Protein slows brain atrophy in mice

NORTHWESTERN (US) — A protein that promotes the growth of neurons and blood vessels may halt the spread of a brain disease that ravages the cerebellum.

The disease, spinocerebellar ataxia type 1, typically strikes people in their 30s and 40s and causes degeneration of the part of the brain that helps coordinate movement. As the disease progresses over 10 to 20 years, patients eventually die from aspiration or infectious pneumonia.

The disease is caused by a mutation in the protein ataxin-1, which plays a role in regulating a protein called vascular endothelial growth factor or VEGF.


As reported in Nature Medicine, when scientists replenished VEGF in the brains of mouse models, the brains—which had showed atrophy in the cerebellum—began to appear more normal, with an increase in connections between neurons. The mice also had improved balance.

“If you give VEGF early in the disease, you prevent degeneration later in life,” says Puneet Opal, associate professor of neurology and of cell and molecular biology at Northwestern University, who also treats ataxic patients.

“We think VEGF increases the blood vessels in the brain but also directly prevents neurons from dying. These results hold the potential for future therapy.”

Because patients are born with the mutation for the disease but don’t show signs of it until midlife, indications are that the aging process may play a role in development of the disease, Opal says.

“There could be a connection between a patient’s genetic mutation and their blood vessels not keeping up as they age. When we delivered VEGF to the brain and increased blood vessels, the disease stopped progressing in mice.”

The study was funded by the National Institutes of Health, the National Ataxia Foundation, the National Organization for Rare Disorders, and the Brain Research Foundation.

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