Deadenylase enzymes as potential novel drug targets in osteoporosis, bone disease, and repair

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In the UK, women over 45 years old spend more time in hospital due to osteoporosis than heart disease, diabetes or breast cancer. Common hip, wrist, and spinal bone fractures due to decreased bone density are a huge financial cost to the NHS and impact significantly on morbidity and the quality of life, in particular of women and the elderly. Although several options are available for the prevention and treatment of osteoporosis, currently available drugs are not always effective. Moreover, not all patients tolerate the available medications due to side-effects. If successful, our project is the first step towards novel drugs of the future that may be useful for the treatment of osteoporosis, bone disease and repair. These future drugs will have more desirable characteristics compared to current medications. They will be available as tablets, have fewer side-effects and enhance bone formation directly by stimulating bone-forming cells. The idea behind the selection of the enzyme target in bone-forming cells comes from genetically engineered mice with heavy bones and studying the relevant enzymes in great detail. We will search for drug-like molecules by screening a large collection of thousands of compounds using robots. In parallel, we will use high-performance computer clusters to screen a database with information of up to 1 million compounds using ?cheminformatics?. We will then optimise our hits using synthetic chemistry and test the activity of our compounds by looking at bone formation in cell culture dishes. If successful, our research will identify molecules that may represent candidates for future drug development.