Objective/Rationale:
The objective of this project is to assess the effects of oral administration of Cogane™ (PYM50028) in reversing the changes in the brain involved in Parkinson’s disease (PD) and the associated movement disability using two pre-clinical models. In addition, this project will establish the therapeutic dose levels and duration of treatment that provide these benefits in these models to gain essential information on the appropriate dosing and design for a Phase II clinical study in Parkinson’s disease patients.
Project Description:
In the first study, Cogane™ will be administered orally every day for up to two months in an established pre-clinical model of PD. Beneficial effects will be assessed by taking measurements of biochemical markers specific for the disease. The second study will use a more complex pre-clinical model of PD. A range of doses of Cogane™ will be administered orally every day for up to four weeks, and the levels of Cogane™ in the body will be measured. The third study using the same model will utilize the optimal dose of Cogane™, determined from the previous study, administered orally every day for up to 26 weeks. Beneficial effects will be assessed by taking measurements of biochemical markers and recording the movement disability characteristic of the disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The body naturally produces proteins known as neurotrophic factors that stimulate the growth of nerves. In particular, one known as GDNF has been shown to re-grow damaged nerves in areas of the brain involved in PD. Injection of GDNF in the brain showed beneficial effects in a small clinical study. Cogane™, which can be taken orally, stimulates the body to release GDNF and therefore has the potential to overcome many of the surgical difficulties associated with GDNF administration.
Anticipated Outcome:
This project will provide evidence on the ability of Cogane™ to reverse the changes in the area of the brain involved in PD and the associated movement disability using pre-clinical models. In addition, this project will provide essential information on the appropriate dosing and design for a Phase II clinical study to assess the potential benefits of orally administered Cogane™ in PD patients.
Final Outcome
Cogane™ has been shown to be not only neuroprotective but also neurorestorative in a pre-clinical model of PD. In another model more closely mimicing human PD it was demonstrated that once daily oral administration of Cogane™ for 18 weeks significantly reduced the median parkinsonian disability by 43 percent and that this reduction was still increasing after 18 weeks. In conclusion, the neurorestorative efficacy of Cogane™ is associated with plasma levels >400 ng/ml and brain levels >4000 ng/g and the plasma level associated with efficacy can be reached by once daily oral dosing in PD patients.
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