This consortium grant is a competitive renewal of a previous award to Markou, in collaboration with Novartis, when her laboratory was located at Scripps Research. Chemists at Novartis involved in the previous phase of the program discovered a number of small-molecule modulators of the GABAB receptor. Further study resulted in the development of the first highly selective positive modulators for GABAB receptors. Subsequently, work in the Markou laboratory showed that these compounds had desirable effects on nicotine dependence in animal models, while offering a better side-effect profile than other alternatives under study (full agonists at the same receptors).
"As a result, a strong preclinical proof-of-concept has already been established for this novel approach to the treatment of nicotine addiction that drives the harmful tobacco smoking habit," Markou said. "The preclinical results in our animal models are really exciting and have provided the momentum for me to continue on this project, even after Novartis indicated that it no longer wished to maintain this collaboration."
Markou reached out to her Scripps Research colleagues and formed a new research team to continue work on the initiative. "I am very fortunate to have such outstanding collaborators who are cutting-edge chemists and have extensive experience in drug discovery," she said. "After the neurobiological studies pointed out the important role of the GABAB receptor in nicotine reward, and we had positive data in a variety of animal models of nicotine dependence, it was time to focus our efforts on discovery of new molecules that could become therapeutics to assist people to quit smoking."
The new funding will advance this effort.
Griffin noted, "We want to expand the pipeline of possible compounds that could be developed into potential therapies. Once we have a better mechanistic understanding of the factors that drive selective modula
|Contact: Mika Ono|
Scripps Research Institute