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Tay-Sachs, Canavan, GM1 and Sandhoff diseases

Tay Sachs Research

Tay Sachs Research Overview

Tay Sachs is a lysosomal storage disorder. It is caused by a mutation in the gene responsible for the vital enzymes called beta hexaminidase A (Hex-A). The role of Hex-A is to degrade a fatty substance or lipid called GM-2 ganglioside. In the absence of the enzymes, GM-2 accumulates abnormally in cells, especially in the nerve cells, or neurons, of the brain. This ongoing accumulation, or "storage", of GM-2 causes progressive damage and eventually death of the cells.

For more information, see All About Lysosomal Storage Disorders

Tay Sachs research is usually performed simultaneously with Sandhoff disease research. This is because these two diseases have a similar underlying biochemical mechanism.

For information on participating in a study, please visit Studies Recruiting Patients.


Where are we with Tay Sachs Research?

Tay Sachs Gene Therapy Consortium

The Tay-Sachs Gene Therapy (TSGT) Consortium seeks rapid development of the most effective gene therapy approach for the clinical trial. To accomplish this goal, scientists and clinicians are pooling their resources and extensive experience in experimental gene therapy to devise the most effective adeno-associated virus (AAV)-based gene therapy approach for treating Tay-Sachs and Sandhoff disease.

Animal models have been created and vectors have been manufactured and tested. Learn more about Tay-Sachs Gene Therapy Consortium

Gene therapy Investigation in felines

Intravascular gene therapy for feline GM2 gangliosidosis (2015 Grant)

Aims to optimize IV gene therapy to treat the manifestations of Sandhoff Disease in both the central nervous system, and the rest of the body. This research will also benefit Tay Sachs Disease. Learn more at 2015 Research Initiative Grants.

Gene Therapy Investigation- late onset Tay Sachs

Generation of a knock in mutant HexB mouse model (2015 Grant)

Aims to create a mouse model which contains a specific mutation in the HexB gene. This mutation leads to a reduced amount of enzyme, as seen in late onset Tay Sachs or Sandhoff Disease. When this is accomplished, this mouse model will then be able to be used in later studies for studying the efficacy of chaperones which are being developed for LOTS/LOSD. Learn more at 2015 Research Initiative Grants.

Substrate Reduction Therapy

Several substrate reduction therapies have delayed symptoms and prolonged survival in Tay-Sachs and Sandhoff mouse models but this success has not always successfully translated into the same results with humans. 

Substrate Reduction Therapy: Zavesca® (miglustat) 

A clinical trial to evaluate the safety and efficacy of SRT using a drug called migulstat (brand name Zavesca) has also been conducted for late onset Tay-Sachs. Miglustat did not result in any measurable clinical benefit in the 20 late onset patients given 200 mg orally three times a day when compared to patients that did not take miglustat. Prominent side effects of the drug were weight loss and diarrhea, as this drug also effects the ability to digest complex carbohydrates. It remains unclear whether earlier treatment in more mildly affected patients would result in benefit. There are reports of benefits to individual patients with Tay-Sachs disease treated with miglustat, and further studies are warranted if coupled with detailed natural history studies to allow better interpretation of the outcomes of the trial.

The NTSAD Scientific Advisory Committee (SAC) subcommittee on experimental therapies recently reviewed the data regarding miglustat’s safety and potential efficacy. View report on Substrate Reduction Therapy.

Off Label use study for Migulstat- currently recruiting participants

Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G) at University of Minnesota - Clinical trial #NCT02030015

This study has IRB approval, but it is not technically a clinical trial so does not have FDA approval.

The investigators are investigating a combination therapy using miglustat and the ketogenic diet for infantile and juvenile patients with gangliosidoses. Miglustat is a drug which was originally approved to help treat mild to moderate type 1 Gaucher disease (another lysosomal storage disorder.) Miglustat is an example of substrate reduction therapy, as described above. A ketogenic diet is a “high-fat, adequate-protein, low-carbohydrate diet.” One study found that this method improved the outcome for one patient with Sandhoff Disease. Researchers are now hoping to investigate this therapy in patients with Sandhoff, Tay Sachs and GM-1.

To learn more, including how to be part of this study please visit Studies Recruiting Patients.

Also see the case study in the European Journal of Medical Genetics

Newborn Screening Investigation

Development and Validation of an MS-MS Method for the Detection of Hexosaminidase Deficiency in Tay Sachs (2015 Grant)

When therapy becomes available for Tay Sachs Disease, discovering the disease as early as possible will be essential. Newborn Screening is performed on a dried blood spot via a technique called “tandem mass spectrometry,” which is used to detect reduced enzyme levels in these blood spots. There have been previous studies where the detection of reduced hexosaminidase activity was developed for Sandhoff Disease. This study aims to determine reference and cut off ranges for Tay Sachs Disease and will then pilot the test in Quebec.

To learn more visit 2015 Research Initiative Grants

Molecular Chaperone Therapy- Late onset Tay Sachs

A 2009 Research Initiative grant from NTSAD was administered to Dr. Joe Clarke to support an open-label Phase I/II clinical trial of pyrimethamine, a pharmacological chaperone, for the treatment of patients affected with late onset Tay-Sachs or Sandhoff disease. This clinical trial evaluated the tolerability of pyrimethamine by patients, as well as the effectiveness of the molecule in raising Hex A levels in blood in a small number of patients. The study found that Hex A level was increased up to 4-fold in people taking 50 mg or less of the medication each day. When the dose was increased to 75 mg per day or higher, most participants had significant side effects, including worsening problems with coordination.

Read the full publication: An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay–Sachs or Sandhoff variants)

A pilot study (conducted prior to the above research) found that, although Hex A levels rose in patients, there was significant beneficial neurological or psychiatric effects.

Read the full research report as published in the Orphanet Journal of Rare Diseases, Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study

Bone Marrow Transplant

Currently there are two centers in the United States that will consider Tay-Sachs, Sandhoff and GM-1 patients for Bone Marrow Transplant - Duke University Medical Center and University of Minnesota. The Duke program is not an approved clinical trial (contact June Allison-Thacker at This email address is being protected from spambots. You need JavaScript enabled to view it. to learn more). Read more about the University of Minnesota study at ClinicalTrials.gov.

Stem Cell Therapy

Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials for spinal cord injuries and diseases related to the eye (from http://stemcells.nih.gov/info/health.asp). Breakthrough work has been done in the Sandhoff mouse model and was partially funded by the NTSAD 2010 Research Initiative Grants, Lee and Snyder.

To learn more, read the research publication Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease, published by Nature Medicine, 2007.

Psychotropic Medications- Late Onset Tay Sachs

A study was done in 2006 where the researchers analyzed patients with LOTS who had taken certain psychotropic medications. They found that these medications worsened the neurological effects of LOTS. Read the full research publication Late-onset Tay–Sachs disease: Adverse effects of medications and implications for treatment.