Gene-to-drug

With the sequencing of the human genome, identifying approximately 25,000 genes, it has been made possible to predict new drug targets.  There are, however, few examples of developing drugs in this way.

Sclerostin antibody

The sclerostin antibody project arose from the "gene-to-drug" approach and evolved from the study of a rare inherited disease found predominantly in an Afrikaner population in South Africa, called sclerosteosis. The affected individuals have very high bone density and notably strong bones, whilst suffering from few clinical issues connected with excessive bone deposition. Studies on the sclerosteosis patients suggested that the high bone mineral density was due to increased bone formation rates rather than a major suppression of bone resorption. It was recognised that a controlled increase in bone formation rates could be desirable in patients suffering from low bone mineral density disorders such as osteoporosis, where bone loss puts patients at increased risk of bone fracture. Most current therapeutic approaches focus on reducing bone loss; the potential to stimulate the formation of new high quality bone in patients with low bone mineral density represents a novel approach to bone loss disorders.

Genetic mapping and extensive genomic sequencing allowed the identification of the mutation in sclerosteosis patients that resulted in their high bone mass phenotype. The mutation inactivates an osteocyte-produced protein called sclerostin that plays an important role in negatively regulating the anabolic output from the osteoblasts, the cells responsible for building bone (or for stimulating bone formation). UCB in collaboration with Amgen have shown that administration of the sclerostin antibody can result in a controlled increase in bone formation and bone strength in several different species.