Two of Roche's Experimental Parkinson's Drugs Caused Lung Toxicity in Monkeys

Published: Feb 09, 2015

Two of Roche (RHHBY)'s Experimental Parkinson's Drugs Caused Lung Toxicity in Monkeys
February 6, 2015
By Krystle Vermes, BioSpace.com Breaking News Staff

Two experimental drugs designed to treat Parkinson’s disease from Roche Holding AG have now been shown to cause lung toxicity in monkeys. The news broke on Feb. 4 after researchers confirmed that the drugs, which inhibit the LRRK2 protein, were linked to lung complications, according to Bloomberg.

The LRRK2 gene mutation has been under the spotlight since 2008 when Google Inc. co-founder Sergey Brin noted that his genetic code contains the flaw, increasing his risk of Parkinson’s disease. He has since donated $100 million to find a cure.

In experiments, the inhibition of the LRRK2 protein resulted in the accumulation of compounds in specific cells that play a key role in several lung functions. Compounds were trapped inside of cells, rather than being released into the lining of the lungs.

The Michael J. Fox Foundation for Parkinson’s Research has donated $10 million over the past decade to research on the LRRK2 protein. However, the link between the LRRK2 gene and Parkinson’s disease has only been found in up to 5 percent of patients.

Roche is not the only company working on drugs that target Parkinson’s disease -- Pfizer Inc. and Merck & Co. are also developing similar LRRK2 inhibitors.

LRRK2’s Impact on the Brain
A study published in 2014 looked at how the LRRK2 protein may impact brain cells in patients with Parkinson’s disease. Researchers were able to determine that mutations may increase the rate at which LRRK2 tags ribosomal proteins, which could cause the development of too many proteins. In turn, this can result in excessive cell death.

“For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson’s disease,” said Margaret Sutherland, a program director at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke. “This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson’s disease.

LRRK2 gene mutations are thought to be the leading cause of Parkinson’s disease, although an exact cause has yet to be determined. The most common LRRK2 mutation, known as G2019S, is thought to be responsible for the disease in up to 40 percent of patients of North African Arabic descent.

“Our results support the idea that changes in the way cells make proteins might be a common cause of Parkinson’s disease and possibly other neurodegenerative disorders,” said Ted Dawson, who led the study.


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