Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal cerebellar cell suspensions, prepared from wild-type (+/+) mice, were implanted bilaterally into the cerebellum of Purkinje cell degeneration' (pcd) mutant mice, a model of adult-onset recessively inherited cerebellar ataxia, to study the functional effects of the grafts on motor coordination and fatigue resistance in a rotating rod treadmill paradigm. The viability of transplanted Purkinje cells was verified with immunocytochemistry for calbindin-D28k and for glutamate receptor 2/3 subunits and with in situ hybridisation histochemistry for insulin-like growth factor I mRNA, biochemical markers normally expressed by Purkinje cells in the cerebellum. Sham injections of vehicle did not appreciably modify the performance of pcd mutants in the rota-rod tests. On the other hand, bilateral cerebellar grafts led to a 3.5-fold increase in the time period that recipient pcd mice were able to stay on the rotating drum based on the comparison of mean scores (of three trials) or a 5.5-fold increase based on the comparison of maximum scores (of the three trials). These findings provide evidence for a motor enhancement in the pcd mouse model of hereditary cerebellar ataxia following intracerebellar transplantation of primordial Purkinje cells.
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PMID:Graft-induced restoration of function in hereditary cerebellar ataxia. 854 77

We tested the potential of insulin-like growth factor I (IGF-I) to induce functional recovery in an animal model of cerebellar ataxia because this motor impairment is accompanied in humans and rodents by distinct changes in several components of the IGF-I trophic system. Rats rendered ataxic by deafferentation of the cerebellar cortex with 3-acetylpyridine recovered motor function after IGF-I was administered, as determined by behavioral and electrophysiological tests. When treated with IGF-I, inferior olive neurons, the targets of the neurotoxin, were rescued to various degrees (from 92 to 27% of surviving neurons), depending on the time that treatment with IGF-I was initiated. Furthermore, full recovery was obtained regardless of the route by which the trophic factor was administered (intraventricular or subcutaneous) even in rats with severe neuronal loss. These results suggest that human ataxia could be treated with IGF-I by a simple procedure.
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PMID:Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia. 944 18

In the present work we review evidence supporting the use of insulin-like growth factor I (IGF-I) for treatment of cerebellar ataxia, a heterogeneous group of neurodegenerative diseases of low incidence but high societal impact. Most types of ataxia display not only motor discoordination, but also additional neurological problems including peripheral nerve dysfunctions. Therefore, a feasible therapy should combine different strategies aimed to correct the various disturbances specific for each type of ataxia. For cerebellar deficits, and most probably also for other types of brain deficits, the use of a wide-spectrum neuroprotective factor such as IGF-I may prove beneficial. Intriguingly, both ataxic animals as well as human patients show altered serum IGF-I levels. While the pathogenic significance of IGF-I, if any, in this varied group of diseases is difficult to envisage, disrupted IGF-I neuroprotective signaling may constitute a common stage in the pathological cascade associated to neuronal death. Indeed, treatment with IGF-I has proven effective in animal models of ataxia. Based on this pre-clinical evidence we propose that IGF-I should be tested in clinical trials of cerebellar ataxia in those cases where either serum IGF-I deficiency (as in primary cerebellar atrophy) or loss of sensitivity to IGF-I (as in ataxia telangiectasia) has been reported. Taking advantage of the widely protective and anabolic actions of IGF-I on peripheral tissues, this neurotrophic factor may provide additional therapeutic advantages for many of the disturbances commonly associated to ataxia such as cardiopathy, muscle wasting, or immune dysfunction.
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PMID:Insulin-like growth factor I treatment for cerebellar ataxia: addressing a common pathway in the pathological cascade? 1595 Feb 89