BPS 2015
Development of a vectorised neurotensin for therapeutic hypothermia
Jamal Temsamani
Director of Drug Development, Vect Horus
ABSTRACT
Therapeutic hypothermia is currently warranted in many pathological situations: resuscitation after cardiac arrest (or before surgical procedures that involve stopping the heart), severe traumatic brain injury, cerebral ischemia, neonatal/hypoxia/ischemia. Physical approaches for reducing body temperature have been employed (e.g., cooling blankets, infusion of cold fluids, etc.). These physical approaches, however, are difficult to implement, expensive, may have delayed onset and may induce undesirable side effects such as shivering.
Neurotensin (NT) is a linear tridecapeptide which is mainly expressed in the CNS. When administered directly into the brain, NT exerts a potent hypothermia effect. However, clinical use of pharmacological, NT-induced, hypothermia is hampered by a very rapid proteolytic cleavage in plasma upon systemic administration. Moreover its poor blood brain barrier (BBB) permeability hampers its therapeutic potential.
Vect-Horus has developed a technology to improve the brain uptake of various molecules using peptides vectors. Coupling neurotensin with a peptide vector resulted in a significant enhancement of stability, affinity and brain uptake. Furthermore, the vectorised neurotensin induced a hypothermic effect which was maintained for several hours, while free neurotensin failed to do so. This long-duration effect is of great interest since a long-term hypothermia is essential to treat patients following cardiac arrest. Effects on neuroprotection in animals correlated well with hypothermia induction.
The compound is currently in regulatory preclinical phase and Phase 1 studies are scheduled early next year.
BIO
Dr. Jamal Temsamani has over 20 years’ experience in the management of R&D and the development of academic partnerships and research collaborations with the pharmaceutical industry. He joins Vect-Horus in October 2014 after several years of experience in the field of drug delivery using peptide vectors.
Dr. Temsamani obtained his Ph.D. in molecular biology from the University of Montpellier. After completing a post-doctoral fellowship at the Worcester Foundation For Experimental Biology (MA, USA), he joined the company IDERA Pharmaceuticals (MA, USA), where he served as Associate-Director and then as Director of the Discovery group. He then held several positions including as Vice President of R&D at Synt:em (Nimes) and CLL Pharma (Nice). He has a strong scientific expertise in the field of pharmacology and preclinical development. He has published more than 60 scientific articles and is co-inventor of 40 patents.