Sermorelin: Beyond Growth Hormone Stimulation

Sermorelin is a synthetic (man-made) version of a naturally occurring substance that causes release of growth hormone from the pituitary gland. Growth hormone is naturally produced by the pituitary gland and is necessary for growth in children. In children who fail to grow normally because their bodies are not producing enough growth hormone, this medicine may be used to increase the amount of growth hormone produced by the pituitary gland.

Sermorelin as management of adult-onset growth

Growth hormone replacement therapy (GHRT) using recombinant human growth hormone (rhGH) has been embraced by many age management practitioners as one of the most effective methods for opposing somatic senescence currently available. However, its routine use has been controversial because few clinical studies have been performed to determine the potential risks of long-term therapy. One possibility that is receiving growing attention is the use of GH secretagogues to promote pituitary health and function during aging. An example of such molecules is growth hormone releasing factor 1–29 NH2-acetate, or sermorelin, that recently became available to practitioners for use in longevity medicine  Other alternatives include orally active growth hormone-releasing peptides that are currently being developed by pharmaceutical companies. Some of these have been reported to be effective at improving physical performance in the elderly (Fahy 2006). However, it is unlikely that they will be marketed for several years. On the other hand, sermorelin, an analog of naturally occurring growth hormone-releasing hormone (GHRH) whose activity declines during aging, may presently offer a more immediate and better alternative to rhGH for GHRT in aging.[1]

Growth-deficient children need higher doses of growth hormone than can be achieved by stimulating production of their own hormone, whereas the beneficial effects of sermorelin on pituitary function and simulation of youthful growth hormone secretory dynamics in aging adults have little effect on growth rate in children. Unlike exogenous rhGH that causes production of the bioactive hormone IGF-1 from the liver, sermorelin simulates the patients own pituitary gland by binding to specific receptors to increase production and secretion of endogenous hGH. Finally, there is the question of lawful practice. Unlike rhGH which has legal restrictions on its clinical use, the off-label prescribing of sermorelin is not prohibited by federal law. Thus, it can be carefully employed and evaluated by the practitioner to objectively determine whether it provides greater benefits with less risk to his/her patients. In support of this effort, the Society for Applied Research in Aging will be providing sermorelin free of cost on a competitive basis to practitioners willing to study its effects under protocol conditions and to report the outcomes in a peer-reviewed journal such as Clinical Interventions in Aging. Hopefully, through such efforts we can contribute to development of a paradigm for evidence-based GHRT in clinical age management.

Sermorelin is A potentially effective drug for patients with recurrent glioma

Glioma is the most common primary tumor of the central nervous system (1). Although with the improvement of medical technology, the tumor could be nearly totally resected, and post-operative supplemented with a series of comprehensive treatment such as radiotherapy and chemotherapy. Therefore, how to use the existing marketed drugs to treat patients with recurrent glioma became an achievable and convenient method. In this study, 4,865 drugs and the CGGA databases containing sequencing information of primary and recurrent gliomas patients were used to high-throughput drug screening for recurrent gliomas. Finally, we found that sermorelin was the most effective drug for recurrent gliomas. Sermorelin is a synthetic growth hormone releasing hormone (GHRH) composed of 29 amino acids with a relative molecular weight of 3,357.88. It is the amino-terminal fragment of endogenous GHRH and has a significant effect on regulating growth. Through further analysis, we found that sermorelin is more suitable for patients with much malignant molecular phenotypes, including WHO grade IV, IDH wildtype, 1p/19q non-codeletion, and mesenchymal subtype gliomas. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses found that the Drug Resistance Score (DRS) of sermorelin was negatively correlated with cell proliferation and immune function.[2]

We acquired the drug sermorelin via the above analysis. As a GHRH analog, it stimulates GHRHR to play a regulatory role. It could penetrate the blood-brain barrier easily accompanied by fewer side effects. It is ideal for treating patients with recurrent glioma. Interestingly, our analysis also found that patients with stronger malignant phenotypes were more sensitive to sermorelin. Patients with gliomas of IDH wildtype, 1p/19q non-codeletion, and mesenchymal subtype had worse prognoses and shorter average survival time. Our analysis revealed that it could inhibit transcription and translation of tumor cells by regulating the cell cycle and nuclear division. Malignant tumors grow fast due to their rapid propagation capability and thus are more sensitive to sermorelin. The previous study demonstrated that the combination of GHRH agonist JI-34 and doxorubicin can inhibit the growth of glioma cell line U-87 by reducing the expression of apoptosis genes in vivo and in vitro (10). Schally et al. also found that GHRH agonist MR409 inhibited the growth of various human-derived tumor cells by down-regulating GHRHR. The DRS of sermorelin was lower in these patients meaning that these patients were more sensitive to it. Patients in this category will benefit more from treatment with sermorelin. Meanwhile, our analysis also revealed that it was related to immune function. The stronger enrichments of immune checkpoints features and M0 macrophages, and the lower DRS of the sermorelin means the greater sensitivity to sermorelin.

References

[1]Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. 2006;1(4):307-8. doi: 10.2147/ciia.2006.1.4.307. PMID: 18046908; PMCID: PMC2699646.

[2]Chang Y, Huang R, Zhai Y, Huang L, Feng Y, Wang D, Chai R, Zhang W, Hu H. A potentially effective drug for patients with recurrent glioma: sermorelin. Ann Transl Med. 2021 Mar;9(5):406. doi: 10.21037/atm-20-6561. PMID: 33842627; PMCID: PMC8033379.

You may like