About half of the patients with acute ischemic stroke treated with endovascular thrombectomy (EVT) remain dependent on the help of others or die in the first 90 days. We hypothesize that treatment with ghrelin, started in the first six hours after stroke onset, improves early recovery and long-term functional outcome in these patients. Ghrelin is a naturally occurring hormone and mildly excitatory neurotransmitter also known as the 'hunger hormone.' Treatment with acylated ghrelin consistently improved functional and histological recovery in in vitro and in vivo models of ischemic stroke.

开始日期2023-10-01

申办/合作机构

Rijnstate

NCT05318924 / Recruiting临床1/2期

Will Work for Reward: Effects of Ghrelin Administration on Dopamine and Effort

Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates appetite. Animal studies have conclusively shown that ghrelin increases dopaminergic neurotransmission and, thereby, enhances effort. However, similar evidence on the putative role of ghrelin in humans is still lacking. Here, the investigators propose to conduct a [11C]-raclopride PET/MR study after intravenous administration of ghrelin vs. saline in healthy individuals. First, during an intake visit, the investigators will assess fasting blood levels of hormones involved in appetitive behavior such as ghrelin, leptin, and insulin. In addition, the investigators will conduct a set of tasks that have been associated with dopamine function (i.e., effort and reinforcement learning). Second, the investigators will assess the effects of intravenous administration of ghrelin on dopamine signaling using a double-blind randomized cross-over design. To this end, participants will be infused with ghrelin (vs. saline) while we determine dopamine release (via PET imaging) and assess cerebral blood flow and functional connectivity at rest (via concurrent MR imaging). Furthermore, the investigators will conduct an instrumental motivation task (IMT) where participants have to exert physical effort to obtain rewards. Based on preclinical studies and indirect evidence from human studies, the investigators hypothesize that ghrelin will increase dopamine release in the striatum and that this will, in turn, lead to an increase in the willingness to work for rewards. Moreover, the investigators expect that ghrelin-induced dopamine release will be associated with an elevated tracking of reward utility in the mesolimbic circuit during the IMT, which is known to be associated with response vigor. Collectively, the proposed project would provide a unique resource to test an important link between the gut and the brain in the regulation of appetitive behavior. If ghrelin were to enhance effort expenditure for rewards via dopamine signaling in humans, then restoring sensitivity to ghrelin might be the more promising therapeutic approach compared to antagonizing the ghrelin receptor.

开始日期2022-02-21

申办/合作机构

University Hospital Tübingen

[+1]

NCT04768803 / RecruitingN/AIIT

Circulating Levels of Ghrelin in Patients With a Rare Disease Associated With Intellectual Disability, and Hyperphagia, and / or Overweight, and / or Obesity

A significantly higher proportion of patients with rare diseases (RD) with intellectual disability (ID), present hyperphagia, overweight or obesity, compared to the general population. Prader-Willi syndrome is the only genetic obesity identified to date associated with hyperghrelinemia, while ghrelin levels are lower than in controls in other situations of obesity.
The aim of the study is to find out whether the levels of ghrelin, which are abnormally high in PWS throughout life, are also high in these RD when people have hyperphagia and/or overweight.

开始日期2021-06-10

申办/合作机构

Toulouse University Hospital

100 项与合成生长素相关的临床结果

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100 项与合成生长素相关的转化医学

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100 项与合成生长素相关的专利（医药）

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项与合成生长素相关的文献（医药）

2024-02-20·Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology

Acyl ghrelin, desacyl ghrelin and their ratio affect hepatic steatosis via PPARγ signaling pathway.

Article

作者: Emine Elibol ; Yasemin Akdevelioğlu ; Canan Yılmaz ; Belkıs Narlı ; Serkan Şen ; Gülnur Take Kaplanoğlu ; Cemile Merve Seymen

BACKGROUND AND STUDY AIMS:

Ghrelin is an appetite hormone-containing 28-amino acid and has 4 different forms in the body. Ghrelin forms have different physiological functions in the body. This study aims to analyze the effect of acyl and desacyl ghrelin hormone on hepatic steatosis and biochemical findings in 36 male Wistar rats.

MATERIALS AND METHODS:

Rats were split into 6 equal groups, consisting of control, acyl ghrelin, desacyl ghrelin, acyl/desacyl 3:1, acyl/desacyl 1:1, and acyl/desacyl 1:3 groups, and administered placebo or 200 ng/kg hormone subcutaneous twice a day for 14 days. Oral Glucose Tolerance Test (OGTT) was performed on Day 15, Insulin Tolerance Test (ITT) on Day 16, and scarification procedure on Day 17. Certain biochemical data and liver diacylglycerol (DAG), glycogen, protein kinase C and PPAR-γ levels were detected in the blood. Histological analyses were also conducted on the liver tissues.

RESULTS:

The highest plasma total cholesterol and VLDL-K levels were found in the acyl/desacyl 1:3 group, and lower insulin, and HOMA-IR levels were found in groups where acyl and desacyl were administered together (p < 0.05). PPAR-γ gene expression level increased in acyl ghrelin and acyl/desacyl 1:3 groups compared to the control group. Protein kinase C gene expression was highest in the acyl/desacyl 1:3 group. The most severe degenerative findings compliant with steatosis in the liver were observed in the acyl ghrelin group (p < 0.05).

