Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protirelin (thyrotropin-releasing hormone) appears to be a neuromodulator in the extrahypothalamic nervous system and has been suggested as an adjunct in the treatment of amyotrophic lateral sclerosis (ALS). Clinical studies have been divided on the efficacy of protirelin (TRH) despite strong experimental findings that are consistent with a role for the peptide in ALS. Recent findings provide evidence of a gender-related specificity in the ability of protirelin to potentiate the monosynaptic reflex. While castration in male neonatal rats lowered the sensitivity to protirelin, testosterone treatment restored that sensitivity. An examination of the clinical studies reveals a failure either to identify patients' sex or to separate the results on the basis of sex. These findings provide convincing evidence for the potential efficacy of protirelin in ALS if the patient's sex and underlying hormonal status are taken into account.
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PMID:Protirelin (thyrotropin-releasing hormone) in amyotrophic lateral sclerosis. The role of androgens. 256 37

Thyrotropin-releasing hormone has been reported to increase strength in patients with amyotrophic lateral sclerosis (ALS). DN-1417 is an analog of thyrotropin-releasing hormone, which has less endocrinologic activity, but more anterior horn cell stimulating effect (with no "autorefractory state"). However, 2 mg DN-1417, IM twice a day for 1 month in an open-label trial, produced no objective improvement of strength in nine patients with ALS. No patient entered the double-blind, placebo-controlled phase of the trial.
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PMID:Treatment of amyotrophic lateral sclerosis with the TRH analog DN-1417. 310 20

Thyrotropin-releasing hormone (TRH) potentiated the monosynaptic reflex in isolated spinal cords obtained from 7- to 9-day-old rats. A concentration-dependent increase in the monosynaptic reflex was observed in spinal cords obtained from male but not from female or castrated male rats. In contrast, the magnitude of potentiation in cords from ovariectomized control female rats and in ovariectomized female rats treated with testosterone approached that seen in intact males. The results provide evidence that gender plays a prominent role in the variability of response both of humans with amyotrophic lateral sclerosis and of animal tissues to TRH. Furthermore, exposure to androgen during the neonatal period may determine the responsiveness of motoneurons to TRH. Thus the use of TRH in the treatment of amyotrophic lateral sclerosis may be more effective in males than in females.
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PMID:Gender-specific action of thyrotropin-releasing hormone in the mammalian spinal cord. 311 15

Thyrotropin-releasing hormone (TRH) causes a variety of thyroidal and non-thyroidal effects, the best known being the feedback regulation of thyroid hormone levels. This was employed in the TRH stimulation test, which is currently little used. The role of TRH as a cancer biomarker is minor, but exaggerated responses to TSH and prolactin levels in breast cancer led to the hypothesis of a potential role for TRH in the pathogenesis of this disease. TRH is a rapidly degraded peptide with multiple targets, limiting its suitability as a biomarker and drug candidate. Although some studies reported efficacy in neural diseases (depression, spinal cord injury, amyotrophic lateral sclerosis, etc.), therapeutic use of TRH is presently restricted to spinocerebellar degenerative disease. Regulation of TRH production in the hypothalamus, patterns of expression of TRH and its receptor in the body, its role in energy metabolism and in prolactin secretion are addressed in this review.
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PMID:The forgotten effects of thyrotropin-releasing hormone: Metabolic functions and medical applications. 2993 15