"IGF-I in the treatment of cerebellar ataxia: experimental models and project for a clinical assay"

I. Torres Aleman. Cajal Institute. Madrid.

IGF-I is a wide-spectrum neurotrophic factor of probable physiological importance in the maintenance of nerve function. In our laboratory we have been testing its therapeutical potential in a number of neurodegenerative diseases, most prominently on animal models of cerebellar ataxia. We have shown that systemic administration of IGF-I to ataxic rats results in a complete reversal of functional impairment. Permanent functional recovery, as assessed in a rota-rod test is obtained even if IGF-I is administered to animals with pronnounced neuronal depletion. In alternative models of hereditary cerebellar ataxia (the Purkinje cell degeneration mouse) chronic subcutaneous administration of IGF-I results in normalization of motor coordination rates in moderately ataxic mice and in substantial recovery and over 100% increase in life-span in mice severely affected. These resultssupport the use of IGF-I in the treatment of cerebellar degeneration in humans. We are currently designing in collaboration with clinical neurologists a type II clinical trial with a limited number of patients using an "open-study" paradigm. Patients in the first stages of the disease will receive daily subcutaneous injections of IGF-I for 2 years. Periodical evaluation of clinical outcome will be conducted with the newly published scale for ataxia symptons.