CNS/Neurological Disease Models

Southern Research offers the following well-developed CNS/neurodegenerative disease models for use in the continuum of CNS drug development, ranging from proof-of-concept studies and optimization of lead candidates to preclinical toxicity and efficacy evaluations.

Animal Model of Amyotrophic Lateral Sclerosis (ALS). Southern Research utilizes G93A mice, a classical model for SOD-1 abnormality, to assess the efficacy of compounds for ALS. This model is based on the evaluation of three parameters: weight loss due to muscle atrophy; neurological scores in the classical 4 grade scale; and ability to right. The symptoms of the disease usually develop around day 105, and the animals reach a neurological score of 4 around day 125-130 when they become unable to right and feed. Compounds can be administered around the projected time of onset, and animals are monitored for extension of life expectancy, improvement of neurological scores, and maintenance of the righting reflex.

Parkinson's Disease Efficacy Model. Parkinson's disease (PD) is the second most frequently occurring neurodegenerative disease today. While the neuropathology of PD involves a number of different neurotransmitter pathways, the nigrostriatal dopaminergic pathway is one that is severely affected by this disease. This pathway is studied using a dopamine neurotoxin-induced mouse model, the MPTP (methyl-4-phenyl-1,2,5,6-tetrahydropyridine) model. The MPTP Parkinson's Disease Mouse Model has been validated and is currently in use at Southern Research. In our laboratory, we have obtained a greater than 70% decrease in dopamine and dopamine metabolites measured in the brain striatum, as compared to a saline control group, while maintaining stable catecholamine levels during the study. Additionally, we have achieved significant losses of dopaminergic neurons via histochemical visualization. This model can be used to evaluate compounds for prophylactic and/or therapeutic use. Using a standard study design, we have the capability to determine the efficacy of multiple compounds at several dose levels with common control groups. In this design, comparisons can be made between compounds and between different doses or formulations of the same compound from the biogenic amine assay and unbiased stereology.

Glioma Model. Subcutaneously implanted skin xenografts of glioblastoma-dervied cells are available to assess the overall effect of agents on the growth of glioblastomas and target modulation. Brain implants of glioblastoma cells can also be used to determine the effect of possible therapeutics on the growth of tumors in the brain.