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Pesquisa
Webinar - "Growth Hormone Therapy - Past, Present and Future"
Local: Online
Dia: 3 de Março de 2022
Organização: SPEDP
Temática: "Growth Hormone Therapy - Past, Present and Future"
Resumo: Summary of presentation During the 19th century, the link was made between the pituitary gland and linear growth in children and adolescents. The secretion of a pituitary hormone and the chemical structure of this hormone, called growth hormone (GH), was established by CH Li at the University of California, San Francisco by 1945. Previously an extract of bovine GH had been injected into hypopituitary rats and linear growth had been demonstrated. However the effect of extracted GH on humans was species-specific and only human GH (hGH) could induce this. In 1958, Raben, from Tufts University, USA, demonstrated that hGH extracted from human cadaver pituitary glands could stimulate linear growth in humans with hypopituitarism. This heralded an era of purification and extraction of hGH and treatment of children with severe GH deficiency. Growth promotion was soon induced clinically with agencies for cadaver pituitary extraction established in many countries. In 1985, a neurodegenerative disorder Creutzfeldt-Jakob disease (CJD) was reported in a young man treated with extracted hGH in California. CJD was caused by an infectious agent known as a prion, which had infected human pituitaries and was not removed by the hGH purification process and therefore transmitted to humans. A total of 226 global cases, mostly fatal, were diagnosed. Human extracted hGH therapy was immediately suspended. Fortunately, genetic engineering had developed a recombinant form of hGH which was safe and could be produced on an industrial scale. The era of rhGH therapy began. The FDA rapidly licensed rhGH for GH deficiency in children and several other growth disorders such as, Turner syndrome (TS), short stature due to birth size small for gestational age (SGA), idiopathic short stature (ISS), chronic renal insufficiency (CRI) and Prader-Willi syndrome. Daily rhGH therapy became established in these disorders. International databases(eg KIGS, NCGS and Nordinet) were established which gave useful efficacy data and confirmed long-term safety. In 1999, the first growth prediction models were published and led to individualisation of rhGH therapy for each condition and for each patient according to established predictive factors. Late diagnosis, particularly of GH deficiency and TS, together with unsatisfactory responses and poor adherence to rhGH remain common unmet clinical needs in the field of growth management. The concept of long-acting rhGH (LArhGH) was explored 15 years ago using microspheres but was unsuccessful. During the last 5 years LArhGH has been further developed using different technologies. First absorption of rhGH can be delayed by conjugating the hGH molecule to polyethylene glycol (PEG). Secondly, hGH can be fused to amino acids to delay its absorption and thirdly it can be fused to C-terminal peptides, as occurs naturally with human chorionic gonadotrophin. Four main contenders for approval by the FDA and EMA for injection on a once- weekly basis currently exit. These are Jintralong, a pegylated formulation, made by Gen Sciences and approved in China, Transcon LArhGH made by Ascendis, Somapacitan made by Novo Nordisk and Somatrogon made by Pfizer-OPKO. It is likely that FDA and EMA licensing will be approved for GH deficiency in 2022. A GH secretagogue which induces increased GH pulsatility is currently in Phase II studies. The aim of this new treatment will be to improve adherence and subsequently efficacy. The new dawn of LArhGH therapy is dawning.
Site de Internet: www.spedp.pt
Temática: "Growth Hormone Therapy - Past, Present and Future"
Resumo: Summary of presentation During the 19th century, the link was made between the pituitary gland and linear growth in children and adolescents. The secretion of a pituitary hormone and the chemical structure of this hormone, called growth hormone (GH), was established by CH Li at the University of California, San Francisco by 1945. Previously an extract of bovine GH had been injected into hypopituitary rats and linear growth had been demonstrated. However the effect of extracted GH on humans was species-specific and only human GH (hGH) could induce this. In 1958, Raben, from Tufts University, USA, demonstrated that hGH extracted from human cadaver pituitary glands could stimulate linear growth in humans with hypopituitarism. This heralded an era of purification and extraction of hGH and treatment of children with severe GH deficiency. Growth promotion was soon induced clinically with agencies for cadaver pituitary extraction established in many countries. In 1985, a neurodegenerative disorder Creutzfeldt-Jakob disease (CJD) was reported in a young man treated with extracted hGH in California. CJD was caused by an infectious agent known as a prion, which had infected human pituitaries and was not removed by the hGH purification process and therefore transmitted to humans. A total of 226 global cases, mostly fatal, were diagnosed. Human extracted hGH therapy was immediately suspended. Fortunately, genetic engineering had developed a recombinant form of hGH which was safe and could be produced on an industrial scale. The era of rhGH therapy began. The FDA rapidly licensed rhGH for GH deficiency in children and several other growth disorders such as, Turner syndrome (TS), short stature due to birth size small for gestational age (SGA), idiopathic short stature (ISS), chronic renal insufficiency (CRI) and Prader-Willi syndrome. Daily rhGH therapy became established in these disorders. International databases(eg KIGS, NCGS and Nordinet) were established which gave useful efficacy data and confirmed long-term safety. In 1999, the first growth prediction models were published and led to individualisation of rhGH therapy for each condition and for each patient according to established predictive factors. Late diagnosis, particularly of GH deficiency and TS, together with unsatisfactory responses and poor adherence to rhGH remain common unmet clinical needs in the field of growth management. The concept of long-acting rhGH (LArhGH) was explored 15 years ago using microspheres but was unsuccessful. During the last 5 years LArhGH has been further developed using different technologies. First absorption of rhGH can be delayed by conjugating the hGH molecule to polyethylene glycol (PEG). Secondly, hGH can be fused to amino acids to delay its absorption and thirdly it can be fused to C-terminal peptides, as occurs naturally with human chorionic gonadotrophin. Four main contenders for approval by the FDA and EMA for injection on a once- weekly basis currently exit. These are Jintralong, a pegylated formulation, made by Gen Sciences and approved in China, Transcon LArhGH made by Ascendis, Somapacitan made by Novo Nordisk and Somatrogon made by Pfizer-OPKO. It is likely that FDA and EMA licensing will be approved for GH deficiency in 2022. A GH secretagogue which induces increased GH pulsatility is currently in Phase II studies. The aim of this new treatment will be to improve adherence and subsequently efficacy. The new dawn of LArhGH therapy is dawning.
Programa: (PDF 237 KB)
Secretariado: geral@spedp.ptSite de Internet: www.spedp.pt
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