Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

This is an interventional treatment trial for Gangliosidoses, GM2 focused on measuring Late-onset GM2-gangliosidosis, pyrimethamine Read More

Inclusion Criteria:

• biochemically and genetically confirmed diagnosis of GM2-gangliosidosis caused by β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes;
• having HEXA or HEXB mutations shown to be responsive to pyrimethamine in vitro;
• over 17 years of age at the time of study initiation;
• able to understand and cooperate with the requirements of the study protocol;
• mentally competent, have the ability to understand and willingness to sign the informed consent form;
• able to travel to one of the three participating study sites;
• women of child-bearing potential must use accepted contraceptive methods and must have a negative serum or urine pregnancy test within one week prior to treatment initiation;
• fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists;
• laboratory values ≤2 weeks prior to randomization must show adequate hematologic, hepatic, renal, and coagulation function; and body weight >40 kg.

Exclusion Criteria:

• serious medical illness, significant cardiac disease or severe debilitating pulmonary disease;
• any hematologic abnormality, especially megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia;
• any active uncontrolled bleeding or any bleeding diathesis (e.g., active peptic ulcer disease);
• possible folate deficiency, and those receiving therapy (such as phenytoin) affecting folate levels;
• any complex disease that may confound treatment assessment;
• pregnant women or women of child-bearing potential not using reliable means of contraception;
• lactating females;
• fertile men unwilling to practice contraceptive methods during the study period;
• unwilling or unable to follow protocol requirements;
• known hypersensitivity reactions, intolerance or adverse reactions to pyrimethamine;
• evidence of active infection, or serious infection within the past month;
• HIV infection;
• a history of cancer of any type;
• receiving any other standard or investigational treatment for any indication within the past 4 weeks prior to initiation of pyrimethamine treatment;
• receiving immunotherapy of any type within the past 4 weeks prior to initiation of pyrimethamine treatment; or any condition or abnormality, which may, in the opinion of the investigator, compromise the safety of patients.