Leading the worldwide fight to treat and cure
Tay-Sachs, Canavan, GM1 and Sandhoff diseases

Potential Therapies

Overview of Technology Approaches

NTSAD is dedicated to leading the worldwide fight to treat and cure Tay-Sachs, Canavan, GM1, and Sandhoff diseases. Treating these diseases falls into two general categories: restoring the missing enzyme or decreasing the waste accumulation. The scientific community generally agrees that no single therapy will cure these diseases but that rather a combination of approaches will slow, halt and even reverse the damage caused by these diseases. This section provides a basic introduction into these potential therapies.

These diseases are especially difficult to treat because they affect the central nervous system (CNS) which is protected by the blood brain barrier.

NTSAD has developed a comprehensive research strategy taking into consideration a therapeutic approach's potential stop or slow disease progression, reverse damage, and timeline to market. Learn more about the NTSAD Research Initiative.

NTSAD's world class Scientific Advisory Committee closely monitors all areas of potential therapy and new developments that may offer potential cures for our diseases so families can focus on enjoying time with each other.

Natural History Studies

The disease natural history is a comprehensive description of the disease without any interventions. Establishing this history is a vital step toward effective clinical trials because the natural history of the disease provides objective, quantifiable ways to definitively say whether a potential therapy is having the desired affect.

Read more on Natural History Study


Biomarkers are ways to objectively measure disease severity to better understand how a potential therapy may be helping. A biomarker may be a measurable substance such as the substrate accumulated in the disease or it may be imaging that shows disease improvement.

Read more on Biomarkers

Restoring Enzyme Function

The majority of research and potential therapies focus on restoring the enzymes because the missing or deficient enzymes are the primary pathology, or disease causing mechanism, in Tay-Sachs, Sandhoff, GM-1, Canavan and related genetic diseases.  Read more on approaches to restore enzymes:

Gene Therapy
Stem Cell Therapy
Bone Marrow Transplant
Pharmacological or Molecular Chaperone Therapy
Enzyme Replacement Therapy
Stop-Codon Read Through Technology

Decreasing Waste Accumulation

Reducing waste accumulation is another strategy to treat Tay-Sachs, Sandhoff, GM-1, Canavan and related diseases. It does not have the same potential to cure the disease because it does not address the primary disease causing mechanism, the missing or deficient enzyme. However, if successful it could slow or stop the disease progression giving the most precious gift -   time.

Read more on Substrate Reduction Therapy

Canavan - A Closer Look

Canavan is a different type of disease than Tay-Sachs, Sandhoff and GM-1. It is a leukodystrophy. In addition to the approaches listed above another potential therapy is Acetate Supplement Therapy for Canavan. Also scientists are still learning about Canavan pathology or disease causing mechanism. There is ongoing gene therapy research as well. Understanding the disease causing mechanism is vital to development of effective and safe therapies.

Evaluating Experimental Therapies

Resources for those wanting to explore experimental therapies in the U.S. and abroad. Read more on Evaluating Experimental Therapies


Gene Therapy

What is Gene Therapy?

The goal of gene therapy is to restore the missing enzyme by introducing the correct genetic code so proper enzyme production can occur. The correct genetic code may be delivered in various ways but the most common approach uses a viral vector. The non-disease-causing virus is genetically altered to contain the missing genetic code and is used as a vehicle to introduce the correct genetic information and thereby begin proper enzyme production.

What is the Current Status of Gene Therapy?

The Tay-Sachs Gene Therapy (TSGT) Consortium was formed in 2007 with the goal of initiating a gene therapy clinical trial for Tay-Sachs disease and Sandhoff disease. The research is in pre-clinical development stages. Read more about The Tay-Sachs Gene Therapy (TSGT) Consortium Results and Progress toward a Cure.

Since the early 1980s over 20 children have received experimental Canavan gene therapy. Many parents feel that gene therapy helped their child. The results have been published. Available to download here.

A different type of gene therapy for Canavan has recently shown very exciting results in Canavan mice. NTSAD is delighted to partner with the Canavan Research Foundation to fund this project. Visit our Research Initiative page to learn more about this project and other promising efforts funded by NTSAD.

In 2008 the world's first gene therapy for inherited blindness showed sight improvement. The findings are a landmark for gene therapy technology.

What are the Challenges to a Gene Therapy?

