Metformin could treat rare metabolic disorder experienced by infants

Metformin could treat rare metabolic disorder experienced by infants

The diabetes drug metformin could be used to treat a rare inherited metabolic disorder called Maple Syrup Urine Disease (MSUD), a new study reports.

Researchers at the Buck Institute for Research on Aging found metformin, a commonly used type 2 diabetes drug, could be a novel treatment for MSUD, and hope their findings lead to clinical trials in the near future.

MUSD, a pediatric disorder, is characterised by sweet-smelling urine with an odour similar to that of maple syrup. It is identified in one in 180,000 births. Patients who are diagnosed early have to eat a formula-based diet, but can go on to live normal lives. However, if MSUD is left untreated then infants can die due to a toxic build-up of keto-acids within weeks of birth.

The only proven treatment for the condition is a liver transplant, but Buck Institute researchers used metformin to reduce the toxic acid levels associated with MSUD.

In skin cells derived by MSUD patients, metformin lowered levels of toxic ketoisocaproic acid (KIC) by 20 to 50 per cent. Metformin also reduced KIC levels by 69 per cent in the skeletal muscle of mice bred to have MSUD.

Senior author Arvind Ramanathan, PhD, said: “We think there is a clear path to a clinical trial and we are hoping that physicians who treat MSUD patients will start pushing in that direction. There is a definite need for novel interventions.”

Ramanathan was originally investigating how certain enzymes affect aging before he made this discovery. In studying the enzyme BCKDH, which is defective in MUSD and has decreased activity with normal aging, Ramanathan observed that the enzyme is implicated in obesity and diabetes.

He believes this enzyme could be involved in several other age-related conditions. “This is a prime example how aging research can have a significant impact on people at any age and the work also highlights the value of studying drugs already approved by the FDA,” he added.

Ramanathan concluded: “We plan on building on these insights to further our research aimed at extending the healthy years of life for all of us.”

The findings appear in the journal Scientific Reports.