“The effect on families is devastating,” said The Guardian Professor Jonathan Cooper of Washington University School of Medicine in St Louis, one of the project’s leaders.
The work began with a collaboration with researchers from Collaborations Pharmaceuticals who discovered that mice affected by a form of Batten disease known as CLN1 could be cured with a missing enzyme.
“It was encouraging, but we needed to test the treatment in larger brains with a structure more like a child’s,” said another project leader, Professor Tom Wishart, from the Roslin Institute in the United States. University of Edinburgh, where Dolly the sheep was cloned in 1996. “You cannot directly extrapolate from mouse experiments to humans. Having a larger intermediate model is important.
The researchers used the gene-editing technique known as Crispr-Cas9 to produce a version of the gene that drives CLN1 in sheep.
“The sheep ovaries were taken from the slaughterhouses, the eggs were taken and fertilized. Crispr reagents were added to make the required changes in CLN1 and the eggs were then implanted into surrogate sheep,” Wishart explained.
Now the researchers had a group of sheep carrying the defective gene.
“They are asymptomatic carriers, like parents of children with Batten disease,” Wishart added. “From these, we could then breed sheep that have two defective copies. They develop a disease like these children and have become the subjects of our therapeutic trials.
Batten disease wreaks havoc on children because they lack an enzyme made by healthy CLN1 genes. This causes their body’s lysosomes, the parts responsible for recycling waste products that accumulate in cells, to malfunction.