TDO Inhibitors: A New Treatment Option for Parkinson’s Disease

Study Rationale:                   
Tryptophan-2,3-dioxygenase (TDO) is a key enzyme in the tryptophan degradation pathway. In a Parkinson’s disease (PD) model, TDO was identified as a potential therapeutic target. Scientists at the Netherlands Translational Research Center (NTRC) have developed an innovative TDO screening assay (laboratory experiment) and have applied this assay to identify inhibitor compounds. NTRC will improve the potency and properties of these compounds.

Hypothesis:
Potent inhibitors of TDO can be used as tools to validate TDO inhibition as a viable treatment option for PD.

Study Design:
NTRC has screened nearly 400,000 compounds for their TDO inhibitory activity and has identified several compounds that are attractive starting points for optimization. Researchers will synthesize a variety of closely related compounds in order to identify a clear relationship between the structure of the compound and its TDO inhibitory activity. Establishing this relationship is a vital step to further improve the potency of the compound series and to optimize the compounds to enable them to be efficiently absorbed and distributed.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
Studies in pre-clinical models have indicated that TDO inhibition might alter the course of PD progression. When sufficiently translated to humans with PD, TDO inhibition could provide a novel disease-modifying therapy.

Next Steps for Development:
Once a compound fulfills our criteria it will be tested in a pharmacokinetic study. High and stable compound levels are important for a compound to be effective in pre-clinical models and, ultimately, in PD patients.