Thursday, January 18, 2007

Toward A Genetic Test For Parkinson's Disease

Molecular markers of early Parkinosn’s disease based on gene expression in blood.
Scherzer, C.R., A.C. Eklund, L.J. Morse, Z. Liao, et al. Proc. Nat. Acad. Sci.,104 (3), 955-960 (January 16, 2007).


Parkinson’s disease (PD) is a progressive neurodegenerative disorder
that is difficult to diagnose until significant cell loss has already
occurred in the substantia nigra, as evidenced by abnormally slow
movement and tremor. Even then, other neurological diseases may
confound a clinical diagnosis.

The
authors of this study provide a first-pass at identifying a set of
genetic markers for diagnosing PD. Their work entailed screening venous
blood of 31 PD patients and 35 controls, 18 of whom had other
neurological diseases such as Alzheimer’s disease and progressive
supranuclear palsy. The microarray analysis used more than 22,000
oligonucleotide probes to find differences in RNA content of the blood.
Eight unrelated genes that are expressed in the brain were identified,
including three implicated in PD: the vitamin D receptor, huntingtin
interacting protein 2, and a protein involved in dopamine transporter
endocytosis. The other five have not been associated with PD
previously.

A test of the biomarker’s accuracy found that there
was a significant difference between patients with PD and the normal
and disease controls. Those with a score in the highest third had an
odds ratio of 5.1 for PD, versus 1.9 for the intermediate third of
patients. (The lowest third was used as a reference group with an
assigned score of 1.)

The microarray analysis also identified
22 genes whose expression was altered in PD patients, but lacked
predictive power since they were found at abnormal levels in other
neurodegenerative diseases. Further investigation of these genes seems
warranted, as they may shed light on disease pathology. Indeed, one,
the heat-shock protein 70-interacting protein ST13 gene may afford an
opportunity to follow disease progression.

In all, this study
provides enticing leads to follow for the development of a
biomarker-based diagnostic test for Parkinson’s disease, as well as an
assay for assessing disease progression.
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Tags: progressive | NEUROLOGICAL | Genetic | disease | DIAGNOSE | Technology | Parkinson

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