Description of Tesamorelin

Tesamorelin, a polypeptide consisting out of 44 amino acids of GHRH is specific for addition of trans-3-hexanoic acid to the peptide’s sequence, which makes the compound more stable in human plasma and also increases its half-life. Tesamorelin has been found effective in reducing visceral adiposity in patients with lipodystrophy, leading to its approval for clinical use in the United States in 2010. It was developed by Theratechnologies, Inc., and was not intended for weight loss or treatment of obesity but specifically targeted the reduction of excess abdominal fat associated with HIV medication-induced lipodystrophy. Its major effects are related to glucose and lipid metabolism, and it is being evaluated as a treatment of insulin resistance, nonalcoholic fatty liver, peripheral nerve regeneration or cardiovascular diseases. Lets have a look at several research results in the field of tesamorelin effects.

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Research Confirmed Effects

1. Tesamorelin in Lypodystrophy

Tesamorelin, a synthetic analog of growth hormone-releasing factor, addresses excess visceral adipose tissue (VAT) in patients with HIV-associated lipodystrophy, a condition characterized by body composition changes, including lipohypertrophy. Lipodystrophy adversely impacts patients' quality of life and is often linked to antiretroviral therapy (ART), particularly protease inhibitors. Tesamorelin's efficacy in reducing VAT has been demonstrated through randomized Phase 3 trials, showing significant reductions in VAT levels over six months of treatment. Notably, patient characteristics such as metabolic syndrome, elevated triglyceride levels, and white race are associated with a higher likelihood of VAT reduction with tesamorelin therapy.

Tesamorelin's approval in 2010 marked a significant advancement in the treatment of HIV-associated lipodystrophy, offering a targeted therapeutic approach to reduce excess adiposity in affected patients. Prior to its availability, treatment options for lipodystrophy were limited, often relying on lifestyle modifications and surgical interventions with varying degrees of success. Tesamorelin's effectiveness in reducing VAT by nearly 20% surpasses that of other available therapies, positioning it as a valuable intervention in managing lipodystrophy-related complications in HIV-infected patients. Thus, tesamorelin is 4 times more effective in reducing adipocity.

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2. Tesamorelin in Cardiac Disease

HIV patients are also at increased risk of developing cardiovascular disease (CVD), mostly due to abnormal fat deposition, and also due to antiretroviral drugs. Tesamorelin demonstrates efficacy in reducing visceral adipose tissue (VAT) and improving metabolic parameters in HIV-infected patients with treatment-associated central fat accumulation. In a 26-week randomized trial involving 412 patients, daily subcutaneous injections of tesamorelin resulted in a significant reduction in VAT by 15.2% compared to a 5.0% increase in the placebo group. Moreover, tesamorelin treatment led to improvements in triglyceride levels, total cholesterol to HDL cholesterol ratio, and insulin-like growth factor I (IGF-I) levels. These metabolic benefits, including reduced VAT and improved lipid profiles, suggest a potential therapeutic role for tesamorelin in managing central fat accumulation in HIV-infected individuals.

Furthermore, responders to tesamorelin therapy, defined as those achieving ≥8% reduction in VAT, experienced greater reductions in triglyceride levels and improvements in glucose homeostasis compared to nonresponders over a 52-week treatment period. Notably, tesamorelin's effects on metabolic parameters are associated with the percentage change in VAT, indicating a direct correlation between VAT reduction and metabolic improvements. These findings underscore the potential of tesamorelin to not only reduce visceral adiposity but also mitigate cardiovascular risk factors in HIV-infected patients, offering a promising therapeutic strategy beyond conventional interventions like statins.

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3. Tesamorelin and GH Deficiency in HIV Patients

Highly active antiretroviral therapy (HAART) is linked with various endocrine and metabolic complications, including altered pituitary growth hormone (GH) secretion in human immunodeficiency virus (HIV) infection, with about one-third of patients exhibiting biochemical GH deficiency (GHD). Patients with HIV often experience reduced spontaneous GH secretion and GH response to stimuli, particularly those with HIV-related lipodystrophy, potentially due to factors like fat accumulation. Although the exact mechanisms underlying GHD in HIV patients are complex and not fully understood, tesamorelin, as a GH releasing hormone analogue, shows promise in reducing visceral fat in HIV-infected individuals with lipodystrophy, offering a safer alternative to high-dose recombinant human growth hormone with fewer side effects.

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4. Tesamorelin and Peripheral Nerve Regeneration

Peripheral nerve injuries lead to motor and sensory deficits with limited therapeutic options available. Growth hormone (GH)-based therapies offer promise in accelerating axonal regeneration and limiting atrophy of denervated muscle and Schwann cells (SCs) before reinnervation, potentially improving outcomes post-surgery. GH-based treatments act on multiple tissues involved in nerve regeneration, offering multi-modal mechanisms and potential secondary benefits for bone, tendon, and wound healing. FDA-approved drugs augmenting the GH axis facilitate potential clinical translation for peripheral nerve injury treatment. Research suggests GH manipulation, like tesamorelin, may improve outcomes, offering potential FDA-approved interventions for this challenging condition.

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5. Tesamorelin in Dementia

The study conducted at the University of Washington School of Medicine involved thirty adults, including those with mild cognitive impairment (MCI), who self-administered daily subcutaneous injections of tesamorelin or placebo for 20 weeks. Brain magnetic resonance imaging and spectroscopy protocols, cognitive testing, and blood sampling were conducted at baseline and weeks 10 and 20, along with glucose tolerance tests before and after intervention. Results showed increased GABA levels in all brain regions, increased NAAG levels in the frontal cortex, and decreased MI levels in the posterior cingulate after 20 weeks of GHRH administration, suggesting a potential mechanism for the favorable effects on cognition observed in adults with MCI and older adults.

This evidence supports the effectiveness of GHRH analogues like tesamorelin in enhancing cognition in early stages of dementia, suggesting a potential avenue for treatment. The findings highlight the modulation of inhibitory neurotransmitter and brain metabolite levels as a mechanism underlying the cognitive benefits observed with GHRH administration. These results not only offer promise for the treatment of dementia but also suggest new directions for research in the quest for a cure or preventative measures against cognitive decline.

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References

1. „LiverTox: Clinical and Research Information on Drug-Induced Liver Injury“, 2018 [Internet].
2. Clinical Review Report: Tesamorelin (Egrifta). Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2016.
3. A. Mangili, J. Falutz, J.-C. Mamputu, M. Stepanians, and B. Hayward, “Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat,” PloS One, vol. 10, no. 10, p. e0140358, 2015. [PubMed]
4. J. Falutz et al., “Metabolic effects of a growth hormone-releasing factor in patients with HIV,” N. Engl. J. Med., vol. 357, no. 23, pp. 2359–2370, Dec. 2007. [NEJM]
5. T. L. Stanley et al., “Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin,” Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am., vol. 54, no. 11, pp. 1642–1651, Jun. 2012. [PubMed]
6. V. Rochira and G. Guaraldi, “Growth hormone deficiency and human immunodeficiency virus,” Best Pract. Res. Clin. Endocrinol. Metab., vol. 31, no. 1, pp. 91–111, 2017. [PubMed]
7. S. H. Tuffaha et al., “Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury,” Expert Opin. Ther. Targets, vol. 20, no. 10, pp. 1259–1265, Oct. 2016. [PubMed]
8. S. D. Friedman et al., “Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging,” JAMA Neurol., vol. 70, no. 7, pp. 883–890, Jul. 2013. [PubMed]