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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Proposed Investigator-Initiated Clinical Trial of Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

Brief Summary: The objectives of this clinical trial are to assess the safety and tolerability, as well as efficacy, of a stepwise dosing regimen of pyrimethamine, starting at 25 mg/day, given as a single dose daily for 4 weeks in patients affected with chronic Tay-Sachs or Sandhoff variants.

Detailed Summary: Patients with late-onset Tay-Sachs or Sandhoff disease will be given increasing doses of Pyr, up to but not exceeding doses used to treat malaria, over a 5-month period. We will follow the effect of the treatment on the levels of Hex A enzyme activity in white blood cells, which are considered to be a reflection of the likely enzyme activity in the brain. We will also follow some other lysosomal enzyme activities to determine if the effect is specific for Hex A. Furthermore, we will examine the effect of the treatment on the levels of GM2-ganglioside in the white blood cells. On the basis of the studies done on cultured skin cells, we expect that treatment with Pyr will increase the levels of Hex A and decrease the accumulation of GM2-ganglioside in the white blood cells.
Sponsor: The Hospital for Sick Children

Current Primary Outcome: Efficacy of pyrimethamine [ Time Frame: Baseline, before exposure to pyrimethamine, and Weeks 4, 8, 12, 16 and 18. ]

Changes in Hex A and Hex B, β-glucuronidase using blood assays


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pyrimethamine Blood levels [ Time Frame: Weekly (1-18 weeks) ]
  • Pyrimethamine efficacy [ Time Frame: 6 months ]
    Measurement of GM2 in blood samples


Original Secondary Outcome: Same as current

Information By: The Hospital for Sick Children

Dates:
Date Received: October 16, 2009
Date Started: August 2009
Date Completion:
Last Updated: February 22, 2012
Last Verified: February 2012