Scientists use gene-edited sheep to treat deadly childhood brain disease

Scientists in the UK and US have used gene-edited sheep to develop a promising drug treatment for a lethal brain disorder that affects children called infantile Batten disease, according to an article by The Guardian published on Sunday.

A devastating disease

Children affected by Batten disease are burdened by a slew of symptoms including loss of vision, impaired cognition and mobility problems. Making matters even worse, seizures and early death can occur at later stages of the disease.

“The effect on families is devastating,” told The Guardian Professor Jonathan Cooper of Washington University School of Medicine in St Louis, one of the project’s leaders.

The work began as a collaboration with researchers at Collaborations Pharmaceuticals which had found that mice affected by one form of Batten disease known as CLN1 could be cured with a missing enzyme.

“That was encouraging but we needed to test the treatment in larger brains with a structure more like those of a child,” said another project leader, Professor Tom Wishart, of Edinburgh University’s Roslin Institute, where Dolly the Sheep was cloned in 1996. “You cannot extrapolate straight from mouse experiments to humans. Having an intermediate larger model is important.”

The researchers made use of the gene-editing technique known as a Crispr-Cas9 to produce a version of the gene that results in CLN1 in sheep.

“Sheep ovaries were collected from abattoirs, eggs were removed and fertilized. Crispr reagents were added to make the required changes in CLN1 and the eggs were then implanted into surrogate sheep,” explained Wishart.

Now the researchers had a group of sheep carrying the faulty gene.

“These are symptomless carriers, like the parents of Batten disease children,” added Wishart. “From these we could then breed sheep that have two faulty copies. These go on to develop a disease like those children and became the subjects of our therapy trials.”

Batten disease creates havoc in children because they are missing an enzyme made by healthy CLN1 genes. This causes their bodies’ lysosomes, the parts responsible for recycling waste that accumulates in cells, to malfunction.

Moving to human trials

The study on mice found that simply injecting the missing enzyme into the brain of these animals substantially improved their condition. However, it was still not yet safe to move to human trials.

“You can miss two crucial issues,” added Cooper. “How to deliver the drug to the right place in a bigger brain and how to scale up dosing.”

That’s why researchers had to repeat the experiment with sheep. Using these animals, the scientists were able to estimate an appropriate dose and the route to deliver it to the brains of sheep which were bigger than mice brains and closer to humans.

This study reported clear improvements in the sheep suffering from the disease. However, the researchers insist that additional years of research are still needed to optimize the treatment and ensure its safety and viability.

“We have gained enormous insights that will help in the development of therapies for children one day,” said Wishart. His point was backed by Cooper. “We have still some way to go but we have taken a very important step.”

The research is published in the Journal of Clinical Investigation.