First mRNA Treatment for Glycogen Storage Disease Already in Testing Phase

Disease with an Unfavorable Prognosis

Glycogen storage disease type Ia is caused by a deficiency of the enzyme glucose-6-phosphatase, which converts a key substance in carbohydrate metabolism, glucose-6-phosphate, into glucose, which is released from the liver into the blood when needed. The dominant symptom of the disease includes episodes of hypoglycemia, starting in infancy, which represent a serious and potentially life-threatening complication. These episodes are more frequent during febrile states and may be accompanied by the development of lactic acidosis.

The disease is also associated with other organ damage, such as nephromegaly with impaired renal function and gouty arthritis. The goal of therapy is to prevent episodes of severe hypoglycemia and metabolic acidosis mainly by regular nutrient intake. From toddlerhood, corn starch is also administered to patients after every meal to prevent hypoglycemia. The prognosis in childhood is generally good with proper treatment; however, in adulthood, it is associated with cardiovascular, hepatic, and renal complications.

Progress in Treatment Due to the Pandemic

Until the COVID-19 pandemic, awareness of mRNA treatments among the public was not widespread, despite the fact that this method has been intensively studied since 1960. The pharmaceutical company Moderna, after successfully developing an mRNA vaccine against COVID-19, is now bringing another therapy based on mRNA technology to the clinical testing phase. In this case, it is not a vaccination but a causal treatment.

Under the designation mRNA-3745 lies an intravenous preparation containing mRNA coding for the deficient enzyme glucose-6-phosphatase. Simply put, the goal of the therapy is to teach certain cells to produce the enzyme so that the body can effectively metabolize glycogen and patients do not rely on regular corn starch intake to prevent hypoglycemia.

First Application in Clinical Practice

The new type of mRNA therapy has entered a phase I clinical study, and in June 2022, the therapy was administered to the first-ever patient. The recipient was 20-year-old American Loveah Hernandez from Texas, who first exhibited symptoms of glycogen storage disease at 6 months of age and has since relied on regular corn starch intake.

The goal of the study Ba1ance is to evaluate the clinical efficacy, safety, tolerability, and pharmacological parameters of the therapy. Currently, we must await the initial results of clinical testing, which may determine the future of mRNA therapy (not only) for glycogen storage diseases.

(holi)

Source: Walker J. Breaking barriers – the first patient in the world receives moderna mRNA trial infusion for glycogen storage disease at UConn Health. UConn Today, 2022 Jun 8. Available at: https://today.uconn.edu/2022/06/breaking-barriers-the-first-patient-in-the-world-receives-moderna-mrna-trial-infusion-for-glycogen-storage-disease-at-uconn-health