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What is Collgard's focus? Collgard Biopharmaceuticals, the tissue therapeutics company, is developing a novel class of regenerative drugs designed to treat diseases at the tissue level. These drugs are intended to help restore tissue structure and function that were impaired or damaged following injury or continued stress. What is Tempostatin™ and how does it treat disease at the tissue level? Tempostatin™ is a small molecule that has been identified by Collgard as influencing a "master switch" in the tissue repair process. This process reflects interactions between the cells in a tissue and the protein support scaffold that binds the cells together - the extra-cellular matrix (ECM). In the setting of tissue injury or damage, Tempostatin™ acts as a potent and selective inhibitor of stromal cells activation, migration and proliferation and limits the excessive production of collagen type I, thereby preventing the expansion of the extra-cellular matrix. Thus, it exerts selective control of key elements in the common and fundamental process of tissue repair, offering great promise for treating a variety of diseases that share a common feature of progressive changes in tissue structure. What are stromal cells? Stromal cells are a family of connective tissue cells. These cells are involved in the production of extra-cellular matrix protein and in the maintenance of the mechanical and functional integrity of tissues and organs. What are collagens? Collagens are a closely related family of structural proteins that are essential for the assembly and maintenance of tissues and organs. In addition to providing mechanical strength, collagens play an important role in cell adhesion and migration. There are at least 19 types of collagens, collagen type I being the most prevalent, comprising up to 60-70% of the body's extra-cellular matrix protein. What diseases are candidates for therapy with Tempostatin™? There are two major classes of disease where gaining control of the tissue repair process may revolutionize therapy - fibrosuppression and cancer. In fibrosuppression, Tempostatin™ may improve the likelihood of tissue repair rather than replacement with a fibrotic scar. Clinically significant fibrotic disorders include:
In cancer, Tempostatin™ works in two ways - it suppresses the stromal support recruited by cancer cells, and it directly affects specific types of cancer cells. These two effects create a tremendous potential for using Tempostatin™ as part of cancer treatment, either as a monotherapy agent or in combination with other drugs. Tempostatin™ has specific promise in treating the following cancers:
Fibrosis is the end result of an uncontrolled activation of the tissue repair system. This system has two components, stromal cells and the protein scaffold - the extra-cellular matrix. Fibrosis occurs when tissue cells are over-stimulated, and rather than replace the normal components of a tissue, they instead generate a thickened and structurally simplified patch which is composed of excessive layers of collagen. The excessive amount of disorganized collagen, recognized as a scar, distorts and changes the tissue's structure. As organ function is exquisitely sensitive to tissue structure, tissue fibrosis is seen in almost all forms of organ failure, including liver, kidney and heart. Through its inhibitory effect on stromal cells and extra-cellular matrix protein synthesis, Tempostatin™ can exert its control on the tissue response, favoring repair. How is Tempostatin™ relevant to cancer? Cancer begins as a small, local collection of cells with abnormal growth properties. The disease becomes life threatening when cancer cells obtain the ability to invade local tissue and disseminate into remote areas of the body (metastasis). To survive and grow, cancer cells depend on stromal cells and on the stromal repair mechanism. Cancer cells exploit this mechanism to induce a stromal response that leads to the construction of new blood vessels (angiogenesis), providing tumors with a continuously replenished biological infrastructure they can employ to become generalized lethal diseases. By preventing the generation of tumor stroma, Tempostatin™ interferes with the interaction between tumor cells and stromal cells and deprive tumors of the biological infrastructure they need to grow and survive. Additionally, Tempostatin™ has a direct cytoreductive effect on a specific subset of tumors. Exposure of these tumor cells to Tempostatin™ results in programmed cell death (apoptosis). This subset of tumors includes gliomas, sarcomas, certain bladder carcinomas, and melanoma. How is Tempostatin™ relevant to heart disease? Abnormal tissue repair in the heart can happen in two different clinical situations. In the first situation, re-narrowing (restenosis) of blood vessels may follow treatment for blockage of the vessel. In at least 25% of the 600,000 patients that undergo coronary artery angioplasty in the United States each year, the treated vessels re-narrow within a few months of the procedure. This restenosis results from the migration and proliferation of smooth muscle cells (stromal cells) that produce excessive and undesirable amounts of collagen. Tempostatin™ arrests the activation of the arterial smooth muscle cells, suppressing their migration, proliferation, and undesirable collagen type I production. In the second situation, chronic volume overload of the heart may trigger a replacement of the normal extra-cellular matrix with a thickened scar-like collagen mass. This response to volume and pressure overload eventually replaces the normal tissue structure and severely limits the ability of the heart to function as a pump. In this condition, Tempostatin™ controls the activation of cardiac stromal cells, suppressing undesirable collagen type I production. Is Tempostatin™ safe for human use? Collgard has conducted monitored human clinical studies since 1998. The objective of these studies is to demonstrate that Tempostatin™ is safe and effective. In Phase I and Phase II clinical studies, Tempostatin™ oral tablets and dermal cream were found to be well tolerated in dosages that may in the future be shown to yield beneficial clinical effect. The company is currently entering expanded Phase II studies that will define an effective dose of the drug while carefully looking for any adverse effects. |