Activating neurons with light restores movement in Parkinson’s model

Neurons
Carnegie Mellon and Pitt researchers are flipping certain neurons on and off in a bid to relieve symptoms of Parkinson's.

Deep brain stimulation can help control the involuntary muscle movements associated with Parkinson’s disease, but the effects of the therapy are not long-lasting. Scientists at Carnegie Mellon are developing a next-generation version of the therapy using optogenetics, a technique that flips certain cells on and off with light.

Neuroscientists at Carnegie Mellon and the University of Pittsburgh are reporting that when they used optogenetics to target two specific types of neurons in the brain, they were able to stop the abnormal movements associated with Parkinson’s in a mouse model. The effects lasted for at least four hours—much longer than traditionally used treatments, according to a press release.

Parkinson’s occurs when dopamine neurons die, causing the malfunctioning of the brain’s basal ganglia, which are responsible for producing voluntary movement. That’s why most Parkinson’s treatments target the basal ganglia.

Carnegie Mellon neuroscientist Aryn Gittis and her team wanted to know more about how the basal ganglia work, so they zeroed in on a specific structure in the region of the brain called the external globus pallidus (GPe). From there, they targeted two neurons: PV-GPe and Lhx6-GPe. They discovered that by using light to make PV-GPe neurons more active, they could stop abnormal behavior in the basal ganglia.

Parkinson’s researchers are eager to move beyond traditional dopamine-targeting treatments, and optogenetics is one of many ideas for doing just that. Last year, researchers at Caltech launched a new company, Axial Biotherapeutics, which is looking for new treatments for the disease in the gut microbiome. AbbVie and Eisai are working with startup BioArctic on an antagonist to the protein alpha-synuclein for the treatment of Parkinson’s. Meanwhile, Merck Serono spinout Prexton Therapeutics is in phase 2 trials of an mGluR4 positive allosteric modulator.

Optogenetics is making headway, too. Last September, Allergan shelled out $60 million for RetroSense Therapeutics, which is developing an optogenetics treatment for retinitis pigmentosa.

Gittis is hopeful her team’s results using optogenetics in mouse models of Parkinson's might lead to a longer-lasting therapy for Parkinson’s. “A major limitation of Parkinson's disease treatments is that they provide transient relief of symptoms,” said Gittis, assistant professor of biological sciences in the Mellon College of Science, in the release. “Symptoms can return rapidly if a drug dose is missed or if deep brain stimulation is discontinued."

The research was published in the journal Nature Neuroscience.

This story has been updated with further details on optogenetics.