Tay-Sachs disease has escaped effective treatment since 1883 when an ophthalmologist names Warren Tay found small red spots in the back of the eyes of some infants.

According to an article in Scientific American, in 1887, Bernard Sachs – an American neurologist – wrote a paper on the neurological symptoms of the disease.

Dr. Sachs noticed that certain abnormalities were not evident until the children were two or three months old. Yet some parents noticed that their child was more lethargic than other children at the same age.

Dr. Sachs reported the history of one child who seemed to be listless, unable to change positions, grew weaker, developed bronchial problems, and died of pneumonia in August 1886.

This account of the disease has carried forward every year until 2022, when two infants were treated with gene therapy for Tay-Sachs. The drug has taken fourteen years to be developed.

About Tay Sachs

It is a severe neurological disease caused by an insufficiency of the enzyme HexA. The enzyme breaks down fat-like substances in the brain that normally exist in harmless amounts.

In the absence of HexA, these fat-like substances will accumulate, become toxic, and kill neurons. Left untreated, Tay Sachs patients may die by their fifth birthday. The disease may also strike people at a later age, but their symptoms usually begin in their teens and worsen over decades.

No Available Treatment

Patients who are treated aggressively may achieve extended overall survival but without improved neurological function.

Researchers have found that there is only one way to approach an effective treatment for Tay Sachs, and that is to recreate the HexA enzyme. The problem is that the blood-brain barrier, a filtering system that blocks certain substances, prevents some molecules from entering the brain.

Miguel Sens-Esteves, one member of a research team at UMASS Medical School, wrote an essay for Conversation US explaining a gene therapy they developed that can circumvent the blood-brain barrier.

Their remedy is to use two harmless viruses (viral vectors) which deliver DNA instructions that direct the brain cells to produce the enzyme that is missing. The vectors have had their genes removed, lost their ability to replicate, and are not infectious.

The Production of HexA

Once the DNA instructions enter the cells, they remain there enabling long-term HexA production. The research team tested the delivery system on various species of animals. It appears that if they deliver the treatment to the center of the brain, enzymes can move along its connections and be distributed to other areas in the brain.

The First Gene Therapy Treatment

The first child to receive treatment was 2 ½ years of age and had late-stage symptoms. Within three months after treatment, the child’s muscle and eye control improved.

They are now five years old and in stable health, as well as being seizure-free. This would have been impossible without treatment.

The second child received the treatment at the age of seven months. At a three-month post-treatment review, the doctors saw an improvement in brain development. The child has remained free of seizures after twenty-four months.

A Need for More Testing

The two aforementioned cases represent the first time the treatment was administered to humans. Therefore, the scientists used a low dose which was well below the doses used in their animal studies.

The next step is to arrange follow-up trials that will test the efficacy and safety of increased doses and to do so in larger patient cohorts.

Challenges to Drug Development

Dr. Sens-Esteves explains that manufacturing costs, as well as the cost to test the drugs for rare diseases, leave little chance for profitability.

However, the team was able to make the drug available for treatment with funds from a family whose child participated in the clinical trial. As in this instant, research for these ultra-rare diseases is funded by foundations, parents, and grants from the federal government.

Dr. Sens-Esteves further explained that their program will continue to develop viral vector therapies with help from foundations and families. He said estimates of rare diseases exceed seven thousand different types worldwide.