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In the army now
LEXINGTON, Mass.—Since signing a $1 billion deal with GlaxoSmithKline PLC (GSK) in the summer of 2009 to create deuterium-modified versions of GSK pipeline compounds, Concert Pharmaceuticals Inc. has been working to narrow the broad therapeutic area potential of its deuterium chemistry approach to a more focused set of diseases. One of those areas selected by Concert is central nervous system diseases, and more particularly, neurological disorders. That new focus has garnered Concert its next big deal, a Cooperative Research and Development Agreement (CRADA) with the Walter Reed Army Institute of Research (WRAIR) to conduct preclinical testing on a novel compound derived from Concert's deuterated chemical entity (DCE) platform for seizure protection associated with traumatic brain injury (TBI).
According to Concert, its DCE platform has the potential to have a lot of applications across a variety of small-molecule therapeutics. A non-radioactive relative of hydrogen that can be isolated from sea water, deuterium is heavier than hydrogen, forming a stronger chemical bond to a carbon atom of a molecule. This bond obtained by selective deuterium modification may substantially improve the drug's metabolic properties, potentially resulting in better safety, tolerability and/or efficacy of an isotope of hydrogen.
Now that the company has narrowed the focus of potential applications of the DCE platform, Concert and WRAIR are going in search of drug compounds that have demonstrated anti-seizure activity in preclinical models and may be effective in the treatment of various epileptic or seizure-generating diseases and injuries, such as ischemic stroke and traumatic brain injury (TBI).
"We're focusing on areas such as seizure, pain and other specialty neurological indications where we think the specific compounds we have discovered using the DCE platform provide real advantages over anything that is commercially available," says Dr. Roger Tung, president and CEO of Concert. "There is growing recognition within the industry and the public about the need for treatment of these indications in addition to brain trauma and seizure—areas that are certainly topical from a variety of perspectives."
TBI, in particular, is a major public health problem, occurring at a rate of over 1.4 million injuries per year in the United States, according to the Centers for Disease Control. It is of specific concern for military personnel deployed to Iraq or Afghanistan. According to the U.S. Department of Defense, approximately 200,000 cases of TBI have been diagnosed in military service members over the past decade.
WRAIR's laboratory conducts basic and applied research aimed at the mechanisms and pathophysiology of brain injury, with a specific focus on developing improved diagnostics and novel neuroprotective therapeutics. Dr. Frank Tortella, who will conduct the studies for this CRADA in his lab and who serves as chief of the Brain Trauma Neuroprotection and Neuroplasticity Branch in the Center of Excellence for Military Psychiatry and Neuroscience at the WRAIR, said in a statement announcing the CRADA that brain injuries are a major area of interest to WRAIR.
Under the terms of the CRADA, announced Feb. 2, Concert and WRAIR will share costs on the preclinical efficacy evaluation of the novel drug compound developed using Concert's DCE platform. The WRAIR will perform testing of Concert's compound using its relevant preclinical model of brain injury and lend its expertise in evaluating the compound's potential for treatment of brain diseases and injury.
The compound, explains Tung, is a deuterium-modified version of a compound "discovered years ago in an academic lab," for which Tung adds, "there was never an impetus to take that compound to the market, even though it showed pretty interesting effects in animal models of epilepsy."
Tung is not able to disclose any other specific details about the compound, but adds: "It has a novel mechanism for standard epileptic seizure use, but we are also intuiting that it may be useful for a newly recognized form of epilepsy that doesn't result in seizures, but instead internal damage within the brain which is believed to be the cause of some serious trauma."
"This is something you see a lot of in armed forces personnel, so Walter Reed was very interested in understanding its mechanism and finding potential treatments," Tung adds. "When we approached them with our version of it, which is a more stable version, they were very interested and pushed us to the front of the line in terms of possibly having a CRADA."
This "broke some groundspeed records in terms of entering into that CRADA," Tung says, and notes, "they agreed to share costs with us, which is not normal procedure."
Concert is also collaborating with the National Institute of Neurological Disorders and Stroke's (NINDS) Anticonvulsant Screening Program to evaluate anti-seizure activity in a series of deuterium-modified compounds. This government-sponsored effort at NINDS is focused on preclinical testing of active drug compounds, through a series of in-vivo and in-vitro models, to define their potential as antiepileptic drugs.