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

We have studied effects of TRH analogue, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) (from Tanabe, Osaka, Japan) on explanted ventral and dorsal spinal cord cultures from 13- and 14-day-old rat embryos. TA-0910-treated cultures had significantly increased neurite outgrowth with cultures of ventral spinal cord, but not with cultures of dorsal spinal cord. The effect was dose-dependent. A possible role for TRH in amyotrophic lateral sclerosis remains to be defined.
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PMID:TRH analogue, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) enhances neurite outgrowth in rat embryo ventral spinal cord in vitro. 146 25

This study presents the experience of one year of treatment in patients with amyotrophic lateral sclerosis, with intrathecal TRH administered daily by a subcutaneous reservoir connected to the intrathecal lumbar space by a double catheter system as to provide continuous circulation of CSF and to avoid sac formation since this would be a source of infection. Clinical evaluation was carried out with a scale developed by the authors with the main aim of evaluating the loss of vital motor abilities and not as a localized evaluation. Secondary effects due to the implantation of the reservoir in addition to its use are presented although data were not important. Intrathecal administration of TRH was carried out similarly (600 micrograms/day) with secondary effects being the same as those by other routes of administration although of a lesser intensity. The results of the clinical evaluation at the beginning and end of the treatment as well as after patient follow up demonstrated that beneficial effects do not occur equally in all patients but rather are transitory and do not improve the natural evolution of the disease. The authors conclude that, methodologically, this series study does not enter within the frame of an advisable statistical study since the aim is to provide data for a future controlled study.
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PMID:[Treatment of amyotrophic lateral sclerosis with daily intrathecal TRH. A year's experience. Pilot study II]. 159 3

Seven patients, six suffering from amyotrophic lateral sclerosis (ALS) and one from Friedreich ataxia, were treated with a placebo i.v. infusion during the first day and with TRH-T i.v. infusion at a rate of 2 mg/h for 8 h daily (total daily dosage 16 mg) on the 2 consecutive days. Continuous blood pressure (BP) and EKG monitorings were performed during 3 days infusion. Blood samples were collected for endocrinological evaluations. The neurological evaluation after acute TRH-T treatment showed an objective improvement in 3 of the 8. We found significantly higher values of systolic (max. difference of 10.1 mm Hg) and diastolic (max. difference of 8.8 mm Hg) BP than during placebo, beginning from the 5th h of the infusion (p less than 0.05). A trend in progressive increase of the heart rate (HR) reached statistical significance (p less than 0.01) at the 8th h of the second TRH-T infusion. The cardiovascular changes during the i.v. continuous TRH-T infusions were clinically irrelevant and never required the interruption of the treatment.
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PMID:Continuous intravenous infusion of TRH-T: clinical, cardiovascular and endocrinological effects. 179 54

A 64-year-old woman who had amyotrophic lateral sclerosis (ALS) with disturbance of vertical ocular movement was presented. She was admitted to our hospital with progressive dysphagia, dysarythria and weakness of the extremities. Neurological examinations revealed disturbance of vertical ocular movement with normal doll's eye phenomenon (supranuclear origin), bulbar palsy, muscle weakness of the extremities, extensor plantar signs, and fasciculations of the costal and interosseal muscles. EMG studies showed denervation potentials, and muscle biopsy demonstrated group atrophy, fiber type grouping and small angular fibers. TRH injections resulted in improvement of disturbance of vertical ocular movement, but no effect was seen on the weakness of the limb. There was about 20 Japanese cases with disturbance of ocular movement in ALS, but it was rare to see ocular movement disorder from the early stage of ALS. The pathophysiology of ocular movement disorder in ALS has been thought to be due to supranuclear origin, i.e., the disturbance in the pathway from the frontal cortex to the mesencephalon. In this case, TRH might effect at some point of the frontomesencephalic pathway.
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PMID:[A case of amyotrophic lateral sclerosis with disturbance of vertical ocular movement responding to thyrotropin releasing hormone (TRH)]. 190 37

30 subjects--23 with amyotrophic lateral sclerosis (ALS), 4 with Charcot-Marie Tooth atrophy, 2 with progressive spinal muscle atrophy and 1 with radiation myelopathy--were given chronic low-dose TRH therapy. The effects of treatment were assessed on the scale of Norris et al. (1974). The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases.
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PMID:Low doses of TRH in amyotrophic lateral sclerosis and in other neurological diseases. 190 41

