Better ways to deliver drugs in more effective ways and to enhance the protection of neurons in Parkinson’s disease, including new drug combinations, are promising approaches in treating the disease, an Augusta expert told a national briefing Tuesday.
Still, there need to be better ways of identifying subtypes of the disease and finding animal models that better mimic them to spur future drug development.
Dr. Kapil Sethi, a professor of neurology and the director of the Movement Disorders Program at Georgia Regents University, held an online briefing for the Parkinson’s Disease Foundation on drugs in the pipeline for treating the disease.
Relatively few new therapies have been approved to treat the disease, in part because drugs that seemed to work in animals have often gone on to fail in human clinical trials, Sethi said.
“We’ve had trouble developing a faithful animal model,” he said, and listed more than a dozen compounds whose promise fizzled out. That is partly because of the wide range of symptoms and complications associated with the disease, Sethi said.
“Everybody has their own Parkinson’s disease,” he said, yet people are often lumped together in large clinical trials for testing. Still, there are more than 100 therapies in testing to treat the disease. Some focus on trying to slow the clinical progression and protect nerves.
One approach is looking at two areas very close to each other in the brain, one of which is damaged by the disease and the other not nearly as affected. In the damaged area, neurons switch from having sodium channels to calcium channels as people age, but that doesn’t seem to happen in the unaffected area, Sethi said.
“Maybe there is something about that calcium channel dependence that leads to the introduction of some toxic molecules into these cells or that mechanism itself is deleterious to the health of the cell,” he said.
In animals, giving a calcium channel-blocking drug seemed to cause the affected cells to revert and appears to be protective, Sethi said. High levels of urate, a salt of uric acid, can be harmful and cause diseases like gout. In Parkinson’s, it might not be so bad, Sethi said.
“If you have high urate, you are less likely to get Parkinson’s disease,” he said. “Urate has some antioxidative properties, but it may have other actions we don’t understand.”
One drug is actually trying to increase urate levels.
Many other approaches are seeking to prolong the benefits of the most effective Parkinson’s drug, levodopa, including a method already approved in Europe that would deliver a longer-acting form of the drug directly to the area of the small intestine where it is best absorbed. Better, longer-acting forms are on the near horizon, Sethi said.
“There seemed to be a little pause in new drug approvals for Parkinson’s disease,” he said. It is time-consuming and expensive to get drugs of that type to approval. “I think in the end patience will pay off. We will have drugs not only to slow down Parkinson’s disease progression but also to treat motor and nonmotor symptoms effectively.”