Studies on gene-edited sheep could help find cure for Batten disease
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Although there is no cure for Batten disease, healthcare providers have been focusing on the treatment of symptoms to make life easier for the carriers of the defect gene.
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Dolly; the first-ever cloned sheep
A team of US and UK experts published research in the Journal of Clinical Investigation in which they detailed the successful trials carried out on gene-edited sheep to alleviate symptoms of Batten disease. It is hoped that this research might pave the way to develop a drug for humans suffering from the illness.
Batten disease is a group of fatal genetic disorders that is passed down through families via a genetic mutation.
Although there is no cure for Batten disease, healthcare providers have been focusing on the treatment of symptoms to make life easier for the carriers of the defect gene.
Some of the symptoms children experience as a result of this illness range from seizures to vision loss, problems with thinking and movement, and eventually, death.
Initial experiments were carried out with the cooperation of colleagues at Collaborations Pharmaceuticals with lab trials on mice who presented one form of Batten disease, known as CLN1 disease, which could be treated with a missing enzyme.
Project leader Professor Tom Wishart, of Edinburgh University’s Roslin Institute, where cloning techniques were used to create Dolly the Sheep in 1996, said, "That was encouraging but we needed to test the treatment in larger brains with a structure more like those of a child."
"You cannot extrapolate straight from mouse experiments to humans. Having an intermediate larger model is important," he added.
The team of experts used the gene-editing technique Crispr-Cas9 to create a normal version of the defunct gene responsible for CLN1 in sheep. They were then able to create a flock of lambs that carry a single functional copy of the CLN1 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."
The lack of an enzyme produced by healthy CLN1 genes is the reason why Batten disease develops in children. The enzyme is crucial for enabling lysosomes to recycle waste material that builds up in cells.
Although the research on mice showed that injecting the missing enzyme into the brain produced noticeable improvements, proceeding with trials on humans was not deemed practical or safe, according to the team.
Another project leader, Professor Jonathan Cooper of Washington University School of Medicine in St Louis, said, “You can miss two crucial issues. How to deliver the drug to the right place in a bigger brain and how to scale up dosing.”
Test results that were conducted on half-dozen sheep from the Roslin flock with two faulty CLN1 genes revealed many hallmarks of the disease that affects humans. Improvements in their disease could clearly be observed by the team.
“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.”
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