URI pharmacy professor awarded $1.65 million to study alcoholism treatment with NIH colleague

1 of only 9 teams nationally to receive funding

KINGSTON, R.I. – December 3, 2013 – A University of Rhode Island pharmacy professor has been awarded a $1.65 million National Institutes of Health grant to study a new treatment for alcoholism.

The grant awarded to Fatemeh Akhlaghi, URI professor of biomedical and pharmaceutical sciences, formalizes a partnership with Dr. Lorenzo Leggio, chief of Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology at the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse, and Pfizer, the world’s largest research-based pharmaceutical company.

Akhlaghi’s group was one of only nine teams in the United States to win such an award from NIH. This collaborative pilot initiative, called Discovering New Therapeutic Uses for Existing Molecules, is led by the National Center for Advancing Translational Sciences (NCATS) and funded by the NIH Common Fund. The two scientists are working with an undisclosed compound provided by Pfizer, which has been used to treat Type II diabetes.

A central target of their research is ghrelin, an aminoacid peptide that stimulates appetite and food intake. In those with alcoholism, higher ghrelin concentrations are associated with higher alcohol craving and consumption, according to the researchers.

An oral medication that targets the activity of ghrelin and can pass through the blood-brain barrier holds promise for treatment, according to their grant proposal.

“If we can stop food cravings, then maybe we can stop alcohol cravings. Simply put, URI is helping NIH develop a new treatment for alcoholism,” said Akhlaghi, whose previous work has focused on diabetes and anti-rejection drugs taken by transplant patients. Her expertise is in the area of drug development.

The researchers are examining whether a ghrelin receptor inhibitor safely reduces alcohol dependence. The work follows promising human and animal tests, which showed ghrelin blocking activity.

Akhlaghi has been working with Leggio since he was a researcher at Brown University, Providence. In 2012, the two collaborated on the grant application under the NIH’s drug repurposing program, which awarded a total of $12.7 nationally in 2013.

Leggio sought Akhlagi out for this latest project because of her expertise in pharmacokintetics, which studies a medicine’s effects on the body, and pharmacodynamics, which focuses on how the biological processes in the body affect medication.

The two are following up on Leggio’s study at Brown, during which he infused study subjects with ghrelin. In each case, alcohol craving went up.

“I am looking at timing, the course of the drug in the body, the drug concentration and how all of those relate to a drug’s effectiveness,” Akhlaghi said. “Right now, we don’t know anything about a suitable drug regimen for this compound, so we need to measure concentration and effect. We need to know how long the drug must stay in the body to do its job.”

Now she is analyzing samples from Leggio’s NIH lab to look at concentration and effectiveness markers.

The research team is first looking at the safety of this drug combined with alcohol. The next potential step will be to look at early signals of efficacy, including using functional magnetic resonance imaging (fMRI) to determine whether the craving signal in the brain is dampened if ghrelin is inhibited.

“In a sense, we are saying, if we can change your brain, we can change your life,” Akhlaghi said. “