GDNF mimetics project includes animal experiments. Animal use in the later stages of the project is necessary to demonstrate the activity of GDNF mimetics in vivo in the rat model of Parkinson disease. PD is a devastating movement disorder, and thus new medications should improve clinical manifestation of the disease. It is thus not possible to evaluate the efficiency of developed molecules for PD therapy in in vitro systems. Only animal models could provide a satisfactory estimate of activity of GDNF mimetics and are accepted by EMA and FDA.
Animal experiments will be performed in accordance with the regulations of European Union (European Directive 2010/63/EU regulations for animals used in the research) and State of Finland (The Act on Animal Experimentation, Decree on Animal Experimentation, Animal Welfare Act). For all experiments involving animals the permission from the Committee for Animal Experiments of the University of Helsinki and the chief veterinarian of the County Administrative Board will be obtained.
Experimental design will be guided by the 3Rs (refinement, reduction and replacement) principles.
To comply with the refinement principle animals will be housed in safe, clean, well-lit and appropriate in any way environment. All housing procedures and experimental procedures will be performed by experienced professionals and guided by European and Finnish legislation. Appropriate anesthesia will be used during surgery procedures.
To comply with the reduction principle the number of experimental animal will be kept as low as possible. It willl be calculated using Russel Lenths’s software (Lenth, 2006-9; Lenth, 2007) to achieve the statistical power in the experiment equal to 0.8. In addition, multiple biological readouts (behavioural, immunohistochemical, biochemical data) will be followed from in the same animals. To reduce the number of animals used for preparation of primary cultures of dopaminergic neurons, we optimized conventional method to obtain higher throughput (Planken et al., 2010) allowing analysis of multiple data point from one mouse.
To fullfill the replacement principle whenever possible we will use in silico experiments and cell cultures to test developed compounds.