CONCLUSION:

It was determined that administering rats acyl alone and acyl/desacyl by 1:3 caused the highest PPAR-γ gene expression, serum total cholesterol, HDL-K, and VLDL-K levels in the body. Besides, it is shown that desacyl ghrelin effectively regulates the blood glucose level when administered alone.

2024-01-04·Gene therapy

Ghrelin mediated cardioprotection using in vitro models of oxidative stress.

Article

作者: Cindy Y Kok ; George Ghossein ; Sindhu Igoor ; Renuka Rao ; Tracy Titus ; Shinya Tsurusaki ; James Jh Chong ; Eddy Kizana

Ghrelin is commonly known as the 'hunger hormone' due to its role in stimulating food intake in humans. However, the roles of ghrelin extend beyond regulating hunger. Our aim was to investigate the ability of ghrelin to protect against hydrogen peroxide (H₂O₂), a reactive oxygen species commonly associated with cardiac injury. An in vitro model of oxidative stress was developed using H₂O₂ injured H9c2 cells. Despite lentiviral ghrelin overexpression, H9c2 cell viability and mitochondrial function were not protected following H₂O₂ injury. We found that H9c2 cells lack expression of the preproghrelin cleavage enzyme prohormone convertase 1 (encoded by PCSK1), required to convert ghrelin to its active form. In contrast, we found that primary rat cardiomyocytes do express PCSK1 and were protected from H₂O₂ injury by lentiviral ghrelin overexpression. In conclusion, we have shown that ghrelin expression can protect primary rat cardiomyocytes against H₂O₂, though this effect was not observed in other cell types tested.

2023-12-31·Clinical and experimental hypertension (New York, N.Y. : 1993)

Ghrelin improves endothelial function and reduces blood pressure in Ang II-induced hypertensive mice: Role of AMPK.

Article

作者: Juan Deng ; Yuan Hu ; Yindi Zhang ; Fadong Yu

BACKGROUND:

Endothelial dysfunction is a major pathophysiology observed in hypertension. Ghrelin, a key regulator of metabolism, has been shown to play protective roles in cardiovascular system. However, whether it has the effect of improving endothelial function and lowering blood pressure in Ang II-induced hypertensive mice remains unclear.

METHODS:

In this study, hypertension was induced by continuous infusion of Ang II with a subcutaneous osmotic pumps and ghrelin (30 μg/kg/day) was intraperitoneal injection for 4 weeks. Acetylcholine-induced endothelium-dependent relaxation in aortae was measured on wire myograph and superoxide production in mouse aortae was assessed by ﬂuorescence imaging.

RESULTS:

We found that ghrelin had protective effects on Ang II-induced hypertension by inhibiting oxidative stress, increasing NO production, improving endothelial function, and lowering blood pressure. Furthermore, ghrelin activated AMPK signaling in Ang II-induced hypertension, leading to inhibition of oxidative stress. Compound C, a specific inhibitor of AMPK, reversed the protective effects of ghrelin on the reduction of oxidative stress, the improvement of endothelial function and the reduction of blood pressure.

CONCLUSIONS:

our findings indicated that ghrelin protected against Ang II-induced hypertension by improving endothelial function and lowering blood pressure partly through activating AMPK signaling. Thus, ghrelin may be a valuable therapeutic strategy for hypertension.

项与合成生长素相关的新闻（医药）

2024-03-20

·GlobeNewswire-Health Care

Lumos Pharma Announces that the USPTO Has Granted Patent Protection for Novel Formulation of LUM-201, Extending Exclusivity to 2042

