Bloomberg the Company

(Bloomberg) -- Two of Roche Holding AGs experimental drugs for Parkinsons disease caused lung toxicity in monkeys, researchers said, delivering a setback to one of the most promising pathways to a new type of treatment.

The findings will be a disappointment to advocates of Parkinsons research. The LRRK2 gene mutation gained attention after Sergey Brin, co-founder of Google Inc., disclosed in 2008 that his genetic code carries the flaw, which is associated with increased risk of Parkinsons. Brin has donated more than $100 million to find a cure for the disease.

Inhibition of the LRRK2 protein resulted in abnormal accumulation of compounds in specific cells that play a key role in many lung functions, including helping the organs inflate and deflate during breathing, according to the study run by Roches Genentech unit and published Wednesday in the journal Science Translational Medicine. The compounds were trapped inside the cells instead of being released into the lining of the lungs.

Were in a big bind, said Ryan Watts, director of neuroscience at Genentech. We want to make sure in patient populations that you have a safe drug to go into studies.

A link between mutations in the LRRK2 gene and Parkinsons disease was found in 2004. The mutation is only found in 2 percent to 5 percent of patients, according to the Michael J. Fox Foundation for Parkinsons Research, but it is one of the few direct causes that have been discovered for the disease, making it the focus of drugmakers efforts.

The foundation has poured at least $10 million a year for the past decade into research on the LRRK2 mutation, which it sees as one of the most promising therapeutic targets, said Chief Executive Officer Todd Sherer. He said Genentechs finding was unexpected.

The LRRK2 inhibitors, which are also in development by drugmakers Pfizer Inc. and Merck & Co., are seen as the leading hope for a disease-modifying drug. About 50,000 to 60,000 new cases of Parkinsons disease are diagnosed each year in the U.S., according to the National Parkinsons Foundation. The drugs currently on the market only treat symptoms and dont slow progression of the neurodegenerative brain disorder, which reduces a patients ability to regulate movements and emotions.

The Genentech scientists also saw liver toxicity in mice that were genetically engineered so they didnt produce the LRRK2 protein at all. While the liver problems werent seen in the monkeys, Watts said its possible liver damage would appear with long-term use.

Scientists had hoped an LRRK2 inhibitor could be given to early-stage patients or even healthy people to prevent the progression or start of the disease, Watts said. Since patients could end up using the drugs for decades, its especially important not to have toxic side effects, he said.

Despite the disappointing findings, the foundation and Genentech are continuing with their research plans for LRRK2 mutations.

Originally posted here:
Bloomberg the Company