Neuroscience Expert: Challenges Ahead, But “Research Bandwidth” Can Expand

People pose for photo

Guest lecturer Dennis Choi, MD, PhD, right, with Fredy J. Revilla, MD, Director of the Gardner Center at UCNI. Dr. Choi was Dr. Revilla’s mentor and department chairman at Washington University in St. Louis about a decade ago. Photo by Cindy Starr / Mayfield Clinic.

The esteemed neuroscientist Dennis Choi, MD, PhD, special guest lecturer at the University of Cincinnati (UC) College of Medicine, on Thursday issued a warning about funding for neuroscience drug research and expressed his hope for a new model of collaboration involving the National Institutes of Health, academic health centers like UC, and the pharmaceutical industry. He called for “increased bandwidth” in the number of ideas that can be converted into active research, and he said that foundations can play a more proactive role in disease philanthropy.

The Harvard-educated Dr. Choi, who took a leave from his faculty position at Emory University to serve as Executive Vice President of the Simons Foundation, is uniquely positioned to make such far-reaching pronouncements. He has held leading neurology posts at Washington University in St. Louis and Emory University in Atlanta, and he served as Executive Vice-President of Neurosciences at the Merck Research Lab from 2001 to 2006. The Simons Foundation, based in New York City, supports a significant initiative in autism research known as SFARI.

Speaking to a roomful of clinicians and researchers, many of them affiliated with the UC Gardner Neuroscience Institute, Dr. Choi described the complexities involved in knowing whether a drug will be effective. Will the body absorb it? Will it hit the target without causing cancer? Spending more time and money understanding the biological and molecular infrastructure of a disease, he said, might help researchers zero in on therapies that are likely to be successful.

He noted that the cost to industry of launching a new drug in 2004 was $1.78 billion, a staggering amount that can cause tension between the needs of society and the demands of shareholders. Dr. Choi witnessed firsthand the costly, time-consuming process of working potential drugs forward at Merck, where, he said, people joked that “a standard unit of chemists” was 20 chemists.

As global investment in drug discovery has soared and productivity has diminished, he said, Wall Street has taken notice, and pharmaceutical stock prices have sagged. “If you had sold one of your shares of Pfizer and bought Apple a couple of years later,” he said, “your stake in Apple would be worth nearly $15,000.”

“What’s of particular concern,” he continued, “is that neuroscience is taking it on the chin. “There is a major failure scenario, and the way you know that is several companies have closed their neuroscience efforts. So this is actually a crisis. If society is allowed to stop developing therapeutics for nervous system diseases, it is an ominous step for the future of mankind.”

Dr. Choi described the current situation as “a failure of the free-market system” that is nevertheless entirely solvable by changing regulatory rules so that the business case for investment is improved.

Dr. Choi also put forward a new research model. In today’s “linear model,” he said, where NIH and foundations fund basic research at academic institutions and discoveries are then passed to industry to develop drugs and test them in clinical trials, “the bandwidth is maxed out, and I fear that at our current pace we’re leaving all kinds of good ideas on the table.”

The only way to increase “the bandwidth of exploration” in a time of limited resources, he said, is to change to an integrated, multidirectional model in which both funding agencies and academic medical centers join industry in driving clinical exploratory testing. As an example he pointed to the study of progesterone as a possible medical treatment following traumatic brain injury. The study originated in Emory’s department of emergency medicine, where researchers had long talked about the promise of progesterone. Without government or corporate funding, the researchers decided, “Let’s just test it ourselves.”

The small pilot study supported the hypothesis that progesterone reduced mortality, and today the National Institute of Neurological Disorders and Stroke, a division of NIH, is funding a national, multi-site study of progesterone known as ProTECT III. UC Health / University Hospital is a study site, with efforts led by Jay Johannigman, MD, Professor and Director of the Division of Trauma and Critical Care, and Lori Shutter, MD, Professor of Neurosurgery and Neurology and Director of the Neurocritical Care Program.

Foundations, likewise, can play an important role, Dr. Choi said. “Instead of sitting passively in the background solely funding investigator-initiated research projects, more and more foundations are stepping forward into more proactive roles, and so you see more and more of them blur the line between their scope of operations and those of biotechnology companies. It was my fascination with this sector’s progressive engagement that caused me to take my leave of absence from Emory and work with the Simons Foundation.”

— Cindy Starr 

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