In six patients suffering from amyotrophic lateral sclerosis we evaluated changes of T4, T3, TSH, PRL, and GH during treatment by continuous iv infusion of TRH for at least 15 days. No clinical improvement was detected. A significant rise of thyroid hormone levels was observed, as well as an upward trend of basal TSH levels and no change of basal PRL and GH levels. TRH acute test-induced TSH and PRL responses became blunted. Treatment provoked also the onset of a responsiveness of PRL to GHRH. The reduced TSH and PRL responses to acute TRH test during treatment could be explained by a down-regulation of TRH pituitary receptors. On the contrary, the onset of PRL responsiveness to GHRH is at present without a satisfactory explanation.
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PMID:Prolactin response to growth hormone-releasing hormone during chronic thyrotropin-releasing hormone infusion in the treatment of amyotrophic lateral sclerosis. 212 10

The blood serum TSH and PRL levels were studied in 12 ALS patients after TRH stimulation. The TSH test was repeated after 4-weeks TRH treatment. The results were compared with the data obtained in the control group. It was shown that after TRH stimulation the TSH responses did not reveal greater abnormalities, but PRL responses were significantly diminished. The results could confirm our previous observations concerning the dysregulation of dopamine metabolism in ALS patients.
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PMID:[Effect of thyroliberin treatment on the thyrotropin and prolactin levels in patients with amyotrophic lateral sclerosis]. 213 51

The lack of effective therapy for many of the chronic neuromuscular diseases such as amyotrophic lateral sclerosis, hereditary motor sensory neuropathy (Charcot-Marie-Tooth disease), spinocerebellar degenerations and idiopathic polyneuropathy has led to a search for substances that may stimulate peripheral nerve regeneration. Two such agents that have been proposed are gangliosides (mixed purified bovine brain gangliosides, Cronassial) and thyrotropin releasing factor (TRH). Studies on both of these agents were initially reported with enthusiasm to be successful, but later double-blind controlled studies have failed to confirm these findings. This review provides critical analysis of the designs of studies of potentially effective agents in chronic neuromuscular diseases, and emphasizes the power of the placebo response, and the importance of designing placebos which are indistinguishable from the trial medication other than in the active effect.
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PMID:Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. 223 70

The results of the various studies and an analysis of the methodology are presented in TABLE 1. As can be seen, there was no "perfect" study. In five of the studies enough information was presented with regard to the measurements and the behavior of control patients that a statistical analysis could be performed. Three of the studies showed a transient, statistically significant effect in at least some muscles. The two studies that demonstrated no such effect both used TRH in very small doses. It therefore seems reasonable to conclude that the effect of TRH in ALS is a definite, acute, and transient response. The cause of this response, however, has not been documented, and whether it is associated with an effect of the drug on the disease process remains to be seen.
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PMID:Thyrotropin-releasing hormone in ALS. Are the results of clinical studies inconsistent? 249 84

The critical points that must be addressed in evaluating ergotropic drugs are exemplified by the current morass of positive and negative results that have been obtained in clinical investigations of TRH or its analogues. Appropriate subject selection is crucial. These patients may have bulbar symptoms, and those features of ALS should be specifically assayed for treatment effects relative to placebo. Gender-specific effects of TRH need to be accounted for in study design. In addition, electrophysiological techniques such as single fiber density may help determine the responsiveness of patients to TRH or its analogues. The clinical significance of an increase in fiber density following TRH or other drugs should be determined, as it will provide insight into the state of motor neurons in the spinal cord of patients with ALS and possibly could be important in determining those who may respond to TRH if such a response is possible. Clinical studies have quite clearly shown conflicting results. Basic studies, however, have shown that response to TRH is state dependent, that is, whether the patient is male or female. Clinical studies have shown that response to TRH is state dependent, that is, it depends on whether the patient has bulbar or nonbulbar signs and is male or female. Future studies must take into consideration this state dependence as a specific feature of the pharmacological action of TRH and its analogues.
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PMID:A summary of the current position of TRH in ALS therapy. 249 85


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