PMM2-CDG is caused by a deficiency of the enzyme phosphomannomutase 2 (PMM2), which converts mannose-6-phosphate to mannose-1-phosphate. Mannose-1-phosphate is an essential sugar molecule in the N-glycosylation pathway and is crucially important for proper protein structure and function. GLM101 is a mannose-1-phosphate replacement therapy that is designed to supply the missing mannose-1-phosphate into cells. Once inside, it can then be incorporated into the N-glycosylation pathway to restore disrupted protein function. Treatment with GLM101 is intended to bypass the genetic block in the pathway, regardless of mutation type, and provide continuous exposure over long periods of time.

Since glycosylation is such an important and ubiquitous process essential to protein function, the body’s failure to correctly produce glycans causes a wide array of symptoms. Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Although the symptoms can vary, many infant patients will display hypotonia (muscle weakness), feeding problems, and failure to thrive. Since almost any organ system can be affected, multiple other symptoms may emerge including liver disease, cardiomyopathy, coagulopathies, stroke-like episodes, and developmental delays. 

To learn more about how PMM2-CDG affects patients, Glycomine has initiated a natural history study, which is the largest longitudinal study ever undertaken for this disease. Initial data have uncovered that secondary adrenal insufficiency is a significant risk factor for this disease that is often masked by other comorbidities. Based on this finding, it is recommended that morning cortisol and ACTH levels should be evaluated at least annually for all patients with PMM2-CDG.

Learn more about the initial data from the natural history study here. For more information about this ongoing study (GLY-000) please visit clinicaltrials.gov and search for NCT03173300.