Parkinson's Disease and a Potential Genetic Cure

Gene therapy for Parkinson's Disease. Getty Images Credit: Andrew Brookes

There is, as yet, no cure for Parkinson's Disease (PD). But significant progress has recently occurred in the search for a cure. In the past 10 years or so, several forms of hereditary PD have been discovered and the gene defects responsible for these forms of PD have been identified and studied. This discovery of genetic forms of the disease can be considered a breakthrough discovery in the search for a cure of PD because scientists can use the genes in question to search for the root causes of the disease.

For the record, the genetic defects that cause hereditary forms of the disease include mutations (changes in the chemical make-up of the gene) or duplications of portions of the gene in the question. The genes under investigation include the alpha-synuclein gene, the ubiquitin-C-terminal hydrolase-L1 (UCH-L1) gene, the leucine-rich repeat kinase (LRRK)2 genes, and the Parkin, PINK1, DJ-1 and the ATPase13A2 genes.

Now, of course, all of these names of genes may just sound like a meaningless foreign language to you. But I assure you that their discovery will lead to significant progress in the search for a cure for PD.

Repairing Genetic Defects That Can Cause Parkinson's Disease

We now know that certain types of genetic defects on certain genes can cause PD. That means that if we can repair the genes in question, we can prevent or potentially even cure the disease. There has been some work in this area already and some exciting projects are underway. This whole area of investigation is called gene therapy or genomic medicine. To date, introduction into the brain of a rat (a rat that has damaged dopamine cells) of a viral agent that expresses human Park1 into a rat model of PD resulted in protection from dopamine cell loss and Parkinson's like behavior in the rat. Of course, showing improvement in rat models of PD is a long way from showing that the same thing can happen in the human brain.

How Genetic Malfunctions Can Cause Hereditary Forms of Parkinson's Disease

Studies of the genetic defects that cause hereditary forms of PD have demonstrated that PD can result when one of multiple processes breaks down. These processes ultimately lead to cell damage in the brain. The first process concerns breakdowns in quality control processes for handling protein production in the brain. Proteins are the building blocks of all the tissues in your body.

So when the production process for protein manufacture breaks down, little clumps of ill-formed proteins begin to accumulate in cells, and in the case of alpha-synuclein, contribute to the formation of Lewy bodies. Research experts are still investigating the role of these Lewy bodies in the development of Parkinson's disease, but one theory suggests that protein aggregation interferes with the normal operation of the cell and dysfunction ensues. Another problem caused by gene defects that lead to hereditary forms of PD is known mitochondrial dysfunction. The mitochondria are little organelles in your cells that are responsible for producing energy for the body. A byproduct of mitochondrial operations is the production of free radicals -- little molecules that can hurt dopamine-producing cells. When mitochondria are operating normally, these free radicals are scavenged up and neutralized. But when mitochondria are not operating normally, the free radicals build up in the brain and damage dopamine-producing cells.

Finally, gene defects that lead to PD have also been found in so-called kinase proteins. These proteins have multiple functions in the cell, and researchers are still trying to understand how the gene changes cause PD.

Denise M. Kay, Jennifer S. Montimurro and Haydeh Payami. Genetics. In: Parkinson’s Disease: Diagnosis and Clinical Management: Second Edition Edited by Stewart A Factor, DO and William J Weiner, MD. 2008 Demos Medical Publishing.

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Article Sources
  • Andrew J. Lees, The Parkinson chimera. Neurology 2009;72;S2-S11; Mochizuki H. Gene therapy for Parkinson's disease. Expert Rev Neurother. 2007 Aug;7(8):957-60.