AUSTIN, Texas, March 20, 2024 (GLOBE NEWSWIRE) -- Lumos Pharma, Inc. (NASDAQ:LUMO), a biopharmaceutical company advancing an oral therapeutic candidate for Pediatric Growth Hormone Deficiency (PGHD) through Phase 2 clinical trials, announced that on Thursday, March 14, 2024, the Company received a Notice of Allowance from the US Patent and Trade Office (USPTO) for claims in its patent application number PCT/US22/050700 titled “Compactable Oral Formulations of Ibutamoren.” This patent contains claims directed to certain improved formulations of LUM-201 the Company intends to utilize in its Phase 3 trial and ultimately commercialize. This grant of this novel formulation patent extends intellectual property protection through November 2042 for these improved versions of LUM-201 drug product. “We are excited to announce that LUM-201 has been granted a novel formulation patent by the USPTO, which is enabled by unique properties of this molecule achieved through our improved manufacturing processes,” said Rick Hawkins, Lumos Pharma’s Chairman and CEO. “Importantly, this new patent extends our exclusivity of LUM-201 through 2042, surpassing our current method of use patent expiration in 2036. This novel formulation of LUM-201 permits a capsule with mini-tablets, which should reduce dose variance and enable easier administration for younger children. We intend to employ this formulation in our upcoming Phase 3 trial evaluating oral LUM-201 in moderate pediatric growth hormone deficiency (PGHD) expected to start in Q4 2024, and eventually in the commercial setting following potential regulatory approval of LUM-201.” About LUM-201 LUM-201 (ibutamoren) is an orally administered small molecule that promotes the secretion (secretagogue) of Growth Hormone (GH) from the pituitary gland.1 LUM-201 acts as an agonist of the GH Secretagogue Receptor to stimulate GH release and to suppress the release of somatostatin.2 LUM-201 has been observed to increase the amplitude of endogenous pulsatile GH secretion in humans, which mimics the natural pattern of GH secretion. 3,4 This therapeutic candidate has been studied in more than 1,300 patients, both adult and pediatric, and was generally well tolerated with the most commonly reported adverse events being digestive systems events, including appetite increase. Mild elevations in liver enzymes without accompanying changes in bilirubin were also reported. LUM-201 has received Orphan Drug Designation in both the US and EU. About Lumos Pharma Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. The Company was founded and is led by a management team with longstanding experience in rare disease drug development. Lumos Pharma’s lead therapeutic candidate, LUM-201, is a novel, oral growth hormone (GH) secretagogue, seeking to transform the ~$4.7B global GH market from injectable to oral therapy. LUM-201 is currently being evaluated in multiple Phase 2 clinical studies in Pediatric Growth Hormone Deficiency (PGHD) and has received Orphan Drug Designation in both the US and EU. For more information, please visit https://lumos-pharma.com/. 1 Patchett A.A., et al. Design and Biological Activities of L-163,191 (MK-0677): A Potent, Orally Active Growth Hormone Secretagogue, Proc Natl Acad Sci, 1995, 92:7001-7005. 2 Howard A.D., et al. A Receptor in Pituitary and Hypothalamus that Functions in Growth Hormone Release, Science, 1996, 273:974-977. 3 Nass R., et al. Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults, Ann Intern Med, 2008, 149:601-611. 4 Chapman I.M., et al. Oral Administration of Growth Hormone (GH) Releasing Peptide-Mimetic MK-677 Stimulates the GH/Insulin-Like Growth Factor-I Axis in Selected GH-Deficient Adults, J Clin Endocrinol Metab, 1997, 82(10):3455-3463. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements of Lumos Pharma, Inc. that involve substantial risks and uncertainties. All such statements contained in this press release are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. A law that, in part, gives us the opportunity to share our outlook for the future without fear of litigation if it turns out our predictions were not correct. We are passionate about our business - including LUM-201 and the potential it may have to help patients in the clinic. This passion feeds our optimism that our efforts will be successful and bring about meaningful change for patients. Please keep in mind that actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. We have attempted to identify forward-looking statements by using words such as “projected,” "upcoming," "will," “would,” “should,” "plan," “intend,” "anticipate," "approximate," "expect," “potential,” “imminent,” and similar references to future periods or the negative of these terms. Not all forward-looking statements contain these identifying words. Examples of forward-looking statements include, among others, statements we make regarding the advancement of oral LUM-201 to Phase 3, the potential for LUM-201 to be the first oral therapeutic for PGHD, and any other statements other than statements of historical fact. We wish we were able to predict the future with 100% accuracy, but that just is not possible. Our forward-looking statements are neither historical facts nor assurances of future performance. You should not rely on any of these forward-looking statements and, to help you make your own risk determinations, we have provided an extensive discussion of risks that could cause actual results to differ materially from our forward-looking statements including risks related to the continued analysis of data from our LUM-201 Trials, the timing and outcome of our future interactions with regulatory authorities including our end of Phase 2 meeting with the FDA, the timing and ability of Lumos to raise additional equity capital as needed to fund our Phase 3 Trial, our ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the ability to structure our Phase 3 trial in an effective and timely manner, the ability to successfully develop our product candidate, the effects of pandemics, other widespread health problems or military conflicts including the Ukraine-Russia conflict and the Middle East conflict and other risks could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements including information in the "Risk Factors" section and elsewhere in Lumos Pharma’s Annual Report on Form 10-K for the year ended December 31, 2023, as well as other reports filed with the SEC including our most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2023. All of these documents are available on our website. Before making any decisions concerning our stock, you should read and understand those documents. We anticipate that subsequent events and developments will cause our views to change. We may choose to update these forward-looking statements at some point in the future, however, we disclaim any obligation to do so. As a result, you should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Investor & Media Contact: Lisa MillerLumos Pharma Investor Relations512-792-5454ir@lumos-pharma.com Source: Lumos Pharma, Inc.

