A drug used for Parkinson’s disease repairs nerve damage caused by multiple sclerosis, according to a study led by scientists at The Scripps Research Institute. If it works in humans, it will be the first drug to reverse the course of the disease.
The animal study could be translated into a clinical trial within two years, a scientist who led the study says. But safety issues with the drug, benztropine, need to be resolved first.
Multiple sclerosis is an autoimmune disease that erodes a protective sheathing around nerves called myelin. Patients with the disease gradually lose sensation and movement. Drugs for the disease suppress the immune reaction but cannot repair the lost myelin.
In a study performed in rodents, benztropine regenerated the myelin sheathing. The drug was tested in two mouse models of multiple sclerosis, which impairs movement and sensation. Mice injected with benztropine regained movement. (For Parkinson’s disease, the drug is taken orally and by injection).
The study was published Wednesday in the journal Nature. Luke L. Lairson, Peter G. Schultz and Brian R. Lawson were senior authors. Vishal A. Deshmukh was first author. All are with Scripps. It can be found online at utsandiego.com/msdrug.
“This looks very, very promising,” said Barbara Ranscht, who studies multiple sclerosis at the Sanford-Burnham Medical Research Institute. “I think this will give hope to a lot of MS patients.”
Ranscht, who was not involved in the study, said she was impressed by the drug’s efficiency in inducing new myelin formation and alleviating MS symptoms in the mouse models.
However, more work needs to be done to improve safety before clinical trials can begin, Lairson said. So multiple sclerosis patients should not take the drug on their own or they could harm their health.
Benztropine can induce psychiatric problems and at high doses can actually cause MS-like symptoms, Lairson said. So more research needs to be done to improve safety. This includes finding the proper dose.
It’s possible that pairing the drug with an immune suppressant could reduce the amount of drug needed, Lairson said. Also, it may be possible to find a similar compound that’s safer.
If all goes well, a candidate drug for a clinical trial could be identified in a year, Lairson said. The best-case scenario would be using benztropine with no modifications.
“If we need to optimize the compound, or use a different compound, we could be five years off,” he said. “But if everything works, we could be in a trial within a year or two.”
An accompanying review article in Nature said the study “may finally raise the hope of myelin repair.”
The article said benztropine’s severe side effects remain a concern.
“But the present results will motivate the group to search for drug variants that maintain benztropine’s virtues — its myelin-repairing activity and its ability to cross the blood-brain barrier — but lack its dark side,” stated the review article.
The researchers found the drug by testing 100,000 molecules in a laboratory that Scripps shares with the California Institute for Regenerative Medicine, the state’s stem cell agency. They were looking for a compound that could produce myelin-making cells called oligodendrocytes from precursor cells. These oligodendrocyte precursor cells are present in multiple sclerosis patients, but don’t turn into the myelin-making cells.
“There is a pool of oligodendrocyte progenitors that sit around the lesion, but they don’t do anything,” said Ranscht, of Sanford-Burnham. “There’s a block on these cells. They found a drug to unblock that. And then the oligodendrocytes precursors can go into the differentiation process, and then they can remyelinate.”
Of all the comounds screened, benztropine turned out to be especially effective in producing oligodendrocytes, as well as preventing and stopping the autoimmune reaction in the mouse models. Moreover, even a small amount of benztropine amplified the effectiveness of immunosuppressant drugs, so that smaller doses could be given. If the research applies to humans, the side effect of these drugs could be reduced.
The drug readily penetrates the blood-brain barrier, which Ranscht said is a nice advantage. The barrier keeps many drugs out of the brain and spinal cord. Benztropine is a relatively small molecule, which makes it easier to get there.