Experimental Pill to Treat Parkinson’s Is Safe, Trial Finds

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An oral medication aimed at slowing the advance of Parkinson’s disease was well-tolerated in 150 people who took it over 28 days, according to clinical trial results published in Science Translational Medicine on Wednesday (June 8). The trial did not assess whether the drug affected the disease’s progress in humans. However, the study’s authors write that their experiments in animals and in cells suggest that the treatment may correct the dysfunction in cellular lysosomes that causes the disease.

“This is a very, very important step forward,” Patrick Lewis, a neuroscientist at the University of London’s Royal Veterinary College who was not involved in the research, tells Science.

Parkinson’s disease can occur when LRRK2 enzymes in the brain accumulate at such high levels that they damage lysosomes, organelles that remove toxins from the brain, reports the Financial Times. “Lysosomes perform a garbage disposal and recycling role for cells,” Carole Ho, Denali’s chief medical officer, tells the Financial Times. “If they are not working properly, toxic proteins build up and interfere with the proper functioning of cells in the brain.” 

Denali Therapeutics has developed two drugs, DNL201 and DNL151, that work by preventing the buildup of LRRK2 enzymes.

Previous tests of the experimental drugs raised concerns about potential side effects in humans, according to Science: animals given DNL201 displayed high levels of the protein dardarin, which caused the vesicles—small fluid-filled sacs inside cells—in their lungs and kidneys to swell.

The current study aimed to reduce the effects of dardarin build-up while preserving the therapeutic benefit of restoring lysosome function, according to Science. While the small study, which included mice, rats, macaque monkeys, and humans, did not evaluate the efficacy of DNL201 in slowing Parkinson’s, the study demonstrated that the drug boosted lysosomal function in animal models and didn’t cause noticeable side effects in humans or monkeys.

Because DNL201 has to be taken twice daily, Denali has decided to move forward with its companion drug, DNL151, which only requires a single daily dose, reports Science.

“It is a very exciting time for Parkinson’s research as we have now reached the point of clinically testing novel treatments that have been developed based on a better understanding of the underlying biology,” Simon Scott, deputy research director at Cure Parkinson’s, tells the Financial Times.