临床2期孤儿药临床3期

2024-03-10

·药时代

Ferring首席科学家杨翼博士：肥胖症疫苗离我们还有多远？

正文共： 5928字 46图预计阅读时间： 15分钟目前在肥胖症市场上遥遥领先的诺和诺德，在新一代减肥药开发的意识形态领域也渴望引领潮流。在一代新药换旧药的领域，拾人牙慧的me-too做法对于大型制药公司来说是非常危险的。已经开创了GLP-1时代的诺和诺德已经开始酝酿新的头脑风暴，风暴的中心影影绰绰地闪现出“肥胖症疫苗”的概念。肥胖症疫苗是什么？What？虽然有人已经将semaglutide和tirzepatide这样的分子冠以“obesity vaccine”的头衔，但每周一次的给药频率显然配不上疫苗理念。Novo 首席科学官Marcus Schindler心目中的肥胖症疫苗是那种“一期一会，一年一针”，而且还要“达则兼济天下”地有利于心血管疾病管理的产品。诺和的头脑风暴并非空穴来风，肥胖症疫苗也并非没有先例，只是出师未捷身先死。诺和准备在波士顿的新基地进行RNA干扰疗法的开发，其中肥胖症药物将是研究的重点之一。肥胖症疫苗的使用人群也相对模糊，可以针对那些准备要进行体重管理的肥胖症患者，或者巩固减肥成果的“到彼岸”之人，抑或针对那些尚未罹患肥胖症的健康人群。不过可以确定的是，头脑中的肥胖症疫苗必须针对更深层次的代谢疾病的病理，而不是目前GLP-1药物这样抑制食欲的“水来土掩”的治标属性。雾里看花，究竟什么样的产品可称得上肥胖症疫苗？虽然诺和诺德没有给出明确的愿景和定义，但可以想象的是，肥胖症疫苗是一种预防或治疗肥胖症的生物制剂，通过激活机体的免疫系统或其他机制，调节体内的能量代谢、脂肪存储和食欲控制等生理过程，以减轻体重或预防肥胖症的发生。肥胖症疫苗可能包括传统意义上的疫苗，也可能包括其他类型的生物制剂或药物，其作用机制可能涉及免疫学、代谢调节、基因治疗等多个方面。肥胖症疫苗和目前的肥胖症GLP-1药物的区别可以表现在以下几个方面：01作用机制肥胖症疫苗：疫苗应该激发针对特定致病因素的免疫反应。所有疫苗都通过活性物质或抗原来发挥作用，触发免疫反应，产生中和抗体，结合抗原并将其从体内清除。抗原通常是蛋白质，但也可以是糖或脂质。肥胖症疫苗通常通过激活免疫系统或其他机制，调节体内的能量代谢、脂肪存储和食欲控制等生理过程，减轻体重或预防肥胖症的发生。这些疫苗可能影响身体的新陈代谢、脂肪细胞的分化和代谢、食欲调节等方面，从而实现减重的效果。治疗性肥胖症疫苗可以通过抑制食欲刺激激素和阻止营养吸收来治疗肥胖。胃、肠道、胰腺和脂肪组织的调节肽可以作为潜在的靶点进行疫苗开发。减肥药：减肥药通常通过影响身体的代谢、食欲或能量消耗等途径来减轻体重。减肥药可能通过抑制食欲、促进饱腹感、减少脂肪吸收或加速脂肪分解等方式发挥作用。02给药方式和频率肥胖症疫苗：肥胖症疫苗可能只需要接种一次或少数几次，就能够产生长期的保护效果，减少了给药的频率。诺和减肥疫苗的设想是每年给药一次。减肥药：减肥药通常需要经常性地服用，以维持其减重效果。这意味着患者需要定期服用药物，以保持体重的控制。例如目前的GLP-1药物Zepbound和Wegovy，注射给药频率都是每周一次。03治疗对象和目标人群肥胖症疫苗：肥胖症疫苗可能更适用于预防肥胖症的发生，或者用于那些有潜在风险但尚未患病的人群。它的目标是调节身体的新陈代谢和食欲，以防止肥胖的发生。当然也有治疗性疫苗针对已经发生肥胖症的患者。减肥药：减肥药通常用于已经患有肥胖症或体重超标的人群，用于治疗和控制病情。它的目标是帮助患者减轻体重，控制肥胖相关的健康风险。开发肥胖症疫苗的必要性Importance世界卫生组织官员警告说，尽管以GLP-1药物为代表的肥胖症药物有大行其道的趋势，但它们远远做不到“大辟天下寒士俱欢颜”的能力。这些药物无法解决目前影响超过 10 亿人的全球性肥胖症问题。2月29日，世卫组织发表了 2017 年以来首次全球肥胖症公开分析报告。该报告显示，自 1990 年以来，儿童和青少年的肥胖率增加了四倍，成年人的肥胖率增加了一倍多（图1），世界上大约每八个人中就有一人患有肥胖症。图1. 1990年以来全球肥胖症人群比例增长走势图。（数据来源：世卫组织、《柳叶刀》；图片来源：Bloomberg）虽然一些富裕国家（尤其是欧洲）的肥胖率已经趋于平稳，但研究小组发现低收入和中等收入国家的肥胖率迅速上升。研究小组在《柳叶刀》发表的一项研究中表示，营养不良导致的低体重问题已被肥胖取代，成为许多国家的主要问题。虽然诺和诺德和礼来的多肽减肥药可能将肥胖症市场推向2030年1000亿美元的高度，但它们同样可以加剧减肥药获取方面的社会不平等问题。研究显示，过去三十年美国成年人的肥胖率也大幅上升，男性肥胖率从 1990 年的 16.9% 暴涨至 2022 年的 41.6%。女性肥胖率则从 21.2% 升至 43.8%（图2）。图2. 美国肥胖症人群比例增长走势图。（数据来源：世卫组织、《柳叶刀》；图片来源：Bloomberg）在肥胖症已经成为全球性流行性疾病的大背景下，仅仅依靠产能极为不足的GLP-1药物来解决是不现实的。肥胖症疫苗的设想在这种环境下就显得非常有意义了，可以具体表现在以下几个方面：01预防性更强肥胖症疫苗可以在肥胖发生前提供预防性保护，与药物相比，它可能更具预防性。这意味着人们可以在患病前就开始接种疫苗，从而避免了后续的治疗和管理。02持久性保护一旦接种了肥胖症疫苗，它可能会提供长期的保护，而不需要像药物一样需要定期服用。这将减少患者的管理负担，并提高遵循治疗计划的可能性。03群体效益疫苗通常有助于建立群体免疫，即当大多数人都接种疫苗时，整个社区都会受益。这有助于减少肥胖症的传播，并降低整个社会的肥胖率。04预防并发症肥胖症是许多慢性疾病的风险因素，包括心血管疾病、糖尿病和某些癌症。通过预防肥胖，肥胖症疫苗可能会降低这些并发症的发生率。05经济效益预防肥胖症及其相关并发症可能会节省大量的医疗费用和资源。长期来看，这将对医疗系统和社会经济产生积极的影响。06降低医疗不平等在一些社会中，由于经济原因或其他社会因素，一些人群可能无法获得足够的医疗服务，这会导致医疗不平等。通过开发肥胖症疫苗并普及接种，可以降低因肥胖症而导致的医疗不平等，确保每个人都能获得适当的预防和治疗。肥胖症疫苗开发：西西弗斯的努力？Possibility of Success?肥胖症疫苗开发并不是新鲜事物，几乎二十年前就有了相关的临床研究，但没有能够获得成功。前度刘郎今又来，肥胖症疫苗的开发是否会像希腊神话中遭受惩罚的科林斯国王之子西西弗斯推动的那个巨石一样再次滑落到山谷？2005年，瑞士的一家小型生物技术公司Cytos biotechnology（目前已被Kuros Biosciences收购）就已经开始了肥胖症疫苗的开创性研究。它们的肥胖症疫苗资产CYT009-GhrQb 是一种针对肥胖症的治疗性疫苗。Cytos biotechnology将这款候选疫苗带入了I/II期临床研究。