A Phase I Study of Pyrimethamine in Patients With GM2 Gangliosidosis
Status:
Withdrawn
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
Adult Tay-Sachs disease and Sandhoff diseases are caused by deficiency of an enzyme called
β-hexosaminidase A, or Hex A in short. This enzyme is located in a particular cellular
component, called lysosomes, inside the brain cells. The reason that Hex A of patients with
Adult Tay-Sachs disease or Sandhoff disease is deficient is because this enzyme had gone
through mutation, resulting in it not working very well. In healthy people, Hex A efficiently
breaks down GM2-ganglioside, which is a by-product from cells of our body. However, patients
with Adult Tay-Sachs disease or Sandhoff disease cannot efficiently break down
GM2-ganglioside in the body. Therefore, these patients have high levels of this by-product in
the brain cells, which causes the brain to be unable to function normally.
There is a drug called Pyrimethamine. This drug is used by doctors to treat specific types of
infections called malaria and toxoplasmosis. Our laboratory test tube studies have shown that
Pyrimethamine can help the Hex A enzyme to function in a normal manner. If Hex A can function
normally in presence of Pyrimethamine, this drug should be able restore the brain malfunction
of these patients since Hex A can now efficiently break down GM2-ganglioside with
Pyrimethamine treatment.
Although results from laboratory test tube studies are promising and Pyrimethamine should
theoretically restore brain function of these patients, we do not know if Pyrimethamine is
safe or if it would actually work in patients. This study is the first study (a Phase I
study) of testing Pyrimethamine to treat Adult Tay-Sachs and Sandhoff diseases. The objective
of this study is to see if Pyrimethamine is safe in these patients and to see if it can
restore the brain function of these patients.
Phase:
Phase 1
Details
Lead Sponsor:
Exsar Corporation
Collaborators:
New York University School of Medicine NYU Langone Health The Hospital for Sick Children University Hospitals Cleveland Medical Center