Future Challenges

Bone diseases are an exciting research focus at the Merck Frosst Centre for Therapeutic Research, with possible applications in arthritis and other collagen diseases as well as osteoporosis.

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Bone is a dynamic, responsive tissue that is being constantly recycled and remodelled by two cell types with opposing activity: osteoblasts form bone tissue and osteoclasts resorb it. One research project at the Centre for Therapeutic Research is targetting cathepsin K, a key proteolytic enzyme involved in the digestion of the collagen matrix of bone by osteoclasts. The aim is to block the resorption of bone and thereby increase bone mass in diseases such as osteoporosis, in which the bone becomes thin and fragile.

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Blockade of cathepsin K is an obvious target for a "bone-building" therapy. People who lack cathepsin K naturally through a rare genetic deficiency have bones that are too heavy and dense-a disease called osteopetrosis or marble bone disease. The inference from these patients is that, while it is not desirable to block cathepsin K function throughout the lifetime of an individual, it might be desirable to inhibit this enzyme in patients suffering from osteoporosis. Scientists at the Centre for Therapeutic Research are involved in a multi-site project to develop a potent, selective and safe inhibitor of cathepsin K, by collaborating with colleagues in the Merck & Co., Inc. bone biology group at West Point, Pennsylvania and a Californian biotech company, Cetera Genomics.