Cytos认为，这款疫苗不仅可以抑制食欲并有助于减肥，而且可以长期保持体重减轻。CYT009-GhrQb的潜在机理是帮助患者的免疫系统产生特定的抗饥饿素（anti-ghrelin）抗体。饥饿素（ghrelin）是一种肽激素，是一种主要由胃肠道（尤其是胃）分泌的肠激素，它会增加进食的动力。饥饿时，血液中饥饿素的水平增加，进餐后恢复到较低水平。饥饿素可能通过增加胃动力和刺激胃酸分泌来推动食物摄入的欲望。饥饿素可能是人类食物摄入和体重的关键调节剂。研究人员期望，接种 CYT009-GhrQb的患者体内会诱导产生抗饥饿素抗体，从而抑制或减少饥饿素进入大脑并发挥其活性。小鼠临床前实验表明，接种 CYT009-GhrQb 疫苗可诱导高水平的抗饥饿素特异性抗体。此外，在接受高脂肪饮食的小鼠中，接种疫苗后体重增加最多减少了15%。然而CYT009-GhrQb的I/II期临床试验没有获得成功，研究结果现实，它对显示它对受试者的体重或食物摄入量没有影响。CYT009-GhrQb临床失败的原因没有调查清楚。可能的解释是，要么产生的抗饥饿素抗体不足，要么中和人体循环的饥饿素本身就没有足够的效果来改变体重。而且还存在潜在的安全性问题。安进公司尝试了另一种删繁就简的方法，即直接注射单克隆抗饥饿素抗体。尽管观察到了一些急性效应，但由于缺乏对体重的长期影响，最终得出的结论是，使用抗体拮抗外周饥饿素肽并不能证明是治疗肥胖的有效方法。除了饥饿素之外，生长抑素（somatostatin）也成为了开发肥胖症疫苗的靶点。研究人员期待，抗生长抑素（anti-somatostatin）疫苗可以消除生长抑素对于生长激素（GH）和 IGF-1 （胰岛素样生长因子）分泌的抑制作用，从而缓解与这些激素低水平相关的肥胖。Braasch Biotech LLC在小鼠上测试了疫苗接种效果。接种疫苗的小鼠体重下降了 10%（在对照小鼠中未见）。研究结果表明，疫苗能诱导生长抑素抗体，并显著减轻小鼠体重。然而并没有关于抗生长抑素疫苗进入肥胖症临床研究的相关报道。除了饥饿素和生长抑素之外，肥胖症疫苗开发过程中针对的靶点还有GIP，脂肪组织抗原和腺病毒等，但都没有最终取得正果。展望未来Perspective肥胖症疫苗的开发前景令人充满期待。随着对肥胖症发病机制的深入研究，科学家们正不断发现肥胖症与免疫系统、代谢过程以及肠道微生物群等之间复杂而密切的关系。这些发现为疫苗的研发提供了新的思路和方向。一些早期的实验和临床研究已经展示了一些潜在的疫苗候选物，这些疫苗可以通过激活免疫系统，促进脂肪代谢，抑制脂肪细胞的增殖和脂肪堆积，从而达到减轻肥胖症的效果。虽然目前这些候选疫苗仍处于早期阶段，并需要进一步的研究和验证，但这些积极的结果为肥胖症疫苗的开发提供了希望。随着基因工程、生物技术和疫苗制造技术的不断进步，肥胖症疫苗的研发将变得更加高效和精确。未来，可能会出现针对不同人群和不同病因的个性化疫苗，从而更好地满足不同患者的需求。此外，随着社会对健康意识的提高和健康预防的重视，肥胖症疫苗的市场需求也将逐渐增加。政府、医疗机构和生物制药公司等各方都将加大对肥胖症疫苗研发的支持和投入，从而加速疫苗的研发进程，并最终实现肥胖症的有效预防和控制。综上所述，肥胖症疫苗的开发前景充满希望。尽管仍需面对诸多挑战，但随着科学技术的不断进步和社会对健康的关注度的提高，相信肥胖症疫苗将成为未来预防和管理肥胖症的重要手段，为全球健康事业带来新的突破和进步。杨翼博士分别于1999年和2002年获得南开大学化学学士与硕士学位，后在德国著名多肽化学家Nobert Sewald 教授指导下进行多肽合成与结构研究，并于2008年获得德国比勒菲尔德大学博士学位。之后就职于位于瑞士Visp 的Lonza AG，负责多肽API的工业开发，优化，以及GMP生产。目前在丹麦哥本哈根Ferring Pharmaceutical A/S担任首席科学家，领导多肽药物合成的研发与GMP生产。杨翼博士在多肽化学，副反应与杂质研究，工艺研发与优化，GMP生产，包括遗传毒性杂质的分析与控制，工业生产风险评估，Quality-by-Design等领域具有丰富的经验。拥有Lean-Six-Sigma 黑带认证，发表诸多学术论文，并著有学术专著“Side Reactions in Peptide Synthesis”（Academic Press, 2015）。 Reference：Chen, E. A ‘vaccine-like’ version of Wegovy is on the drawing board at Novo Nordisk. STAT. 29. 02. 2024.Kresge, N. et al. Obesity Drugs Won’t Fix a Billion-Person Problem, WHO Warns. Bloomberg. 01. 03. 2024.Hanlon, M. Obesity vaccine enters clinical trial. New Atlas. 19. 05. 2005.Lu, S. C. et al. An acyl-ghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol Pharmacol, 2009. 75, 901-907.Patterson, M. et al. Ghrelin and appetite control in humans—Potential application in the treatment of obesity. Peptides. 2011. 32, 2290-2294.Mueller, T. D. et al. Anti-obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery. 2022. 21, 201–223.Overweight? There's a vaccine for that, at least for mice. BioMed Central Limited. 09. 07. 2012. Bays, H. E. et al. Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. Obesity Pillars. 2022. 2, 100018.封面图来源：123rf版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn礼来D药推迟上市，FDA的B面下一代GLP-1类药物早期临床数据读出，直接推动诺和诺德成为6000亿美元市值药企！美中数据跨境新政对医药行业的影响及应对【完整会议日程】大咖云集，干货满满，一场盛会如约而至！超15亿美元！吉利德权益锁定三特异性抗体肿瘤药当年利拉鲁肽没做到的，让司美格鲁肽实现了？这种疾病的治疗方案可能出现大变化！点击这里，欣赏更多精彩内容！

