The Florida branch of The Scripps Research Institute is touting some new advances related to Parkinson's disease. Researchers say they have been working on new therapies that can precisely hit pathways critical for the death of brain cells, a hallmark of the disease. And they're now fine tuning their work by focusing on the oral bioavailability of their new drug candidates.
The therapies are designed to protect mitochondria, which help protect brain cells, by targeting a slate of enzymes known as JNK1, JNK2 and JNK3. These enzymes spur oxidative stress and programmed cell death, as seen in Parkinson's and Scripps' new drugs block the threat. And their therapies are designed to be highly specific to isoforms.
In JNK3, for example, the scientists say that a single amino acid was linked to target selectivity. And by carefully focusing their drugs on small targets like that, they hope to steer clear of side effects that would threaten their use in patients.Philip LoGrasso
"These are the first isoform selective JNK 2/3 inhibitors that can penetrate the brain and the first shown to be active in functional cell-based tests that measure mitochondrial dysfunction," said Philip LoGrasso, a TSRI professor who led both studies. "In terms of their potential use as therapeutics, they've been optimized in every way but one--their oral bioavailability. That's what we're working on now."
As is often the case in CNS research, the investigators believe that their drugs could relate to other brain diseases, including Alzheimer's and Lou Gehrig's disease.
The studies were published in the Journal of Medicinal Chemistry and Scientific Reports.
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