Genetic Insights into Parkinsons Disease

diagram demonstrates how the LRRK2 gene is related to kinase activity and neural cell toxicity.
The diagram demonstrates how the LRRK2 gene is related to kinase activity and neural cell toxicity. Credit: Ted M. Dawson/Johns Hopkins

A chronic disorder of the central nervous system, Parkinson’s Disease (PD) is currently treated with drugs that may slow progression of its physical symptoms – including tremors, impaired balance, and rigidity – but lack significant effect on the progression of the disease itself. Ted Dawson and members of his research team at Johns Hopkins have been at the forefront of research identifying the role and function of genes in the pathogenesis of PD for years.

In the last decade, several important genes and their associations with PD have been discovered at a rapid pace, offering hope to patients who suffer from this common neurodegenerative condition. Dawson and others are investigating the molecular mechanisms of how genetic mutations cause PD in order to develop and test new molecular drugs that slow or halt disease progression.

Dawson and team recently published work in Nature Neuroscience on the mutant LRRK2 gene, which causes familial PD and some cases of sporadic PD. The work demonstrates that alteration to the mutant LRRK2 gene can reduce kinase activity and the neuronal toxicity that leads to cell death. The team is working on designing and testing inhibitor molecules that can demonstrate similar outcomes. This is but one example of promising PD therapeutics in development; many more are already in clinical trials.

What does the future hold for Parkinson’s disease? Dawson says that novel therapeutics that treat PD by modifying the disease 10-20% should be publicly available within three to five years.

β€œTen years from now, we should have therapeutics that can slow the disease down by a decade,β€œ says Dawson. β€œWe will definitely be able to slow or halt disease progression, but it may prove difficult to eradicate the disease completely.β€œ

Dawson is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and professor of neurology and neuroscience at Johns Hopkins, director of the Parkinson’s Disease Research Center, director of the Movement Disorders Center, director of the Neuroregeneration and Repair Program of the Institute for Cell Engineering, and faculty member of the Institute for NanoBioTechnology.

The research is funded by the National Institutes of Health, the Lee Martin Trust, the Sylvia Nachlas Trust, the National Parkinson Foundation, and the Michael J. Fox Foundation.

Citations: W. W. Smith, Z. Pei, H. Jiang, V. L. Dawson, T. M. Dawson, and Christopher A. Ross. Kinase activity of mutant LRRK2 mediates neuronal toxicity, Nature Neuroscience 9: 1231-1233 (2006).

J. M. Savitt, V. L. Dawson, and T. M. Dawson. Diagnosis and treatment of Parkinson disease: Molecules to medicine, The Journal of Clinical Investigation 116:1744-1754 (2006).

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