Team Receives High RO1 Scores
A research laboratory in the Department of Anesthesia, Critical Care and Pain Medicine received an exceptionally high score in the top 3 percent from the National Institutes of Health (NIH) on its RO1 grant application.
The team, led by Dr. Douglas Raines, is working with etomidate, a commonly used anesthetic, to create new drugs that could potentially decrease or eliminate side effects in patients.
The RO1 grant, or Research Project Grant, is "the original and historically oldest grant mechanism used by NIH," according to the NIH website. RO1 grants are the major NIH mechanism for individuals to get NIH funding, Dr. Raines said.
Etomidate is useful because, unlike other anesthetics, it doesn't cause a drop in blood pressure, according to Dr. Raines.
However, etomidate suppresses the ability of the adrenal gland to make certain steroids.
"These steroids are critical for life, particularly in patients who are critically ill," Dr. Raines said.
To counteract the steroid inhibition problem, the team pursued two solutions. In one project, the lab added a metabolically labile ester group to etomidate to create a new, short-acting drug that is rapidly metabolized by the body, Dr. Raines said.
"It's a strategy that's been employed before, but not for an anesthetic like etomidate," he said.
In the second project, the team created an etomidate analogue called carboetomidate, Dr. Raines said. Carboetomidate induces anesthesia and maintains stability, but doesn't inhibit the adrenal gland.
"By making a change in a single atom in etomidate, we were able to reduce the potency for inhibiting [the gland] by about a thousandfold," Dr. Raines said.
The findings on the first drug will be published in the journal Anesthesiology, which issued a press release with the American Society of Anesthesiology. In addition, the team has applied for patents for these drugs and related analogues.
The NIH will notify the group in October about whether it will receive funding, he said.
Dr. Raines thanked the other members of the team, including Drs. Joe Cotten, Stuart Forman, Keith Miller and Shaukat Husain. He also thanked the DACC, the Partners Center for Drug Discovery (Drs. Joydev Laha and Greg Cuny), and the NIH for their support.
Pictured: Dr. Douglas Raines gives a lecture on new etomidate analogues at a CIMIT forum on June 24, 2008.
ASA press release
Mass General press release
Dr. Douglas Raines faculty profile
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