疫苗

2023-07-13

·GlobeNewswire-Health Care

Aeterna Zentaris Outlines Progress on Development Pipeline Programs and Provides Corporate Update

Highlights progress, recent developments and upcoming key milestonesCompany continues to build growing body of data across pipeline, advancing towards first in human studiesStrong financial position with cash projected to fund operations and advancement of priority pipeline programs into 2025 TORONTO, ONTARIO, July 13, 2023 (GLOBE NEWSWIRE) -- Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) (“Aeterna” or the “Company”), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products, today provided an update on its therapeutic and diagnostic development pipeline programs and outlined upcoming key milestones. “We are encouraged by our significant progress across all of our active development programs, and based on the prioritization of our pipeline, have strengthened our focus on our diagnostic and therapeutic programs as we execute on key decision points,” commented Dr. Klaus Paulini, Chief Executive Officer of Aeterna. “Additionally, in our ongoing DETECT clinical trial, we are making significant progress regarding patient recruitment and believe we are well-positioned to continue building momentum towards completion of the study by year’s end. Further, based upon our active outreach and discussions, we expect to secure an alternate development and commercialization partner for Macrilen® for the U.S. and Canada.” Therapeutics Development Pipeline Update Autoimmunity Modifying ("AIM") Biologicals: Targeted, highly specific autoimmunity modifying fusion proteins for the potential treatment of neuromyelitis optica spectrum disorder ("NMOSD") and Parkinson's disease (“PD”) AIM Biologicals represent a unique platform technology with the potential to address the cause and not only the symptoms of auto-immune and inflammatory, neurodegenerative disorders at early stages. This approach is based on induction of selective and highly target-specific immune de-sensibilization based on the natural concept of feto-maternal tolerance. Dr. Paulini added, “We have received encouraging feedback from our collaborator and scientific advisor on the NMOSD indication, Dr. Michael Levy, Research Director of the Division of Neuroimmunology & Neuroinfectious Disease at Massachusetts General Hospital. Dr. Levy shares our vision that presenting antigens on soluble HLA-G fusion proteins is a promising, novel approach to induce antigen specific immune tolerance among NMOSD and PD patients. Together, we look forward to furthering the development of this program.” Recent Highlights Demonstrated positive pre-clinical proof-of-concept in various in-vitro and in-vivo models.In-depth profiling of a limited set of candidates for potential use in clinical development.Confirmed AIM Biologicals’ mechanism of action and efficacy in ex-vivo studies in human blood samples from both NMOSD and PD patients. Next Steps Evaluation of manufacturing strategy and initiation of production of selected development candidates.Ongoing compilation of a comprehensive pre-clinical data package for scientific advice meetings with regulatory authorities, expected to take place in the near future. Delayed Clearance Parathyroid Hormone ("DC-PTH", AEZS-150) Fusion Proteins: Potential treatment for chronic hypoparathyroidism AEZS-150 is a fusion protein of PTH [1-34] coupled to a modified human growth-hormone binding protein (GHBP). Preclinical results so far indicate the potential for maintaining regular calcium and phosphate levels in blood longer and more consistently than with current treatments. This project aims to address this debilitating orphan disease, which is currently without satisfactory treatment options, with weekly instead of daily injections. “There is a major unmet need for physiological parathyroid hormone replacement in patients with hypoparathyroidism, either congenital or acquired from neck surgery, who have an impaired quality of life and increased morbidity and mortality on current therapy. DC-PTH will address this unmet need,” commented Prof. Richard Ross, MD, FRCP, Department of Oncology and Metabolism at Sheffield University (UK). “Aeterna has made great progress in the manufacturing process development of AEZS-150 and repeating validation studies in models of hypoparathyroidism required before undertaking trials in patients.” Recent Highlights Detailed profiling of AEZS-150 through in-vitro studies and in-vivo models of hypoparathyroidism.Established a master cell bank for a cell line expressing AEZS-150 in good yield.Continued progress in the development of a production process suitable for larger scale GMP manufacturing. Next Steps Meet with regulatory authorities to determine the development path forward; Company expects such a meeting in Q4/2023, and as outcome, an abbreviated safety and toxicology program as the active principle ([1-34]-PTH fragment) is already approved and in use.Initiate IND-enabling preclinical studies in 2024. Macimorelin Therapeutic (AEZS-130): Ghrelin agonist in development for the treatment of ALS (Lou Gehrig's disease) Amyotrophic Lateral Sclerosis (ALS) is a debilitating and deadly orphan disease, and those who suffer from this terminal condition have few treatment options. Macimorelin’s (AEZS-130) multiple modes of action should have the potential to improve the quality of life for these patients. Recent Highlights Successful development of an alternative formulation suitable for use in ALS.Accumulating data for positive effects of AEZS-130 treatment on survival of motor-neurons.Continued assessment of AEZS-130 in transgenic mouse ALS models and in human patient-derived neuron cultures.Completion of initial toxicology and safety studies to support clinical development as a therapeutic, in addition to the already existing body of safety and toxicology data from our macimorelin diagnostic development. Next Steps Following achievement of proof-of-concept, the