This column is written by experts in the medical field and focuses on current health, medical and research issues and developments.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the United States after Alzheimer’s disease. Each year, more than 50,000 new cases are reported; roughly half a million Americans have the condition.
The cause or causes of PD are not known, but there is a genetic component. In an effort to better understand that aspect of PD – and perhaps more fully illuminate the disease in general – a new nationwide study has just been launched, part of the ongoing Parkinson’s Progression Markers Initiative funded by The Michael J. Fox Foundation.
The University of California, San Diego School of Medicine is one of 18 official sites that will recruit and study eligible patients over the next two years. We asked Dr. Douglas Galasko, professor in the UC San Diego department of neurosciences and the Shiley-Marcos Alzheimer’s Research Center, to explain what’s known about the genetic risks of PD and what researchers hope to discover.
Q: Only a small minority of Parkinson’s cases – 5 to 10 percent – are currently believed to be genetic in nature. How does this new study, which looks specifically at persons with two distinct gene mutations, relate to the overall effort to better understand and treat Parkinson’s?
A: There are now more than 10 genetic risk factors associated with Parkinson’s disease, although this accounts for only 10 to 15 percent of patients. This new study focuses on people with mutations in two genes: SNCA and LRRK2.
These genes and the proteins that they encode are important in Parkinson’s disease in general. SNCA, or alpha-synuclein, is a protein normally found at synapses of nerve cells and it forms aggregates that contribute to damage to vulnerable nerve cells in people with Parkinson’s. Mutations in the SNCA gene are rare, and have been used to develop models for Parkinson’s, such as cells and transgenic mice that can help us understand the mechanisms of disease and to screen for new drugs.
Mutations in LRRK2 are more common in people of a particular ethnic background, in particular Ashkenazi Jews and people from North Africa, where they may account for 15 to 20 percent Parkinson’s disease patients. Gene changes in LRRK2 also occur in other ethnic population groups, but less commonly. LRRK2 is also being used to develop disease models.
As an analogy to help illustrate the potential value of studying people with genetic forms of common disorders, it was a rare set of families with increased cholesterol and premature heart disease due to a genetic mutation that provided the background leading to development of statin drugs.
By studying people who carry genes that predispose them to Parkinson’s, we hope to map changes in the brain and the body that may precede the movement problems typical of Parkinson’s disease, opening a window for early intervention. For example, we know that some people with Parkinson’s have an unusual sleep problem, called REM Sleep Behavior Disorder or RBD in which they seem to act out their dreams during sleep. RBD may precede Parkinson’s by five years or more.