Researchers investigating new ways to improve glycemic control in type 2 diabetes have found that an older class of antipsychotic drugs may lead to a new class of treatment for hyperglycemia. Researchers have proposed that the old drug could be repurposed directly to treat diabetes, but it could also be modified slightly to target blood sugar control more specifically.
A few years ago, a team of researchers at the University of Alberta discovered a potential new therapeutic target for type 2 diabetes. Animal studies have shown that elevated levels of an enzyme called succinyl CoA:3-keto acid CoA transferase (SCOT) are associated with hyperglycemia. Also, decreased SCOT levels in obese mice significantly improved glycemic signs.
So instead of trying to develop an entirely new molecule that inhibits SCOT, researchers turned to computer modeling to see if there were any existing drugs that could interact with the SCOT enzyme. According to John Ussher, lead author of the new study, this kind of drug repurposing would accelerate the process of clinical development and allow for a rapid jump to early-stage human clinical trials.
“It speeds up the process somewhat because we already have safety data,” Ussher explains. “Also, from an economic standpoint, many of these drugs being sought for reuse are old, out of patent, and cheap.”
In 2020, Ussher and colleagues were the first to find that an old antipsychotic drug called pimozide successfully inhibited SCOT activity in obese mice. The drug has also successfully ameliorated hyperglycemia due to obesity in animals.
Now, in a new study, researchers have demonstrated that several other drugs in the same class of antipsychotics appear to function effectively as SCOT inhibitors. This class of drugs was developed in the 1960s and is still in use today.
“We’ve tested three drugs so far, and they all interact with this enzyme,” Ussher said. “They all improve glycemic control by preventing muscles from burning ketones as a fuel source. I believe that is the reason why
Since the DPBP drug is already an approved drug, the researchers hope to move quickly into pivotal human trials. be established.
Following that, some modifications may be required to function as a more targeted drug for type 2 diabetes. There is a nature. The ideal outcome of this study would be to design the drug so that it cannot enter the brain and focus only on her SCOT inhibition in other parts of the body.
“What’s exciting for us is that a whole family of these compounds appears to be interacting with this protein. [SCOT] It can improve glycemic control in type 2 diabetes,” adds Ussher.
A new study was published in a journal Diabetes.
Source: University of Alberta
