3 June 2012
Technion researchers from the Rappaport Faculty of Medicine have identified five genes that predict Parkinson's disease, reports the scientific journal Molecular Neurodegeneration. The research was conducted by Dr. Silvia Mandel, Vice Director of the Eve Topf Center of Excellence for Neurodegenerative Diseases Research and Teaching, together with her colleagues Prof. Moussa Youdim (Technion), Prof. Judith Aharon (Rambam Medical Center), and Prof. Martin Rabey (Assaf HaRofeh Medical Center), as well as her colleagues from the Universities of Würzburg and Pisa.
"Currently, there is no blood test that can diagnose PD, making the detection of individuals at risk or at earliest stages of PD practically impossible. Instead it is identified by a clinical neurological examination based on findings suggestive of Parkinson’s disease. Finding biomarkers for Parkinson's disease will help to capture those high-risk subjects before symptoms develop, a stage where prevention treatment efforts might be expected to have their greatest impact to slow disease progression", says Dr. Silvia Mandel. "The first aim of our study was to assess whether a gene signature could be detected in blood from early Parkinson's disease patients that could support the diagnosis of the disease".
The examination was conducted on blood samples from 62 early stage Parkinson's disease patients and 64 healthy age-matched controls. The selection of the genes and determination of their expression in the blood was based on previous research conducted by Drs. Silvia Mandel and Moussa Youdim on the brains of Parkinson's disease patients, in which a group of genes was identified with defective expression compared to the brains of healthy people (control group). Five genes were found that are optimal predictors of Parkinson's disease.
The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stages of Parkinson's disease, with 100% accuracy, which suggests a potential for the genetic signature to assess disease severity. Lastly, the model fully discriminated between Parkinson's disease and Alzheimer's disease.
"The findings strengthen the assumption that a five-gene panel in the blood allows to diagnose early stage Parkinson's disease, with a possible diagnostic value for detection of the disease before the appearance of the characteristic motor symptoms", say the Technion researchers. "The biomarker could assist in diagnosing individuals at presymptomatic stages of the disease (patients with depression, sleep disturbances or hyposmia (reduced ability to smell) or patients carrying genetic risk factors) who are good candidates for neuroprotective treatment. Such a biomarker will be of value in clinical trials for the identification of that subgroup of Parkinson's disease patients that may respond favorably to therapies targeting the mechanisms reflected by the gene panel. All five genes play a role in the ubiquitin-proteasome system, whose involvement in the pathology of Parkinson's disease has previously been demonstrated.
The Technion researchers believe that, in the future, the blood test may be combined with brain imaging and/or biomarkers in the spinal fluid or other peripheral tissues, as a gold standard not only for early diagnosis, but also for the differential diagnosis of Parkinson's and motor disorders mimicking the disease.