View clinical trials related to Sandhoff Disease.
Filter by:The goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders.
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.
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.
We want to see if Zavesca (or miglustat) is safe and can be tolerated by patients with acute infantile onset GM2 gangliosidosis - classical Tay-Sachs and infantile onset Sandhoff disease. We know that miglustat inhibits the formation of GM2 ganglioside, the compound that is stored in the brains of children with Tay-Sachs and Sandhoff disease. Since it inhibits the synthesis of ganglioside, miglustat may be able to reduce or delay the onset of clinical symptoms.
Hypothesis: To characterize and describe disease progression and heterogeneity of the gangliosidosis diseases. This research study seeks to develop a quantitative method to delineate disease progression for the gangliosidosis diseases (Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis) in order to better understand the natural history and heterogeneity of these diseases. Such a quantitative method will also be essential for evaluating any treatments that may become available in the future, such as gene therapy. The data from this study will be necessary to provide end-points for future therapies, guide medical decisions about treatment, provide objective measurement of treatment outcomes, and accurately inform parents regarding potential outcomes.
Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). This protocol also considers other inherited metabolic diseases such as, but not limited to, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome or Sandhoff disease, I-cell disease (mucolipidosis II). For patients with advanced or rapidly progressive disease, the morbidity and mortality with transplantation is unacceptably high. Unfortunately, there are no viable alternative therapeutic options for these patients; if transplantation is not performed the patients are sent home to die. Our group at Minnesota has developed a new protocol incorporating transplantation using a reduced intensity conditioning regimen designed to decrease toxicity associated with the transplant procedure. This regimen will make use of the drug clofarabine, which has lympholytic and immune suppressive properties without the neurologic toxicity observed in the related compound, fludarabine, commonly used for transplantation. In addition, several agents providing anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of the disease processes. This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential neurologic, neuropsychologic, imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include pharmacokinetics of clofarabine and mycophenolate mofetil (MMF). In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.
The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for an inherited metabolic storage disease.