​Researchers from Duke-NUS and Duke University, US, identified a potential treatment strategy for the management of glycogen storage disease Ia (GSDIa), a hereditary metabolic disorder. 

  • GSDIa is a genetic metabolic disorder that requires lifelong dietary therapy
  • Duke-NUS and Duke University research team found that a transplant drug helps fat metabolism in cell and animal models

Patients with GSDIa, also known as von Gierke disease, have to eat frequently and consume raw cornstarch  on a strict schedule to manage their condition. But eventually, many of them die from liver tumours and renal failures.

“It’s a devastating disease,” said Professor Paul Yen from Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, the main author of the study. “Diet management is currently the only way to manage the disease, but it can’t prevent the more complex symptoms of the disorder related to organ failure.”
The team found that the autophagy process, in which a damaged cell degrades and recycles itself for use by other cells, was impaired in animal liver cells modelled on GSDIa. The impaired autophagy process led to impaired fat metabolism that would eventually cause fatty liver.
The team induced autophagy in cell and animal models by using Rapamycin, a drug commonly prescribed to prevent transplant rejection, and found improvement in liver size and function.
Benjamin Farah, Duke-NUS MD-PhD student and first author of the study, said, “Activators of the autophagy pathway could be useful for treating GSDIa and other metabolic disease with fatty liver, without relying on the missing enzyme [that helps metabolism of fat].”
Said Dr Dwight Koeberl, from Duke University School of Medicine, “At Duke, we’ve been working on gene therapies to target the missing enzyme, but I’m excited about the alternate treatment strategy that these findings offer.
The possibility of using other approved drugs to develop therapeutic strategies to treat GSDIa gives us a more immediate solution. “