Drug X: An Alternative to Methotrexate in the Treatment of CRIM-Negative Pompe Patients (2012)

Undergraduates: Stuti Das, Suhrad G Banugaria, MBBS

Faculty Advisor: Dr Priya Kishnani
Department: Biology

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Glycogen storage disease (GSD) is a genetic disorder, which results in the defective processing of glycogen synthesis or breakdown in muscle, liver and other cell types. Glycogen Storage Disease Type II (GSD II), also known as Pompe disease, is a deficiency of acid alpha glucosidase. This deficiency results in the accumulation of glycogen in the lysosome, which results in myopathy throughout the body, especially the heart, skeletal muscles, liver, and nervous system. To counteract the deficiency, enzyme replacement therapy (ERT) has been developed to replace the faulty enzyme with Myozyme™ (alglucosidase alfa). However, even within the category of GSD II, a subtype is present: CRIM positive versus CRIM negative, wherein CRIM positive patients have some of the properly functioning enzyme, while CRIM negative patients have at all. Since CRIM negative patients completely lack the ability to make the enzyme, the body will develop antibodies to the therapy thereby leading to complications in the treatment process. Currently, drugs such as methotrexate are used to suppress the immune system while treating the patient with ERT. Our lab is testing an alternative drug (Drug X) to suppress the immune system, to see whether this new drug will allow for treatment to be provided with an eventual rise in antibody titers. We are currently in the process of testing the efficacy of this drug in mice, by monitoring the antibody titers with the injections of both Drug X and Myozyme™.