Scientists at San Francisco-based KineMed, Inc., describe a new way to measure changes in the rates of deposition and breakdown of connective tissue applicable in animals and man. The methods described fill a critical need for better approaches to enable the discovery and development of drugs to treat a range of life-threatening diseases in which excessive deposition of collagen leading to organ dysfunction (fibrosis) plays a key role. Such advances can facilitate clinical trials for better treatments for such conditions as scleroderma, cirrhosis, pulmonary fibrosis and chronic transplant rejection.

Claire Emson, PhD, KineMed’s Lead Scientist in Fibrosis, presented KineMed’s new data in an invited talk entitled: “Measurement of Collagen Synthesis by Heavy Water Labeling and its Application for Identifying Anti-Fibrotic Therapies” at a Keystone symposium on Fibrotic Diseases, held in January 2009.

In KineMed’s new method, animals or humans drink heavy water, a safe, non-radioactive isotope of water. This heavy water serves as a building block for collagen newly synthesized during the period of observation. By then isolating collagen from small biopsies of the tissue of interest and using very sensitive and sophisticated mass spectroscopic analysis, rates of collagen synthesis or destruction can be measured precisely and rapidly – in days to weeks instead of the months to years previously required.

KineMed applied this new method to evaluate compounds as potential anti-fibrotic drugs and unexpectedly discovered significant anti-fibrotic activity of Noscapine, a drug originally used clinically as a cough suppressant. Noscapine substantially reduces fibrosis in several animal models of fibrosis in lung and liver. KineMed has patented the potential use of Noscapine in fibrotic disorders and is currently evaluating the activity of novel Noscapine-like analogues.

Fibrotic diseases are characterized by an accumulation of excessive collagen in tissues, in a process akin to exaggerated wound healing in response to tissue injury. Currently, there is a paucity of effective therapies to treat diseases characterized by fibrosis. One of the main impediments to bringing forward new treatments for fibrotic diseases has been difficulty in development.

Much of the difficulty comes from the variability in the extent and rates of progression of the diseases and the fact that organ dysfunction may take years to manifest after slow chronic deposition of collagen. As a result, clinical trials are long, very expensive and the potential benefits of drugs have been difficult to assess.

KineMed has pioneered a direct, more informative way to assess the extent and rate of progression of fibrosis, which measures the synthesis of collagen in vivo in both humans and animals. The Company believes that its proprietary method will address many of the challenges faced in bringing forward new drugs to treat the many patients with fibrotic diseases, for whom no effective treatments exist.

Marc Hellerstein, MD, PhD, KineMed’s scientific founder and professor at UCSF and UC Berkeley, observes, “We hope that KineMed’s novel method will speed the development of drugs to treat the large number of patients with diseases in which fibrosis plays a central role. The unexpected anti-fibrotic activity observed with Noscapine in animals encourages us to consider moving forward with clinical trials to more fully assess its potential. We are pleased by the interest that our findings have sparked in potential pharmaceutical partners.”

Source: KineMed, Inc.