Investigating the genetics of Parkinson’s disease

Learning from a patient population 30% more likely to develop PD

By Jesse Cedarbaum, M.D.
Vice President, Early Clinical Development

June 26, 2017

Parkinson’s disease (PD) is a complex condition, often caused by a combination of genetic and environmental influences. Yet in the last decade, a few genes have been identified that single-handedly contribute to the disease. The discovery of these genes and their direct link with PD may act as a strong catalyst for the development of new treatments.  Two of these genes, glucocerebrosidase (GBA) and LRRK2, are so called founder mutations that can be traced back to a small group of ancestor patients. Genetic mutations often gradually disappear from a population over time, but they can be preserved in genetically conserved populations.

A founder population
Over the last 10 years, Drs. Nir Giladi and Avi Orr-Utreger and their teams at Sourasky Medical Center of Tel Aviv University in Israel, have uncovered much about the genetic basis of PD. Their research established the high prevalence of monogenic forms of the disease in the Ashkenazi Jewish population in Israel. Throughout history, the Ashkenazi Jewish population has experienced several periods of drastic population decline and re-emergence. This has amplified certain surviving genes, which account for a number of monogenic diseases common in this specific population. As it turns out, approximately one-third of PD patients in the Ashkenazi Jewish population carry a mutation in the GBA or LRRK2 genes. Understanding specific causes of PD in this patient population may unlock faster, cost-efficient methods to diagnose, monitor and treat the disease.

16 million dollars, 5 years
To capitalize on this knowledge and expertise, in late 2016 Biogen finalized a five-year, $16 million agreement with the Tel Aviv researchers. This collaboration, which will support research into investigating a drug for the treatment of familial PD, is the result of more than a year’s work for our Parkinson’s Disease Program Team, led by Jesse Cedarbaum, with support from Alfred Sandrock, Chief Medical Officer. Biogen participants in the collaboration are drawn from all corners of the company, including the Neurodegeneration & Repair Unit in Research and Early Development (RED), Global Clinical Operations (GCO), Global Biomarker Discovery & Development (GBDD), Genetics & Computational Biology, R&D IT, and Biostatistics.

What we hope to discover about PD
As of June 2017, the project has enrolled its first 145 participants, and aspires to recruit up to 800 individuals, including patients with PD, patients at-risk for the disease, family members and healthy controls. It is anticipated that data will be generated using clinical assessment, genetic analysis, and brain imaging, with follow up for up to five years. Our hope is that the collaboration will elucidate important aspects of PD, including the identification of other genetic and epigenetic factors that affect the disease development in at-risk patients; the validation of biomarkers of disease progression, such as imaging methods, cerebrospinal fluid biomarkers, and wearable biosensors to monitor patients. Interestingly, carriers of the mutations without PD may also be an ideal population for studying the underlying pathogenesis of the disease and to advance neuroprotective strategies for those with PD.

The Biogen-Tel Aviv agreement represents a new large-scale, collaborative approach to dissecting the genetics that lie behind PD, regardless of ancestry.

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