Perspectives on long-acting growth hormone therapy in children and adults

Lal, Rayhan; Hoffman, Andrew R.

doi:10.20945/2359-3997000000190

Cited by 28 publications

(21 citation statements)

References 47 publications

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“…The effects of rhGH on the disproportion between the limbs and trunk are largely unknown. The same meta-analysis noted above found only 2 studies in which sitting height was properly evaluated ( 177 ). It progressively increased over 24 months (n=50 children) from -1.5 SD (95% CI -2.4 to -0.58 SD) to -0.47 SD (95% CI -1.2 to +0.22).…”

Section: Some Other Conditions For Which Rhgh Has Been Studied But Do Not Have Fda Approvalmentioning

confidence: 89%

“…Thus, the potential availability of long-acting GH (LAGH) preparations, if safe and effective, would be an advantage to overcome the difficulties of requiring daily injections. Two detailed reviews discussing LAGH data ( 177 , 180 ) and a meta-analysis ( 181 ) comparing LAGH to daily treatment provide information about the various formulations that are becoming available. We will briefly describe a few of these.…”

Section: Long-acting Ghmentioning

confidence: 99%

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Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future

2021

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Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic surgery and multiple pharmacologic agents. Virtually at the same time experiments with the removal of the pituitary from laboratory animals noted the slowing or stopping of linear growth and then over a few decades the extraction and purification of a protein within the anterior pituitary that restored, partially or in full, the animal’s growth. Human growth hormone was purified decades after those from large animals and it was noted that it was species specific, that is, only primate growth hormone was metabolically active in primates. That was quite unlike the beef and pork insulins which revolutionized the care of children with diabetes mellitus. A number of studies included mild enzymatic digestion of beef growth hormone to determine if those “cores” had biologic activity in primates and man. Tantalizing data showed minimal but variable metabolic efficacy leading to the “active core” hypothesis, for these smaller peptides would be amenable to peptide synthesis in the time before recombinant DNA. Recombinant DNA changed the landscape remarkably promising nearly unlimited quantities of metabolically active hormone. Eight indications for therapeutic use have been approved by the Food and Drug Administration and a large number of clinical trials have been undertaken in multiple other conditions for which short stature in childhood is a sign. The future predicts other clinical indications for growth hormone therapy (and perhaps other components of the GH?IGF-1 axis), longer-acting analogues and perhaps a more physiologic method of administration as virtually all methods at present are far from physiologic.

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Section: Some Other Conditions For Which Rhgh Has Been Studied But Do Not Have Fda Approvalmentioning

confidence: 89%

Section: Long-acting Ghmentioning

confidence: 99%

Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future

2021

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“…140,141 Nonetheless, its use is limited by its short serum half-life (tens of minutes to several hours after intravenous or subcutaneous injection, respectively), 142 which mandates frequent administration. 143 Significant effort has been devoted to developing long-acting hGH to overcome this limitation, 144 including Jintrolong, which bears a 40-kDa branched PEG at its N-terminus and was approved for use to treat pediatric hGH deficiency in China in 2017. 145,146 In 2011, Ambrx and collaborators used a Tyr analog OTS(CUA) to install a single AcF at 20 different positions of hGH (Figure 5), with sequence context-dependent yields of 20−70% relative to the natural protein.…”

Section: ■ Comparison Of the Two Methods For Gcementioning

confidence: 99%

“…148 Nonetheless, due to PEG accumulation in cells of the choroid plexus in primates, and possibly the increasing availability of convenient daily injectables, the development of ARX201 was halted in 2014. 144 Leptin. Diet-induced obesity, and its associated disorders such as type 2 diabetes and non-alcoholic fatty acid liver diseases, the most common being non-alcoholic steatohepatitis (NASH), represent an emerging overwhelming health crisis.…”

Section: ■ Comparison Of the Two Methods For Gcementioning

confidence: 99%

Genetic Code Expansion: Inception, Development, Commercialization

Manandhar¹,

Chun²,

Romesberg³

2021

J. Am. Chem. Soc.

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Virtually all natural proteins are built from only 20 amino acids, and while this makes possible all the functions they perform, the ability to encode other amino acids selected for specific purposes promises to enable the discovery and production of proteins with novel functions, including therapeutic proteins with more optimal drug-like properties. The field of genetic code expansion (GCE) has for years enabled the production of such proteins for academic purposes and is now transitioning to commercialization for the production of more optimal protein therapeutics. Focusing on E. coli, we review the history and current state of the field. We also provide a review of the first generation commercialization efforts, the lessons learned, and how those lessons are guiding new efforts. With continued academic and industrial progress, GCE methodologies promise to make possible the routine optimization of proteins for therapeutic use in a way that has only previously been possible with small-molecule therapeutics.

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“…The depot preparation, however, was a highly viscous formulation with somatropin-containing microparticles and was associated with a high degree of injection site reaction ( 7 ). The depot preparation needed to be injected with a large-bore needle, often more than once at a given administration interval and leaving a visible subcutaneous lump ( 8 ). Lonapegsomatropin injections, in contrast, are well-tolerated and readily administered using an autoinjector and fine-gauge needle ( 2 ).…”

mentioning

confidence: 99%