Conclusions and Implications for Translational Research
More than 40 years ago, Hornykiewicz discovered the selective dopamine deficiency in PD and, together with Birkmayer, introduced the first form of neurotransmitter-replacement therapy, which remains the basis of symptomatic treatment in PD to this day. The discovery of a familial PD-associated gene in 1997 and the ensuing breakthroughs heralded the beginning of a new era. The PD field now enjoys an embarrassment of riches in genetic leads that also represent a mandate for translational research success. In the clinic, two immediate goals need to be met.
First, it is necessary to develop a widely available, inexpensive biomarker for PD that improves diagnostic accuracy by all practitioners. Such a test (or combination of tests) should ideally capture individuals at risk during their presymptomatic period, distinguish patients with classical PD from those with other disorders in their symptomatic stage, and accurately reflect disease progression, or its arrest following successful intervention.
Second, recent pathogenetic insights need to be urgently translated into cause-directed therapy for neuropreventive treatment during the presymptomatic phase of PD and neuroprotection of residual at-risk cells in the symptomatic stages.
For pharmacological purposes, the plethora of research developments since 1997 has generated two intriguing leads. Lowering the SNCA steady-state level in vivo (in particular in individuals with elevated levels of SNCA) and increasing the expression of Parkin (and possibly the DJ1 and PINK1 proteins) in the aging human brain could help to slow PD progression in our already diagnosed patients and, ideally, delay disease onset in high-risk individuals.
Note Added in Proof
The c.6055G→A mutation has been found to be a frequent cause of PD in certain ethnic populations, accounting for as many as 18% of cases in Ashkenazi Jews and 37% of cases in North African Arabs.
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We thank our patients and their families for encouragement and support. The authors wish to express their gratitude to their colleagues M Farrer, A Lang and L Sudarsky for critical comments on earlier versions of the manuscript.Funding information
CK received support through a Lichtenberg Grant from the Volkswagen Foundation, the Deutsche Forschungsgemeinschaft, and a Research Grant from the University of Lübeck; MGS received support from the National Institute of Neurological Disorders and Stroke/National Institutes of Health, Michael J Fox Foundation, and Multiple System Atrophy Fund at Brigham and Women's Hospital.
Christine Klein, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany, Email: firstname.lastname@example.org
Nat Clin Pract Neurol. 2006;2(3):136 © 2006 Nature Publishing Group
Cite this: The Genetics of Parkinson Disease: Implications for Neurological Care - Medscape - Mar 01, 2006.