Leuprolide acetate, a GnRH agonist, improves experimental autoimmune encephalomyelitis: a possible therapy for multiple sclerosis

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Leuprolide acetate treatment in rats with experimental autoimmune encephalomyelitis improved clinical signs, body weight, myelin basic protein and neurofilament expression, and axonal morphometry while reducing cell infiltration.

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This paper investigated whether leuprolide acetate, a synthetic GnRH agonist, exerts neurotrophic and therapeutic effects in a rat model of experimental autoimmune encephalomyelitis (EAE), assessing clinical locomotor signs, body weight, neurofilament (NF) and myelin basic protein (MBP) expression, axonal morphometry, and spinal cord immune cell infiltration. Leuprolide acetate treatment reduced the severity of EAE clinical signs, increased body weight gain, elevated MBP and NF expression, increased axonal area, and increased cell infiltration in EAE animals. A major limitation is that the study is focused on a single animal model and relies on preclinical endpoints rather than evaluating long-term outcomes or mechanistic causality. Relevance to endometriosis: leuprolide acetate is cited as having clinical use for endometriosis, uterine fibroids, and other conditions, though the experiments themselves are performed in the context of EAE and multiple sclerosis.

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Abstract

Gonadotrophin-releasing hormone (GnRH), a well known hypothalamic neuropeptide, has been reported to possess neurotrophic properties. Leuprolide acetate, a synthetic analogue of GnRH is considered to be a very safe and tolerable drug and it has been used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. The present study was designed to determine whether Leuprolide acetate administration, exerts neurotrophic effects on clinical signs, body weight gain, neurofilaments (NFs) and myelin basic protein (MBP) expression, axonal morphometry and cell infiltration in spinal cord of experimental autoimmune encephalomyelitis (EAE) rats. In this work, we have found that Leuprolide acetate treatment decreases the severity of clinical signs of locomotion, induces a significantly greater body weight gain, increases the MBP and NFs expression, axonal area and cell infiltration in EAE animals. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.
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Abstract

Gonadotrophin-releasing hormone (GnRH), a well known hypothalamic neuropeptide, has been reported to possess neurotrophic properties. Leuprolide acetate, a synthetic analogue of GnRH is considered to be a very safe and tolerable drug and it has been used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. The present study was designed to determine whether Leuprolide acetate administration, exerts neurotrophic effects on clinical signs, body weight gain, neurofilaments (NFs) and myelin basic protein (MBP) expression, axonal morphometry and cell infiltration in spinal cord of experimental autoimmune encephalomyelitis (EAE) rats. In this work, we have found that Leuprolide acetate treatment decreases the severity of clinical signs of locomotion, induces a significantly greater body weight gain, increases the MBP and NFs expression, axonal area and cell infiltration in EAE animals. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis. Similar content being viewed by others

References

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We thank to the Consejo Nacional de Ciencia y Tecnología (CONACyT) for scholarship 266788. Conflict of interest The authors declare that they have no conflict of interest. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Guzmán-Soto, I., Salinas, E., Hernández-Jasso, I. et al. Leuprolide Acetate, a GnRH Agonist, Improves Experimental Autoimmune Encephalomyelitis: A Possible Therapy for Multiple Sclerosis. Neurochem Res 37, 2190–2197 (2012). https://doi.org/10.1007/s11064-012-0842-x Received: Revised: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s11064-012-0842-x

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endometriosis

MeSH descriptors

Encephalomyelitis, Autoimmune, Experimental Gonadotropin-Releasing Hormone Leuprolide Multiple Sclerosis Animals Encephalomyelitis, Autoimmune, Experimental Female Gonadotropin-Releasing Hormone Leuprolide Leuprolide Multiple Sclerosis Rats Rats, Inbred Lew

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