Medical Device Daily Contributing Writer

Dr. Jay Lombard, a neurologist, is the co-founder and chief scientific officer of Genomind (Chalfont, Pennsylvania), a company focused on improving the lives of patients with psychiatric and neurological conditions through biomarker discovery. Lombard has researched and developed several novel therapeutic interventions to treat depression, dementia, and autism.

Prior to co-founding Genomind, he served as chief of neurology at Bronx Lebanon Hospital, and has held academic medical appointments at New York Presbyterian Hospital, Albert Einstein College of Medicine, and Touro College of Osteopathic Medicine.

MDD: The term "personalized medicine" is being used with increasing frequency, but it seems to have different meaning for different folks who use it. What is Genomind's definition of the term?

Lombard: You're right – personalized medicine has many different meanings to different people, but I think first and foremost is what it means to patients themselves. Patients do not want to be labeled with a diagnosis which often is arbitrary. Each person in a psychiatric setting brings a unique set of experiences and concerns, and personalized medicine means addressing these concerns rather than merely making a diagnosis and prescribing a particular drug based upon that diagnosis.

Where genetic biomarkers help in that regard is to really enlighten the clinician that this is not a one-size-fits-all patient encounter. If you look at prescribing habits for depression, and especially among primary care doctors, the lion's share of medications are selective serotonin-reuptake inhibitors (SSRIs). We know that with SSRIs, while effective for a significant percentage of patients with depression, there are almost as large a number of patients who either don't experience relief or who experience adverse drug effects. So a classic example of personalized medicine in psychiatry is that the use of SSRIs is not a one-size-fits-all; there are many different treatment options with unique sets of actions.

The second important point regarding personalized medicine in psychiatry is to dispel the notion that psychiatric disorders, whether it's depression, bipolar, schizophrenia, autism or even a cognitive disorder such as Alzheimer's disease, are not single disorders. They are biochemically heterogeneous with many different sub-endophenotypes. The implications of this is that not only are symptoms complex, but both the chemistry of these disorders and their treatment are unique as well.

MDD: What was the genesis of the Genecept Assay?

Lombard: The genesis of the assay is based upon an integrative matrix that provides genetic insights into all of the potential pathways related to brain function. These include an analysis of neurotransmitter pathways, neuroimmune pathways, pathways involved in sleep regulation and metabolism. In addition the assay includes an analysis of pharmacokinetics – how drugs are variably metabolized in the body.

For example, for the common co-morbidity of attention deficit disorder with depression, many depressive symptoms may resolve ASDD treatment is addressed, as opposed to treating depression as the primary problem. By the way, the reverse can also be as true sometimes. So the idea behind diagnostic markers in psychiatry and the origins of the Genecept assay is that psychiatric disorders are multi-dimensional and that the multi-dimensionality is driven by unique biological processes encoded by certain genetic variations.

For instance, in psychiatry, we know that psychiatric disorders for the most part are related to abnormalities in neurotransmitter signaling. Neurotransmitter signaling, such as serotonin, dopamine or glutamate, can either be elevated or depressed resulting in unique phenotypes and symptomatology, and we can actually relate these phenotypes to specific genetic variations and then couple these findings to specific neurotransmitter modulating drugs or medical foods.

Psychiatry is basically a trial-and-error process when trying to find the appropriate medication for an individual patient. One of the reasons Genomind was founded was the belief that we could create a new paradigm other than this trial-and-error process and this was ready to make its way into the clinic. My co-founder, Dr. Ronald Dozoretz, and I just felt the science behind this new paradigm is here now.

MDD: It appears to address the identification of a very large number of psychiatric conditions in a single assay, so I'm really wondering, how the heck does it do all that?

Lombard: It's an important question to ask, because the answer is that no psychiatric biomarker will ever be specific to a psychiatric disorder or be used exclusively for diagnostic purposes. The notion that we're going to discover a single gene in bipolar patients, for instance, will never happen because psychiatric disorders are not only multigenic, but have significant environmental influences that impact their causality as well.

The Genecept assay is not about diagnosing psychiatric conditions; it's really about understanding the biochemical basis of psychiatric symptomatology, with that symptomatology often overlapping in disorders which may look vastly different clinically.

A number of psychiatric disorders, such as bipolar, schizophrenia, autism and even treatment-resistant depression, may all display very similar biochemical variance and pathophysiologic mechanisms and yet have very different clinical manifestations.

This opens up, in my mind, an opportunity to shift our way of treating psychiatric patients away from a categorical diagnostic framework and treat these conditions in an etiologically specific manner. The hugest potential in using genetics in psychiatry is the help in getting us to the root cause of these disorders. I think this paradigm shift will greatly improve the therapeutic landscape in the near-term future.

MDD: Is there a simple way to phrase what the practitioner's goal is in using the Genecept assay?

Lombard: The simplest goals are to achieve faster remission rates, look for and understand that there exists alternative therapies which can either be pharmaceutical or medical food based and to avoid adverse drug effects. All three of these will help improve care, as we are already seeing today in real-world settings

(In Part 2 of this MDD Interview next week, Jay Lombard discusses some of the numbers that amount to a huge market for the Genecept assay, how the assay impacts the psychiatric treatment continuum, the regulatory and reimbursement paths for the company, and other areas being pursued by Genomind.)

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