Parkinson’s drug may help brain injuries: report

Parkinson’s drug may help brain injuries: report

Daily doses of a drug used to treat Parkinson’s disease significantly improved function in severely brain-injured people thought to be beyond the reach of treatment, scientists reported Wednesday, providing the first rigorous evidence to date that any therapy reliably helps such patients.
The improvements were modest, experts said, and hardly amounted to a cure, or a quick means of “waking up” someone who has long been unresponsive. But they were meaningful, they said, and if replicated would give rehabilitation doctors something they have never had: a standard treatment for injuries that are not at all standard or predictable in the ways they affect the brain.
Some 50,000 to 100,000 Americans live in states of partial consciousness, and perhaps 15,000 in an unresponsive “vegetative” condition. According to the Department of Defense, more than 6,000 veterans have returned with severe brain injuries since 2000 and would potentially benefit from this therapy. The new report, appearing in the New England Journal of Medicine, gives doctors a solid basis to address such injuries, if not yet a predictable outcome.
“This study puts the traumatic brain injury field on the first step of the ladder to developing scientific treatments. We’ve been trying to get there for a long time,” said Dr. Ramon Diaz-Arrastia, director of clinical research at the Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, who was not involved in the research. “And there’s no reason to doubt that this therapy would also be effective in people with less severe brain injuries” than in the study.
“Hope is critical, and false hope is cruel for families dealing with this,” said Susan Connors, president and chief executive of the Brain Injury Association of America, in Vienna, Va. The new findings, she added, are “a little piece of hope, the real kind.”
Doctors have long experimented with the Parkinson’s drug – amantadine hydrochloride – as well as many others to treat severe brain injuries, with mixed and uncertain results. Previous studies of amantadine suggested some benefit, but the numbers were small and experts were unsure of the results.
For the experiment, a consortium of researchers from 11 clinics enrolled 184 patients who each recently had a traumatic brain injury from a car accident or from blows to the head. Some were in a vegetative state, breathing, their eyes open during waking, but unresponsive to commands or prompts. Others were in what is known as a minimally conscious state, able to track objects and follow commands once in a while, but not predictably.
The research team, led by Joseph T. Giacino of the JFK Johnson Rehabilitation Institute in Edison, N.J., and Dr. John Whyte of the Moss Rehabilitation Research Institute, near Philadelphia, divided the patients into two groups, carefully matched for the severity of their injuries. Members of one group got two doses of amantadine a day, given through their feeding tubes. Members of the other group each received placebo pills.
The study was “blinded,” meaning that the therapists providing the usual daily care – moving limbs, stimulating the senses and giving medical support – did not know who was on the drug and who was not.
After four weeks, the researchers analyzed the progress of the patients, using a standard scale that rates responses like eye opening, motor control, and need for help eating and bathing. The scale ranges from zero, for no disability, to 29, for a state of total unresponsiveness, and is scored regularly at bedside.
Almost all of the patients improved somewhat during the four weeks. This was expected; their injuries were recent, and in the first year after a traumatic wound most people recover some function, even if they do not always regain full awareness later on, scientists say.
But the group receiving amantadine showed more improvement, by two points on the disability scale. Two points is not a dramatic difference, but it occurred in just a month, a short period of time in terms of recovery.
“The main finding is that on every single behavioral domain measured, we had a higher incidence of recovery in the amantadine group than in the placebo group,” said Giacino, who is now at Harvard’s Spaulding Rehabilitation Hospital.
When doctors took patients off the drug, the rate of recovery slowed.
“In the next two weeks, the placebo group caught up,” Whyte said. “So we know that the drug accelerates recovery, but we can’t say whether it alters the trajectory entirely.”
The people on the drug showed no adverse effects, Whyte said.
Among other effects, amantadine boosts the activity of dopamine, a chemical messenger that is highly active in the frontal areas of the brain, behind the forehead, which control attention and help plan and execute deliberate actions and responses. These areas are at least partially damaged or off-line in people with severe brain injuries.

Some experts said that the study, funded by the National Institute on Disability and Rehabilitation Research, could be a turning point in the understanding and treatment of people with severe traumatic brain injuries. The 11 centers were located around the world, in Germany, Canada and Denmark, as well as Indianapolis and Jackson, Miss., and the collaboration produced a positive result.

That in itself – a standard therapy – may give family members, doctors, and policymakers leverage to get treatment covered by insurers. Many thousands of people with such severe injuries lie trapped in partial states of consciousness, in nursing homes and living rooms, with no access to rehabilitation.

“I see this as a tipping point for the entire field,” said Dr. Nicholas Schiff, a neuroscientist at Weill Cornell Medical College in New York, who was not involved in the study. “If this drug works, then other things will too, in various combinations, and we can begin to develop a medical model for treatment.”

Updated : 2021-03-07 17:25 GMT+08:00