This Small Gene Edit in the Brain Could Stop Parkinson’s

A new study published in the journal Nature on Wednesday shows that gene therapy on mice could be used to boost the effects of existing drugs used to treat Parkinson’s disease, especially in late stages. And to boot, another arm of the study confirmed suspicions of how Parkinson’s starts, which could one day help scientists identify people who could be vulnerable to developing Parkinson’s five to 10 years before the onset of symptoms.

Parkinson’s disease is thought to arise due to the loss of neurons in the brain that produce dopamine, a neurochemical that plays many different roles as a signal to other nerve cells. Dopamine is probably best known as the “feel-good” chemical that’s associated with pleasure and reward. But it’s also critical in motor control. As these neurons fail and die, dopamine levels tank, and Parkinson’s symptoms can worsen.

One way doctors treat Parkinson’s is through prescribing a drug called levodopa, which the body’s neurons can convert into dopamine to restore levels to some degree of normalcy. But as the disease progresses, more and more neurons die before they can run this conversion, severely impeding the efficacy of levodopa in late-stage Parkinson’s.

The key to treating Parkinson’s might be in saving these neurons and restoring them to normal function. One theory suggests these neurons stop releasing dopamine because of a specific failure in their mitochondria (which generate energy for the cell). A solution could be: Save the mitochondria, save the neuron, prevent dopamine levels from falling—and stop Parkinson’s.

Gene therapy—in which doctors edit specific parts of one’s DNA to treat or cure a disease—is one way to accomplish this. “These approaches have such remarkable power,” James Surmeier, a neuroscientist at Northwestern University and a coauthor of the new study, told The Daily Beast. “In our case, we took a gene therapy that had been tried and stopped in humans ‘off the shelf,’ to test the hypothesis that it might work in a different brain region.”

In the new study, Surmeier and his colleagues genetically engineered mice to disrupt mitochondria function in a region of the brain called the substantia nigra—home to neurons that die first during Parkinson’s. This specific mitochondrial disruption didn’t kill the neurons, but it did stop dopamine production, so the mice essentially emulated the disease. This finding was proof that mitochondrial dysfunction in neurons that make dopamine “is sufficient to trigger a cascade of events that looks remarkably like the human [Parkinson’s] disease,” said Surmeier.

The team then used its newfound gene therapy technique to create a new biochemical pathway in substantia nigra neurons that allowed the mice neurons to convert levodopa to dopamine, even if the mitochondria function was still impaired. Motor disabilities in the mice were “significantly alleviated,” the authors wrote.

“This discovery helps us construct a causal chain of events that could explain the long course of the disease,” said Surmeier. “It points to ways in which we might slow or stop disease progression.”

In addition, having a clearer model of how Parkinson’s disease progresses provides clues for what doctors could look for before symptoms even show up—by as much as 10 years in advance. A test for, say, mitochondrial failure in substantia nigra neurons would be a very useful early warning for patients.

Though the new findings are in mice, Surmeier and his team are already on the way to moving this treatment into human clinical trials as quickly as possible. “The gene therapy has already been tested in humans and is safe,” he said. It follows a surgical approach similar to placing brain stimulation implants, which is done routinely for late-stage Parkinson’s patients in hundreds of hospitals. “We’re in discussions now with potential partners that could fund the effort.”