Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain insulin-like growth factor I (IGF-I) and its related molecules may be involved in neurodegenerative processes in which IGF-I-containing pathways are compromised. Since IGF-I is present in the olivocerebellar circuitry, two types of late-onset cerebellar ataxias (olivopontocerebellar and idiopathic cerebellar cortical atrophy) were chosen to test this hypothesis. The following significant changes in the peripheral IGF-I system of these patients were found: low IGF-I levels, and high IGF-binding protein 1 (BP-1), and BP-3 affinity for IGF-1. Sixty percent of the patients also had significantly low insulin levels. Patients suffering from other neurological diseases with cerebellar dysfunction and ataxia not involving the olivocerebellar pathway also had low IGF-I levels, while IGFBPs and insulin levels were normal. Our data indicate that degeneration of an IGF-I-containing neuronal pathway produces significant changes in the peripheral IGF system. This suggests strongly that the endocrine (bloodborne) and the paracrine/autocrine (brain) IGF systems are linked functionally. We propose that alterations in the blood IGF-I system may constitute a marker of some cerebellar diseases.
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PMID:The insulin-like growth factor I system in cerebellar degeneration. 860 52

We compared some biobehavioral effects of ethanol in transgenic mice that overexpress insulin-like growth factor I (IGF-I) in brain and in those that exhibit ectopic: brain expression of IGF binding protein I with those in non-transgenic littermate controls. Ethanol-induced sleep in IGF-I transgenic mice was significantly shorter, and in IGF binding protein 1 transgenic mice significantly longer, than in controls. A similar tendency, though not significant, was observed for ethanol-induced hypothermia. The groups did not differ in the degree of ethanol-induced ataxia. IGF-I transgenic mice did not acquire tolerance to either the hypothermic or hypnotic effects of ethanol following 7-day ethanol treatment. In contrast, tolerance in IGF binding protein 1 transgenic mice was significantly more pronounced than in controls. There were no significant differences among the three groups in the peak blood alcohol concentrations or the overall blood alcohol curves following acute ethanol challenge. In general, these data support the prediction made that chronically elevated exposure to IGF-I in IGF-I transgenic mice renders them less susceptible to the effects of ethanol than their non-transgenic siblings, and that overexpression of IGF binding protein 1 has the opposite effect.
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PMID:Insulin-like growth factor I expression alters acute sensitivity and tolerance to ethanol in transgenic mice. 881 32

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

The therapeutic potential of peptide growth factors as insulin-like growth factor I (IGF-I) is currently under intense scrutiny in a wide variety of diseases, including neurodegenerative illnesses. A new poly(lactic-co-glycolide)-based microsphere IGF-I controlled release formulation for subcutaneous (SC) delivery has been developed by a triple emulsion method. The resulting microspheres displayed a mean diameter of 1.5microm, with an encapsulation efficiency of 74.3%. The protein retained integrity after the microencapsulation process as evaluated by circular dichroism and SDS-PAGE. The administration of IGF-I in microspheres caused at least a 30-fold increase in IGF-I mean residence time in rats and mice when compared with the conventional SC solution. Therefore, dosing can be changed from the conventional twice a day to once every 2 weeks. Therapeutic efficacy of this new formulation has been studied in mutant mice with inherited Purkinje cell degeneration (PCD). These mice show a chronic limb discoordination that is resolved after continuous systemic delivery of IGF-I. Normal motor coordination was maintained as long as IGF-I microsphere therapy is continued. Moreover, severely affected PCD mice, with marked ataxia, muscle wasting and shortened life-span showed a significant improvement after continuous IGF-I microsphere therapy as determined by enhanced motor coordination, marked weight gain and extended survival. This new formulation can be considered of great therapeutic promise for some chronic brain diseases.
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PMID:Microspheres containing insulin-like growth factor I for treatment of chronic neurodegeneration. 1460 9

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

Inherited neurodegenerative diseases such as Friedreich's ataxia (FRDA), produced by deficiency of the mitochondrial chaperone frataxin (Fxn), shows specific neurological deficits involving different subset of neurons even though deficiency of Fxn is ubiquitous. Because astrocytes are involved in neurodegeneration, we analyzed whether they are also affected by frataxin deficiency and contribute to the disease. We also tested whether insulin-like growth factor I (IGF-I), that has proven effective in increasing frataxin levels both in neurons and in astrocytes, also exerts in vivo protective actions. Using the GFAP promoter expressed by multipotential stem cells during development and mostly by astrocytes in the adult, we ablated Fxn in a time-dependent manner in mice (FGKO mice) and found severe ataxia and early death when Fxn was eliminated during development, but not when deleted in the adult. Analysis of underlying mechanisms revealed that Fxn deficiency elicited growth and survival impairments in developing cerebellar astrocytes, whereas forebrain astrocytes grew normally. A similar time-dependent effect of frataxin deficiency in astrocytes was observed in a fly model. In addition, treatment of FGKO mice with IGF-I improved their motor performance, reduced cerebellar atrophy, and increased survival. These observations indicate that a greater vulnerability of developing cerebellar astrocytes to Fxn deficiency may contribute to cerebellar deficits in this inherited disease. Our data also confirm a therapeutic benefit of IGF-I in early FRDA deficiency.
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PMID:A role for astrocytes in cerebellar deficits in frataxin deficiency: Protection by insulin-like growth factor I. 2828 93