Anti-Meth Research Earns Student Award

By Jon Parham

 UAMS graduate student Shraddha Thakkar (center) was lead author on a paper detailing ongoing development of a meth addiction treatment by Kottayil I. Varughese, Ph.D., (left) and Eric Peterson, Ph.D.
UAMS graduate student Shraddha Thakkar (center) was lead author on a paper detailing ongoing development of a meth addiction treatment
by Kottayil I. Varughese, Ph.D., (left)
and Eric Peterson, Ph.D.

Thakkar, a doctoral candidate, was lead author of a paper about ongoing development of an antibody for treating methamphetamine addiction. The American Association of Pharmaceutical Scientists selected the paper “Design and In Vitro Testing of Structure-driven Mutations of an Anti-methamphetamine Therapeutic Single Chain Antibody with Subnanomolar Affinity” for an Innovation in Biotechnology research awards.

Thakkar presented the team’s research at the association’s May conference.

Just as the body’s immune system combats infections – this anti-meth antibody fragment could reduce the effects of the strongly addictive stimulant on the brain. Based on the structure of the antibody, Thakkar and the UAMS researchers examined different combinations of certain amino acids that make up the antibody to see which bonded best with a meth molecule. The team developed one combination that bonded several times more tightly than other versions, which could make it a more effective treatment.

“It’s fascinating to see the development of the antibody from the gene level and being able to design it then see how it will function,” said Thakkar, a student in the bioinformatics program offered jointly by the UAMS and the University of Arkansas at Little Rock. “You develop the structure of something that no one has seen before, then describe its function based on how it looks.”

The project is a collaboration by the labs of Eric Peterson, Ph.D., an assistant professor of pharmacology and toxicology, and Kottayil I. Varughese, Ph.D., a professor of physiology and biophysics.

Thakkar and the UAMS researchers examined how well these different combinations bonded best with a meth molecule. The combinations, in a crystal-like structure, were designed to generate tighter, or stronger, interactions between the two, which could lead to a more powerful addiction treatment.

“We were looking at the structure and the precise interactions that take place between the antibody and the meth molecule,” said Varughese, who is Thakkar’s faculty advisor. “Certain properties of each structure affected how well it bonded to the meth.”

The team developed one combination that bonded several times more tightly than other versions, which could make it a more effective treatment. The next step is continued testing of the most effective antibody structure.

“There is really no medication available to treat meth addiction,” Peterson said. “There are similar approaches for nicotine and cocaine addiction.”

The roots of creating antibodies as a possible tool against drug addiction come from the work of Michael Owens, Ph.D., professor and director of the UAMS Center for Drug and Alcohol Abuse, who holds the Wilbur Mills Endowed Chair in Alcohol and Drug Abuse Prevention.

Varughese credited Thakkar for helping move the meth research along. “An idea requires an enthusiastic student in order to move forward,” he said.

Thakkar, a native of India, looked at several schools for pursuing her doctorate. She said the close connection between the bioinformatics program and the College of Medicine was a big attraction to her and her research interests.

Co-authors of the research paper were Nisha Nanware-Kharade, Guillermo Gonzalez III, Brandon Linz, Jaya Nair, Reha Celikel, Varughese and Peterson.

The award was funded by Genentech.