European Drug Development Project Targets Gram-negative Bacteria

A consortium of European universities, research institutes, and biopharmaceutical companies has been established to discover and develop novel new antibiotics, especially for treatment of gram-negative bacterial infections.

The ENABLE (European Gram-Negative Antibacterial Engine) project brings together more than 30 European universities and companies, in a six-year program funded by the Innovative Medicines Initiative (Brussels, Belgium), a joint undertaking between the European Union and the pharmaceutical industry association EFPIA (European Federation of Pharmaceutical Industries and Associations – Brussels, Belgium).

The ENABLE project, which is the third within the ND4BB (New Drugs for Bad Bugs) series, spans 13 countries and charges the 32 partners with the mission of establishing a significant antibacterial drug discovery platform for the progression of research programs through discovery and Phase 1 clinical trials.

The primary target of the ENABLE project is gram-negative bacteria. Medically relevant gram-negative bacilli include a multitude of species. Some of them cause primarily respiratory problems (Hemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa), primarily urinary problems (Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens), and primarily gastrointestinal problems (Helicobacter pylori, Salmonella enteritidis, Salmonella typhi).

One of the several unique characteristics of these bacteria is the structure of the outer membrane. The outer leaflet of the membrane comprises a complex lipopolysaccharide (LPS) whose lipid portion acts as an endotoxin. If LPS enters the circulatory system, it causes a toxic reaction, with the sufferer developing a high temperature, high respiration rate, and low blood pressure. This may lead to endotoxic shock, which can be fatal. This outer membrane protects the bacteria from several antibiotics, dyes, and detergents that would normally damage either the inner membrane or the cell wall's (peptidoglycan). The outer membrane provides these bacteria with resistance to antibacterial agents such as lysozyme and penicillin.

MEDINA (Granada, Spain), one of the participants in the ENABLE project, is an independent nonprofit research and development organization established jointly by the pharmaceutical company Merck Sharp and Dohme, the government of Andalucia, and the University of Granada. Its researchers are actively seeking new molecules from its proprietary natural product libraries to develop new medicines that respond to unmet medical needs.

“MEDINA brings to the project one of the novel antibiotic molecules that will be developed within this partnership. Our participation in this program represents a fantastic opportunity to jointly develop one of our most advanced compounds in our pipeline,” said Dr. Olga Genilloud, scientific director of MEDINA. “MEDINA offers a unique and longstanding expertise in drug discovery. We are committed with the global research effort for the discovery of new antibiotics, as continuity of a long history of success which has resulted in some of the most important breakthrough drugs available to patients today.”

Related Links:
Innovative Medicines Initiative
European Federation of Pharmaceutical Industries and Associations
MEDINA