Novel Treatments for Kidney Diseases and Ovarian Cancer Therapy

A look into two of Innovation's Discovery Grant Profiles.

Novel Treatments for Kidney Diseases Joseph Bonventre, MD, PhD BWH, RENAL Acute Kidney Injury is characterized by a rapid decline in kidney function and can be triggered by a number of insults. While AKI may resolve on its own or with care, the sequelae can include Chronic Kidney Disease (CKD), end stage renal disease and death. Kidney Injury Molecule – 1 (KIM-1) is a cell membrane glycoprotein that functions as a receptor for cellular degradation products to enable clearance of these products from renal tubules in response to injury enabling recovery of renal function. The laboratories of Benjamin Humphreys, MD, PhD and Joseph Bonventre, MD, PhD at BWH have collaborated to show that sustained expression of KIM-1 is associated with chronic renal inflammation and fibrosis leading to kidney failure. Dr. Bonventre's laboratory has been engaged in research on KIM-1 for several years producing several important results. These include elucidating the molecular biology of KIM-1 along with its homeostatic and pathological roles. Recent epidemiological research suggests AKI may play a much stronger role in the incidence of kidney failure, the eight leading cause of death in the U.S. than previously thought. Ovarian Cancer Therapy Patricia Donahoe, MD MGH, Surgery, Pediatric Surgical Research Ovarian cancer and onco-fertility are just two of the significant unmet needs that may be addressed through therapy with Müllerian-inhibiting substance (MIS, also known as anti- Müllerian substance). About 14 thousand women will die from ovarian cancer in the United States this year whereas cytotoxic therapies in young women often lead to infertility. Groundbreaking studies by Patricia Donahoe, MD (MGH Surgery) showed that MIS inhibits growth of human ovarian cancer cell lines and targets cancer progenitor populations. MIS based replacement therapy prevent the irreversible loss of ovarian reserve, by restoring fertility upon cessation of cytotoxic cycles. MIS is a large glycoprotein normally made by the body during development to specifically kill certain reproductive cells. The Donahoe group has generated new proprietary MIS cDNA constructs for large scale expression of homogeneous and biologically active MIS. The IDG allowed the group to ramp up production of the protein drug up to 100mg and to establish a new process to reproducibly express and purify the drug with increased quantity, quality and potency.