Animal models human disorders

Alini M et al (2008) Are animal models useful for studying human disc disorders/degenera-tion Eur Spine J 17(1) 2—19... 

The human leukodystrophies are inherited disorders of central nervous system white matter. These disorders are characterized by a diffuse deficiency of myelin caused by a variety of genetic lesions and often manifest before 10 years of age (Table 38-1). Some are caused by mutations in the PLP gene and resemble the PLP animal mutants described in Chapter 4 [ 1,23]. As with the animal models, depending on the nature of the mutation, they vary from a severe form in connatal Pelizaeus-Merzbacher disease (PMD) through an intermediate phenotype in classical PMD to a mild phenotype in spastic paraplegia. It is noteworthy that some mutations of the PLP gene also cause a peripheral neuropathy [24], very probably related to the expression of low levels of PLP in peripheral nerve (see Ch. 4). 

There are three generally accepted criteria for validating animal models for human psychiatric disorders face validity, construct validity, and predictive validity. Face validity refers to the outward appearance of the model, i.e. does the animal s behavior adequately reflect the human behavior being modeled In this dimension, anxiety models have a clear advantage over other psychiatric models it is usually quite apparent if an animal is frightened, whereas it is a much more difficult to assess whether an animal is displaying psychotic-like or depressive-like behavior, for example. 

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

The website continues, "The use of animal models to study neuro-developmental disorders has also been expanding, particularly here at UC Davis, which has schools of medicine and veterinary medieine, as well as a primate research center. Monkeys and other nonhuman primates have brains organized comparable to humans, making them ideal research models for the study of neuro-developmental disorders."... 

It shows significant activity against a spectmm of neurodegenerative disorders in animal models that replicate many of the features of important human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson s disease [147]. 

Myriad Genetics reports that Flurizan is a selective amyloid-lowering agent (SALA) that reduces levels of the peptide amyloid beta 43 in cultured human cells and in animal models. Results of a completed Phase II follow-on study of Flurizan in patients with mild AD were presented in July 2006 at the International Conference on Alzheimer s Disease and Related Disorders. According to Myriad Genetics, results from this study reportedly... 

The above project represents a novel approach and a possible new treatment for psychiatric disorder. The possibility that neuronal discharge short of total brain convulsion may have psychiatric effects would be a major advance in understanding the action of ECT. Moreover, a possible substitute treatment for ECT would be a major clinical breakthrough. TMS might allow us to stimulate deep brain regions without convulsions, pain, or known hazards. Before one widens the use of TMS in humans, further evaluation of the effectiveness of TMS in animal models for depression is necessary. Our hypothesis is that ECT exerts its therapeutic effects by stimulation of specific brain regions. We suggest that TMS may exert therapeutic effects without need for total brain convulsion. 

This brief overview highlights some of the more promising peptide-based relationships to the anxiety disorders from the more than 50 neuropeptides identified. Investigations into the role of peptides in human states of anxiety have included localization, animal modeling, postmortem receptor assays. 

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