small Business Innovation Research grants from the National Institutes of Health with additional support from the Michael J. Fox Foundation, is now completing the toxicology studies required for regulatory review. The company, housed at the UC San Diego Qualcomm Institute Innovation Space, expects to begin first-in-human testing next year.
"While pre-clinical results don't always translate seamlessly to humans," Bordbar noted, "we're really excited that there's a high chance that this could work clinically." If development proceeds as planned, Bordbar estimates the drug could be available to patients in six to seven years.