Montreal – As the precursor of a drug which may one day provide effective treatment for the common and very serious problem of preterm birth, PDC113.824 may have a very exciting future, despite its dry name. “We are excited about this compound because it belongs to a new class of drug, and because it has potential to prevent premature labour, possibly with fewer side effects than current treatments,” says Dr. Stephane Laporte, researcher in endocrinology at the Research Institute of the McGill University Health Centre (RI-MUHC) and corresponding author of a recent study of PDC113.824 that was published in collaboration with Université de Montreal (UdeM) and other Quebec research centres, in the Journal of Biological Chemistry.
“At the moment little is known about how preterm birth can be prevented and although clinical interventions have focused on inhibiting uterine contraction there is no consensus on treatments for premature labour,” adds Dr. Sylvain Chemtob, a professor of the Faculty of Medicine at UdeM and researcher at the Research Centre of the CHU Sainte-Justine. “The drugs available today are ineffective and can have side effects for mother and unborn child. Development of this compound is especially significant because it has a different, more targeted mode of action than conventional pharmaceuticals, and therefore may cause fewer side effects.”
An effective treatment to reduce the risk of preterm birth is urgently needed. According to the Society of Obstetricians and Gynaecologists of Canada, premature labour is one of the most common problems in pregnancy and the cause of 75 per cent of all newborn deaths in babies without birth defects.
Compound PDC113.824 is one of an emerging class of pharmaceuticals known as biased allosteric drugs. This class of drugs interacts with receptors on the cell’s surface in a different way than conventional drugs, and produces different effects. “Think of the cell as a model train set,” explains Dr. Laporte, who is also an associate professor of medicine at McGill University. “In this analogy, conventional drugs make the train speed up or slow down. Allosteric biased drugs, on the other hand, while they can change the speed of the train, may actually also switch the train to a different track.”
The compound studied by Dr. Laporte and his colleagues from UdeM not only acts on different cell receptors than those usually targeted in the uterus, but can modify the cell’s usual response to stimulation by natural substances – a property known as “bias.” Neither allosteric drugs nor biased drugs are completely new, but there are very few examples of compounds, which have both these properties.
This class of drugs is of great interest to pharmaceutical companies as they offer the potential for new therapeutic agents with increased efficacy and selectivity. A few such drugs are already in use.
About the study
The study, a collaborative effort by researchers from the Research Institute of the MUHC, McGill University, Université de Montreal and Centre Hospitalier Universitaire Sainte-Justine Research Center, was conducted on laboratory mice. It was funded by a Canadian Institutes of Health (CIHR) Research Team Grant in GPCR Allosteric Regulation.
About the McGill University Health Centre (MUHC) One of the world’s foremost academic health centres, the MUHC offers exceptional and integrated patient-centric care, research and teaching. Highly committed to the continuum of care in its community and affiliated with the Faculty of Medicine of McGill University, The Montreal Children’s Hospital, the Montreal General Hospital, the Royal Victoria Hospital, the Montreal Neurological Hospital, the Montreal Chest Institute and the Lachine Hospital of the MUHC value multidisciplinary service throughout the lifespan, innovative technologies and practices, strategic partnerships and leadership in knowledge transfer. The MUHC is currently carrying out a $2.25-billion Redevelopment Project on three campuses—the Mountain, the Glen and Lachine—designed to provide healthcare professionals with an effective environment in which to ensure patients and their families benefit from The Best Care for Life. The campuses are also anchored in best sustainable-development practices, including LEED® and BOMA BESt guidelines.
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Research is organized by eleven research axes (or programs). Located in Montreal, Quebec, Canada, the Institute is the research arm of the McGill University Health Centre affiliated with the Faculty of Medicine at McGill University. The Institute supports over 600 researchers, 1,000 graduate students, post-docs and fellows devoted to a broad spectrum of fundamental and clinical research. Over 1000 clinical research studies are conducted within our hospitals each year. The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec (FRSQ).
About McGill University
McGill University, founded in Montreal, Que., in 1821, is Canada’s leading post-secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 35,000 students. McGill attracts students from more than 150 countries around the world. Almost half of McGill students claim a first language other than English – including 6,200 francophones – with more than 6,800 international students making up almost 20 per cent of the student body.
About the Université de Montréal
Deeply rooted in Montreal and dedicated to its international mission, the Université de Montréal is one of the top universities in the French-speaking world. Founded in 1878, the Université de Montréal today has 16 faculties and together with its two affiliated schools, HEC Montréal and École Polytechnique, constitutes the largest centre of higher education and research in Québec, the second largest in Canada, and one of the major centres in North America. It brings together 2,500 professors and researchers, accommodates more than 56,000 students, offers some 650 programs at all academic levels, and awards about 3,000 masters and doctorate diplomas each year.