Intravenous Thyrotropin Releasing Hormone in Amyotrophic Lateral Sclerosis: Autonomic Effects

Beaulieu, Debra A.; Erickson, L.; Williams, Ashley; Sufit, Robert; Brooks, Benjamin Rix

doi:10.1016/s0733-8619(18)30927-7

Cited by 5 publications

(1 citation statement)

References 29 publications

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“…In rats, taltirelin has been proven to be a survival factor for developing spinal motor neurons [ 55 ], and enhanced neurite outgrowth in a rat embryo ventral spinal cord [ 56 ]. Although the autonomic effects were not significant in some studies [ 57 ], the undesired side effects depended on the specific features of the disease [ 58 ]. Even if these results seemed favorable, some studies found no significant effects after TRH administration [ 59 ]; moreover, the transitory, inconsistent, and sex-dependent responses [ 60 , 61 ] overshadowed interest in the peptide as a therapeutic agent for this complex disease.…”

Section: Introductionmentioning

confidence: 99%

New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent

Alvarez-Salas

García-Luna

Gortari

2023

IJMS

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Thyrotropin-releasing hormone (TRH) is a tripeptide that regulates the neuroendocrine thyroid axis. Moreover, its widespread brain distribution has indicated that it is a relevant neuromodulator of behaviors such as feeding, arousal, anxiety, and locomotion. Importantly, it is also a neurotrophic peptide, and thus may halt the development of neurodegenerative diseases and improve mood-related disorders. Its neuroprotective actions on those pathologies and behaviors have been limited due to its poor intestinal and blood–brain barrier permeability, and because it is rapidly degraded by a serum enzyme. As new strategies such as TRH intranasal delivery emerge, a renewed interest in the peptide has arisen. TRH analogs have proven to be safe in animals and humans, while not inducing alterations in thyroid hormones’ levels. In this review, we integrate research from different approaches, aiming to demonstrate the therapeutic effects of TRH, and to summarize new efforts to prolong and facilitate the peptide’s actions to improve symptoms and the progression of several pathologies.

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Section: Introductionmentioning

confidence: 99%

New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent

Alvarez-Salas

García-Luna

Gortari

2023

IJMS

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Motor Neuron Disease

Brooks¹,

DePaul²,

Tan³

et al. 1990

Foundations of Neurology

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A Summary of the Current Position of TRH in ALS Therapy

Brooks¹

1989

Ann NY Acad Sci

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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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Intravenous Thyrotropin Releasing Hormone in Amyotrophic Lateral Sclerosis: Autonomic Effects

Cited by 5 publications

References 29 publications

New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent

New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent

Motor Neuron Disease

A Summary of the Current Position of TRH in ALS Therapy

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