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Targeted Secretion Inhibition: Applications in Oncology, Endocrinology, and Neurology/Pain
Offered by Harvard Catalyst’s Translational Innovator, 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. 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.
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 was 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.
Pilot grant proposals described innovative and translational research projects that, if successful, could provide new insights into the application of TSI technologies to inform:
- Clinical decisions
- Disease detection, causation, progression, or treatment
- 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
Principal Investigator: Cyril Benes, PhD. Massachusetts General Hospital
Tyrosine kinase inhibitors (TKIs) have become the standard of care for many cancer types that have specific genetic alterations. This includes non-small cell lung cancer (NSCLC) patients with EGFR mutations and in general the response to EGFR TKI is good. However, drug resistance can emerge and limit the clinical benefit. A large collection of patient-derived fibroblast (PDFs) that has been built by the lab will be used to decipher the function of PDFs in the development of therapeutic resistance. Targeting the tumor fibroblast’s secretion of growth factors using Ipsen’s innovative targeted secretion inhibition (TSI) approach could represent a new method to counter drug resistance in NSCLC.
Principal Investigator: Giada Bianchi, MD. Dana Farber Cancer Institute
Multiple myeloma (MM) and AL amyloidosis (AL) are diseases of clonal plasma cell (PC) proliferation and hyper-secretion of monoclonal immunoglobulin (paraprotein). MM is the second most frequent blood cancer in the western world, with a peak incidence in the 7th decade of life. AL is a rare, rapidly fatal disorder characterized by deposition of amyloid in target organs, leading to failure and eventually death.
Botulinum toxin (BoNT) has proven effective in reducing paraprotein secretion in plasma cell proliferation. This project will test a proof of concept of chimeric BoNT that will target the paraprotein in MM/AL. The ultimate goal would be the use of chimeric BoNT for patients with MM/AL and/or other paraprotein related disorders.
Principal Investigator: Michael Mannstadt, MD. Massachusetts General Hospital
The purpose of the proposal is to explore the suitability of the Targeted Secretion Inhibitor (TSI) platform as a novel treatment of hyperparathyroidism. Primary hyperparathyroidism is a common endocrine disorder caused by overproduction of parathyroid hormone (PTH) from the parathyroid glands. Recent trends in the US suggest that the incidence of the disease is >100,000 new cases annually, predominantly affecting post-menopausal women. This project will explore the potential of the TSI platform to inhibit PTH secretion.
Principal Investigator: Taru Muranen, PhD. Beth Israel Deaconess Medical Center
The overarching goal of these studies is to uncover mechanisms by which secreted stromal proteins promote drug resistance in pancreatic cancer and to develop strategies to inhibit these mechanisms. Pancreatic ductal adenocarcinoma is one of the most lethal and drug resistant of all cancers.
This project proposes to identify ways to selectively inhibit secretion by pancreatic stellate cells in order to improve therapy outcomes in pancreatic cancer. Through the use of the TSI platform this project will develop treatment strategies to block secretion by the pancreatic stellate cells and test their efficacy in our model systems.
Principal Investigator: Paul Rosenberg MD PhD. Boston Children’s Hospital
Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured, and soon begin to die. The question that will be addressed in this project is whether a botulinum toxin based strategy can be used to block Zn2+ secretion from retinal amacrine cells following optic nerve injury and effectively promote axonal regeneration and neuronal survival.