The UHN study team, co-led by Dr. Toshiyuki Araki, Assistant Scientist, Campbell Family Institute and Dr. Peter Backx, Senior Scientist, Toronto General Research Institute and the Peter Munk Cardiac Centre, and Professor of Medicine, Division of Cardiology and Department of Physiology, U of T, investigated Noonan Syndrome. The Boston team, led by Dr. Maria Kontaridis, Assistant Professor of Medicine Harvard Medical School and Division of Cardiology, BIDMC, investigated LEOPARD Syndrome.
The scientists introduced the genetic mutations that cause these syndromes into special strains of mice, and were able to reproduce the features of the human disorders. The Toronto group found that "excessive activity of an enzyme called ERK, a downstream target of the RAS pathway, caused HCM in Noonan Syndrome, and successfully used a drug that lowers the activity of this enzyme to decrease pathway activity and normalize all of the features of Noonan Syndrome," says Dr. Neel. The Boston group found that LEOPARD Syndrome results from excessive activity of a different enzyme downstream of RAS, called mTOR. Using the mTOR inhibitor Rapamycin, which is already approved as an immunosuppressant, they were able to reverse HCM in their mouse model of LEOPARD Syndrome.
"These research findings are important steps towards understanding the pathogenesis of these congenital syndromes, and point the way toward clinical trials of these agents in severely affe
|Contact: Jane Finlayson|
University Health Network