Science & Technology, Canada (Commonwealth Union) – Type 2 diabetes generally occurs when the pancreas does not make sufficient levels of insulin. Some of the common symptoms include Increased thirst, Frequent urination, feeling hungrier, weight loss without trying, Fatigue, Blurred vision and Slow-healing sores.
Type 2 diabetes is usually managed with medications such as insulin, as well as body weight management, maintenance of a healthy diet and the monitoring of blood sugar levels.
A recent study has demonstrated how the antipsychotic drugs target an enzyme needed for reducing blood sugar.
Scientists have discovered that a class of older antipsychotic drugs may have potential for treating persons with Type 2 diabetes, helping fill a gap among patients unable to take other presently available treatments.
John Ussher, a professor from the Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta and lead author of the study that appeared in the journal Diabetes indicated that there is an increased requirement to seek new therapies for Type 2 diabetes.
As he explained, the drug metformin is one of the most widely used therapeutics for Type 2 diabetes, but approximately 15% of patients are unable to take it. Another widely used drug class such as insulin secretagogues used to treat diabetes is not as effective for later-stage patients, who also require different options.
“For the patients who can’t take metformin, patients with late-stage diabetes where their beta cells aren’t working as well, when you’re trying to find new therapies or new combination therapies as the disease progresses, it becomes more important to find new drug classes that target new mechanisms so then you have more options to try and lower blood sugar in those individuals,” said Professor Ussher.
The mechanism Professor Ussher and the research team focused on succinyl CoA:3-ketoacid CoA transferase (SCOT), an enzyme playing a role in the body’s process of forming energy from ketones. Computer modelling was applied to seek drugs that may potentially interact with SCOT and used by an older generation of antipsychotic drugs, a drug class known as diphenylbutylpiperidines, (DPBP).
Professor Ussher and the team had on prior occasions noted that a specific drug within this class known as pimozide may be repurposed to assist diabetes treatment, but they have since then gone further on their attention to see if more of the DPBP class may also be applied for the treatment of the disease.
Repurposing of the drug is effective as it capitalizes on a main feature of most drugs, that they are not limited to a single target within the body. As Professor Ussher indicated, most drugs actually have a number of targets that can be influenced.
“That’s where repurposing comes in,” says Professor Ussher. “Can we identify the other targets that a drug may interact with, and by identifying those other targets, can this drug serve a purpose for a different disease?”
This is what the lab of Professor Ussher carried out in recognizing the DPBP drug class may target SCOT activity and the dopamine receptors it targets which was its original purpose in treating psychosis.
The information available on the original targets can also give valuable insights while refining and enhancing the repurposed drug. As DPBP drugs were initially antipsychotics, most of their potential side-effects such as drowsiness, dizziness or fatigue arise from their effects on their intended target which was the dopamine receptors in the brain. Professor Ussher’s lab plans to attempt the production of a modified version of the drug class that will not move into the brain and will have lesser possible adverse effects.
Since many previously used medications have been considered in clinical trials in repurposing them to treat new diseases with new targets as they can be used by patients with less time in clinical trials as they have already been established for safety.
