Gene therapy could inform treatment for childhood dementia

Early studies of a rare and fatal childhood dementia have highlighted a novel gene therapy with encouraging results, paving the way for future treatment options.

Scientists at the Roslin Institute have used animal models to test a therapy for one of the fastest progressing types of Batten disease, also known as CLN1, a neurological condition in which affected children are missing a key protein that helps the brain clear away waste.

Children with this deficiency typically develop symptoms such as loss of vision and motor function in infancy, and rarely survive beyond 10 years of age. No effective treatment currently exists.

The therapy, developed by commercial collaborator Spark Therapeutics, uses a harmless virus to carry genetic instructions for the missing protein into the brain and the wider central nervous system.

Animal models

In studies in mice lacking the equivalent gene, this therapeutic approach led to long-term benefits, including extended lifespan, preserved neurological function, and protection against brain damage. 

Treated mice were almost indistinguishable from healthy controls for more than a year, the research team explains. This serves as an important indication that the therapy can prevent the rapid neurological deterioration usually seen in this form of Batten disease.

To assess whether the approach could work in larger mammal brains, a research team from the Roslin Institute has worked with Spark Therapeutics to deliver the therapy in healthy adult sheep. 

Using surgical techniques similar to those that would be applied in hospitals, the team demonstrated that the treatment reached widespread areas of the brain and spinal cord. The treatment was well-tolerated, with no adverse effects noted in the sheep.

Although more research is needed, these findings suggest that gene therapy for CLN1 Batten disease could one day be a viable approach in human patients, the team explains. 

Bridging studies

Experts also highlight the value of sheep models, which offer greater similarity to the human brain than rodents and may provide an ethically preferable alternative to companion animals and primate studies. Although the University of Edinburgh does not include such species in their human therapy development studies, these are part of many pre-clinical trials in the USA.

The study builds on previous work at the Roslin Institute, where researchers developed sheep carrying the equivalent genetic defect to children with the CLN1 form of Batten disease. These animals are now being used to study disease progression and test future therapies.

Although more research is needed before human trials can begin, these results represent an important step forward. Continued progress could eventually lead to treatments capable of slowing or halting the disease, hopefully adding years to the lives of affected children, the research team says.

This research was published in Molecular Therapy. The work was supported by Edinburgh Innovations, the University’s commercialisation service, and was carried out in collaboration with colleagues from the Centre for Clinical Brain Sciences at the University of Edinburgh, and the Centre for Systems Health and Integrated Metabolic Research at Nottingham Trent University. 

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