Targeted Secretion Inhibition: Applications in Oncology, Endocrinology, and Neurology/Pain
Offered by Harvard Catalyst's Reactor Program, this pilot funding opportunity provided up to $50,000 in funding plus access to Ipsen's Targeted Secretion Inhibitor (TSI) technology platform to expand the clinical potential for this novel class of biopharmaceuticals.
This pilot grant opportunity promoted the design, development, and evaluation of novel TSIs for their potential clinical application in cancer, endocrine, neurological disorders, or pain. A critical feature of this research program is Ipsen's commitment to provide any awardees, who may require it, with scientific and technical support to design and develop project-related TSIs. Successful applicants did not necessarily need to be able to generate the TSI molecular constructs for their proposed work.
TSIs are based on the structure and function of botulinum neurotoxins which are comprised of two peptide chains linked via a disulfide bond. The light chain (LC) possesses a proteolytic activity that can disrupt vesicle function and the associated secretion process. The heavy chain (HC) contains two domains, a transmembrane domain responsible for membrane insertion and translocation of the LC and a targeting domain responsible for binding to the motor neuron by the parent molecule. Botulinum neurotoxin stops secretion of vesicle components by its targeted proteolytic activity. Replacement of the neurotoxin targeting domain with another protein sequence (receptor, mAb, hormone, etc.) directs the recombinant secretion inhibitor to any desired cell type where it can disrupt normal secretion processes.
TSIs can inhibit cellular secretion for prolonged periods and may be suitable for use in a wide range of diseases where inhibition of cellular secretion could provide new therapeutic potential.
Pilot grant proposals described innovative and translational research projects that, if successful, could provide new insights into the application of TSI technologies to inform: (1) clinical decisions; (2) disease detection, causation, progression, or treatment; or (3) the development of new therapeutics, diagnostics, or clinically informative biomarkers. Proposals should focus on applications in the fields of oncology, endocrinology, or neurology/pain.
Five pilot grants were awarded in amounts of up to $50,000 for each one-year project - starting February 1, 2018