In some ways, there has been very little change in the neurodegenerative landscape since the turn of the century. For example, in 2000, there were four approved drugs for Alzheimer’s Disease: Cognex; Aricep; Excelon; and Razadyne. Eleven years later, the same four drugs are still the only FDA-approved drugs for AD. These drugs only provide short and temporary improvement in symptoms and there are no drugs that reverse progression. In the last couple of years, a number of high-profile clinical trials have also failed in phase III clinical trials, including the Dimebon, Rosiglitazone, Bapineuzumab and Solanezumab trials. These failed clinical trials, coupled with the ongoing difficulty in achieving quick results within the neurodegenerative field (e.g., Dimebon), have contributed to the pharmaceutical industry’s increased risk aversion, and have resulted in industry’s requiring the existence of compelling target validation before investing in and/or initiating new drug discovery projects. Consequently, early stage drug discovery research in neurodegeneration has been abandoned or has seen massive cut backs and/or changes in the strategies used by the pharmaceutical industry.
The LDDN was established to discover chemical tools from which a new generation of drugs to treat neurodegenerative diseases could be developed. Since then, the LDDN has succeeded in helping to transform discoveries in the basic biology of neurodegeneration into opportunities for drug discovery. Each drug discovery program at the LDDN begins when a principal investigator approaches the LDDN about initiating a collaboration based upon the discoveries in neurodegenerative diseases in his/her laboratory. When such a partnership arises, the LDDN’s contribution is the discovery and optimization of molecules that can be used as tools for both basic research and as lead structures in the discovery and development of new therapeutics.