Tay-Sachs Disease Research

As there is currently no successful treatment for individuals with Tay-Sachs disease, there is a need for significant research into therapeutic techniques that could be useful in the treatment for the disease.

Among the most promising research at this point in time are enzyme replacement therapy (ERT), the Jacob sheep model, substrate reduction therapy, and increasing the activity of β-hexosaminidase A.

What is Tay-Sachs Disease? (GM2 Gangliosidosis)


ERT has been considered as an approach for the treatment of Tay-Sachs disease and other lysosomal storage disorders.

The aim of ERT is to provide a replacement of the HEXA enzyme that can play the role of the non-functional enzyme of individuals with the disease. However, this process is limited by the physical size of the enzyme, which appears to be too large to traverse the blood-brain barrier (BBB) as necessary.

Some research has investigated the possibility of administering the HEXA enzyme directly into the cerebrospinal fluid (CSF) to surpass this issue. However, current research has not been able to show the successful uptake of the enzyme, even when it is administered directly to the central nervous system (CNS).

To date, this research approach has been futile; however, current researchers continue to examine the mechanism and consider administration techniques of the enzyme that could be effective.

Jacob Sheep Model

A rare breed of sheep, known as Jacob sheep, has been used as a model in the research of Tay-Sachs disease due to their susceptibility to the disease. The pathophysiology and the specific gene mutation of the disease are virtually identical in humans and these sheep, which advocates for the use of these animals as a research model.

Of particular note, research has discovered a certain mutation in the HEXA complimentary deoxyribonucleic acid (cDNA) of sheep with Tay-Sachs disease, known as G444R, which is a missense mutation. This arises due to a change of nucleotide at exon 11, leading to the splicing of the exon before it can be transcribed.

Although this finding has yet to provide a treatment for Tay-Sachs disease, it is a promising lead that is being investigated further in gene therapy clinical trials that may expand future treatment options.

Substrate reduction therapy

Substrate reduction therapy is a technique that involves the use of enzymes to increase the catabolism of the GM2 gangliosides in the CNS and thus substitute the role of the missing HEXA enzyme. The aim of this treatment approach is to prevent the accumulation of lipids, as well as the development of symptoms and progression of the disease.

Sialidase is one enzyme that has been considered in this therapeutic approach, as it enables the bypass of the genetic defect and the healthy metabolism of GM2 gangliosides to occur. Although this could be a promising treatment for Tay-Sachs disease, it has yet to be developed into a pharmacological form that is safe and effective.

Miglustat is also being investigated as a possible treatment, which works with an antagonistic effect on the glucosylceramide synthase enzyme. This enzyme is important in the synthesis of GM2 gangliosides and could, therefore, help in the treatment of the disease.

β-hexosaminidase A activity

Another approach that has been studied for the treatment of Tay-Sachs disease has been to increase the activity of the HEXA enzyme so that the deficiency that characterizes this disease is less significant.

This is primarily considered an option for late onset Tay-Sachs disease; however, patients with infantile Tay-Sachs disease tend to lack the enzyme completely and would not benefit from an increase in the spectrum of activity.

Pyrimethamine is a drug that has shown some activity in this area. Unfortuantely, the overall efficacy of this drug is not high, as the activity of β-hexosaminidase A is still much lower than in unaffected populations.


Further Reading

Last Updated: May 17, 2021

Yolanda Smith

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Yolanda Smith

Yolanda graduated with a Bachelor of Pharmacy at the University of South Australia and has experience working in both Australia and Italy. She is passionate about how medicine, diet and lifestyle affect our health and enjoys helping people understand this. In her spare time she loves to explore the world and learn about new cultures and languages.


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  1. Cindy Rumlow Cindy Rumlow United States says:

    re:  Tay-Sachs, specifically, Late or Adult Onset

    My oldset son, not pictured, is 25.  At 19 he was diagnosed as being afflicted with schizophrenia.  It was after doing ancestral research for my paternal grandmother that I learned she was of Jewish (probably ashkennazi) heriztage) and I know I have 3 cousins who died from infantile Tay Sachs.  My son's condition is severe and he is essentially lost to us; I still would like to know if I can learn if he is possibly afflicted with LOTS or if there is a way to test for this through me? thank you for your help, Cindy Rumlow

  2. S Clark S Clark United States says:

    My grandma had Schizophrenia... is it related to tay-sachs? I just did a dna test because i am trying to find out dna paternal relatives when I tested as a carrier for tay-sachs. Wow this just explains so much and I am a bit stunned and floored. She would suffer from delusions etc and paranoid behavior. But my question was this. I was placed on some blood pressure meds and it was causing me to get 10-15 cramps a day extremely painful. I called my doctor and she said it could not be the blood pressure diuretics. If it possible as a carrier to have lower enzymes that can flush out with diuretics causing the side effects of cramping? As I had seen cramping is symptoms... but other wise just normal cramping. The other thing is getting this news this week I have decided to test my kids one of them grown to see if they are carriers. But I really have a strong question on how the enzyme flushes out or not? hmmm  any thoughts?

  3. Tayton Cullen Tayton Cullen United States says:

    Would it be possible to cure Tay-Sachs Disease by putting a Hex A enzyme into the fetus while it is developing or would this cause negative effects on the developing fetus? I would like to know for a project I am doing about this disease.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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