NIH scientists set foundations for potential gene therapy for late Tay-Sachs

Friday August 15, 2025

The study of human cells and mice may have implications for other lysosomal storage disorders

Scientists from the National Institutes of Health (NIH) have managed to reduce the severity of Tay-Sachs (lots) diseases in human cell cultures and a mouse model using a new genetic editing treatment. Lots are a rare form of Tay-Sachs disease, with signs and symptoms such as muscle weakness, loss of coordination, muscle spasms and sometimes the loss of mental function starting at the end of childhood to adulthood. Similar disorders for which this breakthrough has implications include GM1 gangliosidosis, Sandhoff’s disease, Niemann-Pick’s disease, Krabbe’s disease and left-handed disease.

Many is a genetic disorder caused by a mutation in the HEXA Gene which causes an enzyme deficiency which is essential to decompose a fatty substance in the brain, known as Ganglioside GM2. The accumulation of this fatty substance damages the nerve cells in the brain and the spinal cord. The amount of enzyme still produced by the body affects the severity of the disease and the age of appearance. By deploying the correction to the HEXA Gene, scientists were able to increase the activity of the enzyme, known as beta-hexosaminidase A, to delay the appearance of symptoms and considerably prolong the lifespan in the mouse model.

“With a lot, a slight correction will go very far. This assembly may only need to increase enzymatic activity by around 10% for prevent symptoms from worsening and improving their quality of life“Said the author of the newspaper, Dr. Richard Provia, of the National Institute of Diabetes and Digestive and Renal Diseases.” We have understood that the opening of the door to increased enzymatic activity is possible, we must now understand how to do it with a person. »»

Scientists think that this level of preclinical work has laid the foundations on which to build towards tests in human participants. Researchers estimate that prizes affect around 500 people worldwide and currently have around 25 participants in a current study at the Nih Clinical Center in Bethesda, Maryland. The human cells used in this study were given by one of the participants who are unique because they have two copies of the mutated gene.

“I have never met a participant in the study who was so impatient and enthusiastic to be part of the scientific process,” said the study author, Dr. Cynthia Tifft of the National Human Genome Research Institute of NIH. “It is inspiring to work with someone who remains positive and engaged while this disorder deprives them of control over their bodies. I am motivated every day knowing that the work we do is important. ”

Although the current breakthrough is not yet a viable treatment or treatment, researchers think they are on the path of potential treatment. Future studies will study the best ways to provide genetic editing to the central nervous system and the brain. Many other genetic publishing studies have used a method known as adeno-associated virus (AAV) to provide DNA modifications to targeted cells. An AAV is an unwarfted virus that can be designed as a delivery vehicle but faces problems in many adults who may have already developed antibodies against some of the particles of current virus virus used for the administration mechanism. Another obstacle is to design a delivery method that can cross the blood-brain barrier, an area where AAV vectors may need improvement.

Researchers have specifically targeted prizes for this research because other forms of Tay-Sachs disease occur more suddenly. The infantile form of the disorder is generally diagnosed in the first 3 to 6 months of life and is fatal at the age of 4 to 5 years. People with many have about 4 to 6% beta-hexosaminidase at level of enzymatic activity, while infants have no activity in the enzyme, thus making the accumulation of ganglioside GM2 damaging. Children diagnosed with the juvenile form of the disease often die in adolescence.

The mutations of the Hexa gene that cause Tay-Sachs disease are known to be found more often in certain populations, including Jewish communities from Eastern and Central Europe (Ashkénazes Jews), certain French Canadian communities in Quebec, the Cajun community of Louisiana and the old Amish community of the Order in Pennsylvania. In the United States, pregnant women and their partners often receive a blood test to identify carriers of the change of Hexa gene which causes Tay-Sachs disease.

The NIDDK, which is part of the NIH, leads and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The research interests of the Institute include diabetes and other endocrine and metabolic diseases; digestive, nutrition and obesity diseases; and renal, urological and hematological diseases. For more information, visit https://www.niddk.nih.gov/.

On the National Institutes of Health (NIH): The NIH, the country’s medical research agency, includes 27 institutes and centers and is a component of the American department of health and social services. NIH is the main federal agency that leads and supports basic, clinical and translational medical research, and studies the causes, treatments and remedies for common and rare diseases. For more information on the NIH and its programs, visit www.nih.gov.

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Reference

Allende, M et al. “The basic edition targeted by the SNC of the major late Tay-Sachs mutation attenuates the disease in mice.” The Journal of Clinical Investigation. J Clin Invest. https://doi.org/10.1172/jci183434.