Population Diagnostics, Inc (PDx), a private company with a novel approach to revealing the genetic causes of disease and predicting drug response, has been awarded a federal grant to identify the genetic causes of Parkinson’s Disease. Funded by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health, the project is being led by Eli Hatchwell, an associate professor at Stony Brook University Medical Center and a co-founder of PDx.

“Parkinson’s Disease is a heterogeneous disorder, meaning that it is actually many diseases masquerading as one general set of symptoms,” said Jim Chinitz, Population Diagnostics’ chief executive. “Historically, Parkinson’s patients have been lumped together as a diagnosis based on clinical observations, but there may actually be dozens of subtypes of Parkinson’s that can be delineated as genetic subgroups. This grant will allow us to systematically reveal the genes that harbor disease-causing mutations for Parkinson’s Disease.”

Breakthroughs in the genetic and therapeutic research fields of Parkinson’s Disease have been stymied because the search for its genetic causes have mistakenly relied on the predication that this disease is mainly caused by “common” genetic variants (the “Common Disease / Common Variant” hypothesis). This theory meant that a common set of mutations would cause Parkinson’s and in aggregate explain why the Parkinson’s patient population may experience symptoms differently (for example, age of onset, severity, etc.). Genomic scientists are now beginning to acknowledge that the Common Disease / Common Variant hypothesis and the related methodology behind discovering common variants is flawed.

In contrast, Population Diagnostics’ gene discovery platform stems from the company’s understanding that common complex diseases, such as Parkinson’s Disease, will ultimately be classified by a collection of rare variants within multiple genes. Each rare variant will be capable of independently causing the common set of symptoms that currently define a Parkinson’s diagnosis. Population Diagnostics has developed its patented gene discovery methods based on the Common Disease / Rare Variant hypothesis. Recent discoveries of rare causative variants that have a severe effect in other common diseases such as autism and schizophrenia, support Population Diagnostics’ strategy.

“A rational therapeutic approach to Parkinson’s Disease will remain elusive until more genetic subgroups of PD can be clearly delineated and validated,” said Dr David Tegay, a clinical geneticist, and Parkinson’s Disease clinician who is a consultant to this project. “While known genes associated with PD such as SNCA and LRRK2 are medically relevant, they only permit genetic subtyping in fewer than 10 percent of PD patients. I am confident that Population Diagnostics’ novel biomarker discovery platform will be the key that rapidly unlocks the door to the missing heritability of this debilitating disease.”

Dr Eli Hatchwell added, “Our approach to revealing causative, rare variants will result in the identification of multiple genes that affect different biological pathways. Thus, each mutation may cause the clinical symptoms of Parkinson’s Disease. It isn’t surprising that traditional therapeutics research has been disappointing, given that a particular drug molecule design is unlikely to be effective in more than one relevant pathway at a time. In the future, when a comprehensive set of causative rare variants collectively explain a far greater percentage of Parkinson’s patients, rational therapeutic development strategies targeted toward the correct pathways can be effectively applied. This exemplifies the promise of personalized medicine, the field in which Population Diagnostics is at the forefront.”

Jim Chinitz further commented, “I encourage other Parkinson’s Disease stakeholders such as foundations and pharmaceutical companies to take note of what Population Diagnostics is doing differently, and consider the Common Disease / Rare Variant discovery method that we have pioneered and are scaling up. Through partnering relationships, we know that associating genetic subtypes to targeted therapeutics will be greatly accelerated.”

Population Diagnostics is applying its discoveries in human genetics to the development of DNA-based diagnostics and personalized medicine tests.