A failed diabetes drug developed in San Diego is being revived as a potential treatment for a fatal, inherited brain disease.
In a study published Monday in Nature Medicine, San Diego researchers working with scientists across the country report promising results against Huntington's disease in mice and human cells.
Senior author Albert La Spada, a professor at UC San Diego, said, "The backstory is, the compound was created by a company for one indication, and then we discovered it could be used for an entirely different indication."
The drug compound, KD3010, was originally developed by a now-defunct San Diego biotech company called Kalypsys. The drug passed initial human safety trials, but stalled under further development.
The drug boosts a protein La Spada and his colleagues found to be deficient in the neurons of Huntington's disease patients.
When administered to mice showing signs of Huntington's, KD3010 lengthened lifespan by 16 percent and improved motor function. The drug also reduced the toxic effects of Huntington's disease in brain cells derived from human patients.
"In fact, of all the treatments that have been tested by my collaborators at Johns Hopkins on neurons from Huntington's disease patients, KD3010 was the most neuro-protective," La Spada said.
Most new drug candidates fail to achieve FDA approval. But La Spada said this study shows some of those failed drugs could be repurposed to fight different conditions.
"It's very important to consider existing compounds that have been shown to be safe in humans and determine if they may have applications that were not envisioned when they were originally produced," La Spada said.
Kevin Lustig co-founded Kalypsys in 2001. As the company's former research director, he worked closely on KD3010. He said it "feels wonderful" to see the drug find new life in the fight against a condition that currently has no treatments.
According to Lustig, Kalypsys ceased work on KD3010 after the FDA pulled Avandia, another diabetes drug that ended up putting patients at greater risk for heart attacks and stroke.
The human safety data on KD3010 were positive, but drug development stalled due to "guilt by association," Lustig said.
"It was really upsetting that it got parked and we couldn't go forward in the diabetes area," said Lustig, now the CEO of San Diego-based Assay Depot (soon rebranding as Scientist.com).
"To have it be potentially useful as a drug candidate against a major disease that affects thousands of people — I couldn't be happier," he said.
KD3010 now faces another uphill climb.
La Spada said proving its effectiveness in actual Huntington's patients will require more human trials. He hopes those trials can be accelerated, since the drug's safety has already been proven.
