Steve Gitelman, MD
Two UCSF studies take a closer look at drugs known as immunomodulators—teplizumab and abatacept—that tweak the immune system that goes hay wire in people with type 1 diabetes, attacking pancreatic beta cells that produce insulin. As a result, those with type 1 diabetes require external insulin, which is administered through injections or an external pump, for their survival.
In research led by Steve Gitelman, MD, director of pediatric research at the UCSF Diabetes Center, both drugs have shown the potential to prolong a “honeymoon” phase after the onset of type 1 diabetes, when the remaining functional beta cells still kick out enough insulin for a benefit before shutting down completely.
With teplizumab, which was developed by UCSF Vice Chancellor Jeffrey Bluestone, PhD, researchers wanted to know if the honeymoon could be extended by giving two courses of medication, one shortly after diagnosis and another one year later.
“This is translational science at its essence,” Gitelman said. “Jeffrey Bluestone developed teplizumab in animal models in the lab, and we translated it into carefully run clinical trials.”
Teplizumab energized research into immunological therapies for type 1 diabetes after a 2002 study in which patients given the drug early in their diagnosis showed no loss of beta cell function for an average of one year after drug administration.
Abatacept, on the other hand, known to effectively modulate the immune system in transplant and rheumatoid arthritis patients, was tested for the first time in a major study with type 1 diabetes patients.
In two-year studies, both drugs delayed the destruction of beta cells by an average of ten months compared to patients not taking them, a similar pattern identified in prior research. But the effect waned over time, even after further therapy boosts.
“The good news is the drugs worked,” Gitelman said. “The challenge is that we’re not sure why the effect isn’t more long-lasting. So we have to go back to the lab to understand why they work after an initial dosing, and try to clarify the difference between responders and non-responders.”
UCSF’s Clinical and Translational Science Institute (CTSI) was a critical partner in both studies, as it is in all trials conducted by the Diabetes Center, Gitelman said. The Clinical Research Services, offered by CTSI, assisted with hospital stays, therapy administration, and specimen transport and processing.
“These studies are very labor intensive. A lot of centers can’t do them at all, because they don’t have a strong clinical research center, with access to patient beds, specialized research nurses, and the necessary research laboratories,” Gitelman said.
Now a series of new trials are being built on these past studies, and attempt to continue to improve on past experiences.
CTSI at UCSF is a member of the national, NIH-funded CTSA network focusing on accelerating research to improve health. The Clinical Research Services are among a wide range of CTSI resources and services that support research at every stage.
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