Skip secondary menu

‘Gene Chip’ Study Could Lead to Blood Test for Parkinson’s


For release: Monday, April 2, 2007

A new study has revealed 30 genes whose activity levels are altered in the blood of people with Parkinson’s disease (PD), paving the way for a blood test and a better understanding of what causes the disease.

“It will take time to develop a clinically useful blood test for PD, but our results show that it’s feasible,” said the study’s lead author Clemens Scherzer, M.D., a neurologist at Brigham and Women’s Hospital and Harvard Medical School in Cambridge, Massachusetts. The study was supported in part by the National Institute of Neurological Disorders and Stroke (NINDS), and was published in the Proceedings of the National Academy of Sciences.*

At present, PD is diagnosed based on its canonical symptoms – involuntary shaking, slowness of movement, stiffened muscles, and impaired balance – but those symptoms mean that the disease has already caused substantial damage to the brain.  A blood test built around one or more of the 30 genes could be used to detect PD and begin treatment before the onset of symptoms, Dr. Scherzer said.  The genes also could yield clues into the causes of PD, which are unknown in most patients.

PD attacks cells nestled in the substantia nigra, a structure near the base of the brain.  By the time symptoms of the disease appear, as many as 70 percent of these cells – which produce the chemical dopamine – have already died, said Dr. Scherzer.  The drug levodopa, a precursor of dopamine, provides some relief from symptoms, but there is no drug proven to slow the loss of dopamine-producing cells.  A pre-symptomatic test based on genetic probes could be the key to developing such a drug, since it would allow recruitment of patients into clinical trials before the disease has ravaged the brain.

In his study, Dr. Scherzer developed a prototype test – years away from clinical use – which shows that eight of the 30 genes are activated in an abnormal pattern that is reliably associated with PD.

Dr. Scherzer identified the 30 genes by using microarrays to probe blood for RNA – the molecule a gene makes when it’s “turned on.”  Microarrays, also called “gene chips,” are tiny glass squares coated with thousands of gene fragments, each one in a precisely charted location.  If a mixed soup of RNA (in this case, from blood) is washed over the chip, the RNA molecules sort out and stick to their matching gene fragments on the chip, yielding a snapshot of gene activity.

In one part of his study, Dr. Scherzer performed a microarray analysis on blood from about 60 people, half of whom had PD while the other half were healthy or were affected by a different neurological disease.  A computer sorted through the data, found genes whose activity went up or down in PD, and examined them in different combinations, looking for a “template” of gene activity in PD.

What emerged, said Dr. Scherzer, was “a set of eight marker genes whose activity was tightly correlated with PD, and not with other diseases.”  If a gene was taken away from the set or added to it, the correlation became weaker, he said.

In another part of the study, Dr. Scherzer compared microarray data only from people with PD and healthy controls, looking for individual genes whose activity changed sharply in PD.  That analysis revealed a distinct set of 22 genes that are less active in the blood of people with PD.  Dr. Scherzer was able to detect a drop in some of the genes’ activity by using a relatively conventional blood test (designed to measure RNA from a single gene) instead of using a microarray.

Among the total set of 30 genes found, a few have been implicated in other neurological diseases.  This could mean that changes in their activity are a cause of PD, rather than an effect of the disease.  Mutations in one of the genes, called LRPPRC, underlie French-Canadian-type Leigh syndrome, a childhood-onset disease that can cause neurodegeneration in the brainstem.  The gene is needed by mitochondria – cellular energy factories that appear to work less efficiently in the brain cells of people with PD.

Dr. Scherzer said he plans to investigate whether abnormalities in LRPPRC and the other 29 genes affect disease onset or progression in animal models of PD.  He’ll also focus on validating a clinically useful blood test for PD.

The test – whether it involves microarray analysis or more conventional techniques – “needs to be refined and go through large-scale prospective trials,” he said.  “Ultimately, we hope it can be used on healthy seniors to detect those who are at high risk for developing PD and those who are not.”

*Scherzer CR et al.  “Molecular Markers of Early Parkinson’s Disease Based on Gene Expression in Blood.”  Proceedings of the National Academy of Sciences, January 16, 2007, Vol. 104(3), pp. 955-960.

-By Daniel Stimson, Ph.D.

Last Modified April 2, 2007