As the enzyme striatal-enriched phosphatase (STEP) may be abnormally elevated in aged parkinsonian pre-clinical models with cognitive deficits, the possibility exists that STEP inhibition could significantly reduce these cognitive impairments. This initial study will examine the pharmacokinetic profile of a STEP inhibitor drug as a potential precursor to efficacy studies.
This study will examine absorption and distribution of the STEP inhibitor TC-2153 and demonstrate activity following oral administration to pre-clinical models.
In the first part of the study, different doses of the drug will be given orally and blood samples will be taken at various times after drug administration to measure drug and metabolite levels. A similar study will be performed using intravenous administration of drug for comparative purposes.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
If successful, STEP inhibitors may continue toward clinical application for cognitive decline seen in Parkinson’s disease.
Next Steps for Development:
Depending on the outcomes, additional studies may be performed in which the STEP inhibitor TC-2153 is administered to aged models with Parkinson-like cognitive deficits to examine the extent to which it can improve cognitive functioning.
This pilot study has shown the bioavailability of the novel Striatal-Enriched Phosphatase (STEP) inhibitor TC-2153 in blood following intravenous and oral administration in preclinical models. This pilot study has also demonstrated that by taking blood samples from aged preclinical models following oral administration of TC-2153 and applying these samples to a STEP inhibition assay, inhibition of STEP protein can be observed, demonstrating that TC-2153 (and potentially active metabolites) is not only present in plasma following oral administration in monkeys but is biologically active. This data, in conjunction with preliminary data demonstrating the ability of TC-2153 to improve cognitive deficits, and the presence of increased STEP protein expression in other PD preclinical models support the need for further study to assess the effects of STEP inhibition with TC-2153 on cognitive function.