Company will seek to have a scientific advice meeting with regulatory authorities to discuss program development next steps.Completion of toxicology and safety studies to support treatment over prolonged periods. Diagnostics Development and Commercialization Update Macimorelin Diagnostic: Approved and commercialized as test for adult growth hormone deficiency and in clinical Phase 3 development for childhood-onset growth hormone deficiency ("CGHD") testing. Aeterna is currently conducting its pivotal Phase 3 safety and efficacy study AEZS-130-P02 (the “DETECT-trial”) evaluating macimorelin for the diagnosis of Childhood Onset Growth Hormone Deficiency (“CGHD”). Most clinical sites in the U.S. as well as European countries are open for patient recruitment. Recent Highlights Phase 3 Study: Significant progress made with DETECT patient recruitment also by engagement of an additional Clinical Research Organization (CRO). Currently three new countries (Armenia, Slovakia, and Turkey), have ongoing DETECT clinical trial application activities and almost half the foreseen subjects have meanwhile concluded the trial.Macimorelin Commercialization: Having regained full rights to Macrilen® for the U.S. and Canada from Novo Nordisk in May 2023, the Company is actively focused on identifying an alternate development and commercialization partner for Macrilen® for U.S. and Canada. “We continue to manage our cash responsibly with a balanced de-risked development approach, which we believe enables us to optimize the Company's capital and human resources,” added Giuliano La Fratta, Chief Financial Officer of Aeterna. “We remain focused on advancing our programs to their next phase of development, guided by the data and financial risk/reward as we do so. Based on our current projections, we believe the Company has the ability to meet its currently anticipated cash needs into 2025.” About Aeterna Zentaris Inc. Aeterna Zentaris is a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products focused on areas of significant unmet medical need. The Company's lead product, macimorelin (Macrilen®; Ghryvelin™), is the first and only U.S. FDA and European Commission approved oral test indicated for the diagnosis of adult growth hormone deficiency (AGHD). The Company is leveraging the clinical success and compelling safety profile of macimorelin to develop it for the diagnosis of childhood-onset growth hormone deficiency (CGHD), an area of significant unmet need. Aeterna Zentaris is dedicated to the development of its therapeutic asset and has established a pre-clinical development pipeline to potentially address unmet medical needs across a number of indications, including neuromyelitis optica spectrum disorder (NMOSD), Parkinson's disease (PD), hypoparathyroidism and amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease). For more information, please visit www.zentaris.com and connect with the Company on Twitter, LinkedIn and Facebook. Forward-Looking Statements This press release contains statements that may constitute forward-looking statements within the meaning of U.S. and Canadian securities legislation and regulations, and such statements are made pursuant to the safe-harbor provision of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements are frequently, but not always, identified by words such as "expects," "aiming", "anticipates," "believes," "intends," "potential," "possible," and similar expressions. Such statements, based as they are on current expectations of management, inherently involve numerous risks, uncertainty and assumptions, known and unknown, many of which are beyond our control. Forward-looking statements in this press release include, but are not limited to, those relating to Aeterna's expectations regarding: its preclinical and clinical studies, its ability to secure regulatory approvals for Macrilen™, its efforts to obtain a development and commercialization partner for Macrilen™ in the U.S. and Canada and the ability to meet its currently anticipated cash needs into 2025. Forward-looking statements involve known and unknown risks and uncertainties, and other factors which may cause the actual results, performance or achievements stated herein to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information. Such risks and uncertainties include, among others, our reliance on the success of the DETECT clinical trial in the European Union and U.S. for Macrilen™ (macimorelin) in CGHD; results from our ongoing or planned pre-clinical studies and our DETECT clinical trial under development may not be successful or may not support advancing the product further in pre-clinical studies, to human clinical trials or regulatory approval; our ability to raise capital and obtain financing to continue our currently planned operations; our now heavy dependence on the success of Macrilen™ (macimorelin) and related out-licensing arrangements and the continued availability of funds and resources to successfully commercialize the product; the global instability due to the global pandemic of COVID-19 and the war in the Ukraine, and their unknown potential effect on our planned operations; our ability to enter into out-licensing, development, manufacturing, marketing and distribution agreements with other pharmaceutical companies and keep such agreements in effect; and our ability to continue to list our common shares on the NASDAQ. Investors should consult our quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties, including those risks discussed in our Annual Report on Form 20-F and annual information form, under the caption "Risk Factors". Given the uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law. No securities regulatory authority has either approved or disapproved of the contents of this news release. The Toronto Stock Exchange accepts no responsibility for the adequacy or accuracy of this release. Investor Contact: Jenene ThomasJTC TeamT (US): +1 (833) 475-8247E: aezs@jtcir.com

