The data produced comparing optimal doses to the SNc of MANF = 10 ug and GDNF = 10 ug in this model indicate the following at four weeks post-treatment:
- MANF reduced behavioral deficits by 53%, whereas behavioral deficits with GDNF increased by 20%;
- MANF produced a 14.4% reinnervation of the striatum, whereas striatum innervation with GDNF was reduced by 9.9%;
- MANF increased dopamine concentrations in the striatum, whereas striatum dopamine concentrations with GDNF did not increase.
"We are excited about our results with MANF as we have demonstrated superiority to GDNF in a number of key areas related to recovery of function in Parkinson's disease," added Dr. Joseph Rubinfeld, Amarantus advisor and Amgen Co-Founder. "We intend to continue to move our Parkinson's program forward, while also evaluating other disease indications for MANF with potentially accelerated regulatory pathways, including certain orphan diseases. This strategy may significantly reduce MANF's overall time to market versus a Parkinson's-only strategy."
In the study, rodents were lesioned with 6-OHDA on one side of their brain (t = 0). Behavior was tested for baseline (t =1 week) and vehicle, MANF (3 ug, 10 ug or 36 ug) and GDNF (10ug) were injected in different groups of animals at t = 2 weeks. Behavior was tested for drug effect at t = 4 weeks (2 weeks post-treatment) and at t = 6 weeks (4 weeks post-treatment).
The behavioral data achieved statistical significance with a p value of less than 0.03 with animal groups of N=12. The striatum reinnervation data and dopamine concentration data did not achieve statistical significance because the animals sacrificed from the behavioral study were divided into 2 separate groups of N=6 for the analysis of densitometry (striatum reinnervation) and neurochemistry (dopamine concentration in the striatum). The method of analysis of the rat brains did not allow for the densitometry and neurochemistry to be analyzed simultaneously in the same animals, leading to groups of N = 6 or less, which was insufficient to achieve statistical significant.