Genes, immunity & Parkinson's disease

According to researchers at Johns Hopkins from the Centre for Inherited Disease Research, a gene in the human leukocyte antigen (HLA) region was strongly linked with Parkinson's disease; this region contains a large number of genes related to immune system function. Acclaimed journal Nature, where the study was published says that inflammation is not the result of the PD but is involved as a player in its origin.

Kimberly Doheny said, "This is an exciting finding from a genome-wide association study (GWAS) which is completely hypothesis-independent and bias-free, based solely on looking at the whole genome and finding out what genes might be related to Parkinson's." Haydeh Payami agreed saying, "This finding anchors the idea of immune system involvement in genetics and brings it out to the forefront in terms of where research should be directed."

This study shows that Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are protective against Parkinson's disease but the benefit is selective to some patients. The amount of risk reduction conferred by NSAIDs may vary widely depending on genetic differences, say the researchers. The new data is published in Nature Genetics.

Drugs for PD

In another study published in August issue of Nature Medicine, researchers from Johns Hopkins have shown that using specific drugs can protect nerve cells in mice from the lethal effects of Parkinson's disease.

These drugs block a protein that, when altered in people, leads to Parkinson's disease. This protein LRRK2 (pronounced lark 2) is overactive in some Parkinson's disease patients and causes the shrinkage and death of the brain and nerve cells. The exact link between the protein and PD is unknown.

For this study the scientists speculated that blocking LRRK2 from acting might protect nerve cells. The research team tested drugs that were commercially available and known to prevent proteins such as LRRK2 from acting and adding chemical phosphates to other proteins. Out of 70 drugs tested, eight were found to block LRRK2 from working.

Two of these eight drugs managed to go over to the brain crossing the blood brain barrier that blocks most drugs from entering the brain. Scientists injected these two drugs twice daily into mice engineered to carry Parkinson's-causing LRRK2 changes in their brain. After three weeks, they examined the mouse brains to see if nerve cells had died. One drug provided almost complete protection against nerve cell death, and another had about 80% fewer dead cells than in mock treated mice.

Ted Dawson, professor of neurology and physiology and scientific director of the Johns Hopkins Institute for Cell Engineering said, "This data suggests that if you were to develop a safe drug, then you could potentially have a new treatment for Parkinson's disease patients with LRRK2 mutations." "One could envision generating compounds around that core structure to develop a relatively selective and potent inhibitor of LRRK2," Dawson said.

Dawson's team was working in collaboration with researchers at Southern Methodist University to design more-specific inhibitors of LRRK2, and the group is aiming at licensing this technology. The drugs' approval by the FDA for use in humans may still take years.

"We're curing Parkinson's disease in a mouse, and now we have to discover drugs that actually work in human neurons. Then we'll hopefully be able to make the leap forward to get a treatment to work in humans," Dawson said.