AI joins the fight against Tay-Sachs

There may be fresh hope in the long fight against Tay-Sachs.

A major investment in Australian genomics research could speed up the diagnosis of rare genetic disease, including one of the inherited conditions that most affect Ashkenazi Jews.

Global artificial intelligence company Anthropic is behind the development, backing the Garvan Institute of Medical Research with high-capacity access to its AI model Claude.

The investment targets two projects. The first is led by Professor Daniel MacArthur, director of the Centre for Population Genomics. His team will build a Claude-based system to interpret genetic variants. These are the changes in DNA that can cause disease, and interpreting them by hand is painstaking and slow.

“More than half of the families affected by severe genetic conditions still don’t have an answer for what is causing their child’s disease, limiting their ability to access new treatments or clinical trials,” MacArthur said.

He said the system would draft interpretations “in minutes rather than hours”, freeing experts to return diagnoses to families faster.

A second project is led by Professor Joseph Powell. His team will use Claude to make sense of single-cell genomic data, the dataset of which is, his team says, the largest of its kind in the world.

The work helps researchers understand how genetic signals lead to disease in specific cells.

Depending on the condition, only 10 to 30 of every 100 families who have a genome sequenced currently receive a diagnosis.

Garvan’s Chief Scientific Officer, Professor Sarah Kummerfeld, said the team is “increasing that diagnostic yield, so that more families have a diagnosis”, and in some cases a suggested treatment.

Kummerfeld explained that genomics is increasingly able to target medical issues like Tay-Sachs and cystic fibrosis.

“I think probably a good example that I know in the Jewish community people would understand is Tay-Sachs disease, where there’s just a single change in one letter of your genetic code in your genome,” she said.

Children with the condition, she added, “have terrible outcomes”.

Tay-Sachs is an inherited, fatal disorder of the nervous system, caused by mutations in a single gene, HEXA, leaving the body unable to make a working copy of an enzyme called hexosaminidase A. Without it, a fatty substance builds up in nerve cells.

Babies with the most common form appear healthy at birth, then decline from around six months of age. Most die by the age of three or four. There is no cure.

The disease is autosomal recessive, meaning a child must inherit a faulty copy of the gene from both parents to be affected.

Among Ashkenazi Jews, roughly one in 27 to one in 30 people carries the mutation. In the general population the rate is about one in 250 to 300.

Kummerfeld said prevention still requires proper screening. Couples who both carry the mutation can be offered IVF with pre-implantation testing that lets them select an embryo without two faulty copies.

“What’s likely to be possible in the future is to actually make a correction to the gene,” she said.

She pointed to cystic fibrosis, another single-gene condition. Patients can now inhale a vector that repairs the faulty gene in their lungs.

Anthropic has sent engineers to work alongside Garvan’s researchers.

“It’s not just giving us some funding and off we go,” Kummerfeld said. “They’re actually working with us, which is really exciting.”