Emerging strategies for drug development in motor neuron disease

Until recently, attempts to identify disease-modifying treatments in motor neuron disease have largely failed. This was due to a lack of understanding of the disease pathogenesis and poor clinical trial design. Recent advances in the genetics of motor neuron disease and the maturation of tissue culture techniques have increased our understanding of the mechanisms of cell death in motor neuron disease. This has in turn led to better in vitro and transgenic animal models, allowing for a more systematic study of the disease process and analysis of potential therapeutic agents. With the advent of these models, motor neuron disease drug research has entered a new era. It is now possible to pursue mass screening of compounds in the in vitro models. Successful compounds in vitro can be advanced to the transgenic animal models. Once toxicity and potential therapeutic effects in animals are known, agents which remain promising can be taken to Phase I, II and III clinical trials. This will increase the likelihood of success and is more desirable than methods previously utilised. A hierarchical approach such as this will be even more important as multi-drug regimens are to be studied. The number of combinations for these multi-drug regimens becomes prohibitive without a screening method.