Gene therapy has a lot of promise to cure but the Food and Drug Administration (FDA) has not yet approved any gene therapy for market in the United States. The first gene therapy treatment was approved in Europe in November 2012. It is a treatment for patients with a lipoprotein lipase deficiency. Some of the challenges to develop a safe and effective gene therapy include:

  • difficulty of creating effective vectors for gene delivery to the brain
  • need to introduce the gene into a large number of cells to be effective
  • challenge of inserting the genes into the appropriate brain cells
  • potential for an oncogenic (cancer) event to occur as a result of the insertion of the gene into the cell's chromosomes

Learn more:

Stem Cell Therapy

What is Stem Cell Therapy?

Stem cells differ from other kinds of cells in the body. All stem cells - regardless of their source - have three unique properties:

  1. Capable of dividing and renewing themselves for long periods of time
  2. Unspecialized
  3. Can give rise to specialized cells

These unique properties could be used for cell-based therapies in which stem cells that are genetically altered to produce the missing enzyme are delivered to the brain or central nervous system.  

What is the Current Status of 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 Research Initiative.

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

What are the Challenges to Stem Cell Therapy?

Stem cell therapy has a lot of promise to cure but faces formidable challenges to develop safe and effective therapies. Some of the challenges include:

  • Risk of an immune response leading to rejection of these cells
  • Risk of cells differentiating in an unexpected way
  • Transmission of donor-related diseases that reside in those stem cells
  • Ability to scale-up the amount of cells needed for humans
  • Acceptance of this approach owing to the controversy over embryonic stem cells

The embryonic stem cell controversy is becoming less of an issue as scientists have recently discovered how to manipulate adult cells into a stem cell state but more work is necessary to understand their therapeutic properties and potential.

Also see Bone Marrow Transplant

Learn more:

Pharmacological or Molecular Chaperone Therapy

What is Pharmacological or Molecular Chaperone Therapy?

Pharmacological or Molecular Chaperones are small molecules that are able to cross the blood brain barrier into the central nervous system. These chaperones attach to an inactive enzyme so that it takes the correct functional shape. Chaperones only work with certain mutations.

What is the Current Status of Pharmacological or Molecular Chaperone Therapy?

Pyrimethamine was investigated as a potential therapy for Late Onset Tay-Sachs. This study was especially challenging both because of lack of biomarkers and because it was believed that at the wrong dose the drug might actually reduce enzyme function. They concluded that pyrimethamine treatment enhances enzyme activity in LOTS at certain doses. However, significant side effects were experienced by a number of patients. Read more here.

Other chaperones are being investigated in Fabry and Pompe, which are lysosomal storage diseases.

What are the Challenges of Pharmacological or Molecular Chaperone Therapy?

Chaperones have the potential to reduce enzyme function if given at the wrong dose. Chaperones only respond to certain mutations. For example, pyrimethamine only responds to certain mutations causing Late Onset and Juvenile Tay-Sachs.

Learn more:

Substrate Reduction

What is Substrate Reduction?

Substrate reduction therapy uses small molecules that pass the blood brain barrier into the central nervous system and decrease the amount of substrate or waste product that accumulates. Think of a clogged sink with the faucet running and turning down the faucet. The water will still fill up the sink but it will take longer.

A visual representation:

a) In most individuals the substrate (water) can be degraded efficiently by adequate enzyme volume (hole in sink).

b) In affected individuals the amount of enzyme is insufficient to efficiently degrade the substrate and it accumulates.

c) In affected individuals treated with substrate synthesis reduction therapy, the amount of substrate is decreased to match the amount of residual enzyme to prevent accumulation.



What is the Current Status of Substrate Reduction Research?

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.

Zavesca® (miglustat)
Clinical trials in babies, children and adults with Tay-Sachs and Sandhoff of the substrate inhibitor Zavesca® (miglustat) did not show therapeutic benefit. Zavesca is FDA approved for Gaucher which provides families affected by other lysosomal diseases the option of using the drug for off-label use. The FDA did not approve Zavesca®  for Niemann-Pick Type C (NPC) but this use was approved in Europe and Canada.

Zavesca may have a small therapeutic effect on children affected by Juvenile GM-1. Contact our Executive Director at This email address is being protected from spambots. You need JavaScript enabled to view it. or (800) 906-8723 to learn more.

What are the Challenges of Substrate Reduction?

The primary challenge of substrate reduction is keeping up with the rapid accumulation of waste production. Zavesca can have significant gastrointestinal side effects such as diarrhea which was extremely debilitating to many participants in the Late Onset Tay-Sachs clinical trial.

Learn more:

Download the Subcommittee on Experimental Therapies paper on substrate reduction therapy here