临床3期

100 项与合成生长素相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	合成生长素	-	DB11895

研发状态

适应症	最高研发状态	国家/地区	公司
脑震荡	临床2期	美国更多	Oxeia Biopharmaceuticals, Inc.初创企业更多
恶病质	终止	美国更多	Asubio Pharma Co. Ltd. 更多
神经性厌食症	终止	日本更多	Asubio Pharma Co. Ltd. 更多
肌肉萎缩	终止	日本更多	KineMed, Inc. 更多

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01898611 (CTgov)	临床2期	虚弱综合症	16	Ghrelin (Ghrelin Plus Resistance Training)	(顧窪選獵獵糧齋艱憲選) = 衊淵壓廠襯壓蓋積襯艱積積觸遞積獵獵獵構憲 (網選積齋構鹹憲膚窪築, 網鹽築憲鬱蓋蓋願範鹹 ~ 壓淵餘憲廠鹹鹹夢繭壓) 更多	-	2018-10-11
				Placebo (Placebo Plus Resistance Training)	(顧窪選獵獵糧齋艱憲選) = 膚構鏇鑰膚鹽鏇鏇餘窪積積觸遞積獵獵獵構憲 (網選積齋構鹹憲膚窪築, 膚膚觸艱鹹觸餘艱壓鬱 ~ 夢衊鏇廠膚餘膚網獵簾) 更多
Pubmed \| Med J Aust	N/A	肿瘤 \| 恶病质 \| 厌食症	-	Ghrelin (2 microg kg(-1))	觸繭衊鏇範憲蓋觸獵膚(衊遞簾繭蓋觸遞壓衊窪) = 蓋範選淵艱製簾醖膚夢膚衊繭憲獵鹽獵襯餘製 (製窪艱膚網顧窪範製築 )	-	2008-01-29
				Ghrelin (8 microg kg(-1))	觸繭衊鏇範憲蓋觸獵膚(衊遞簾繭蓋觸遞壓衊窪) = 觸齋淵積鹽蓋積憲遞鑰膚衊繭憲獵鹽獵襯餘製 (製窪艱膚網顧窪範製築 )
NCT04558346 (Corporate Publications) 人工标引	临床2期	脑震荡	-	OXE103	網廠製構鏇願鬱觸顧鑰(築齋膚壓鹽築網廠製獵) = Promising interim results show potential for OXE103 as an effective treatment for concussion 願醖鬱襯襯願築廠鹽繭 (構簾積繭築蓋窪積鬱鏇 )	积极	2022-08-03
NCT01190085 (CTgov)	N/A	酗酒	45	Ghrelin (Ghrelin (1 Microg/kg))	糧齋醖夢廠壓構選鬱廠(鹽襯鹽鑰壓鏇積願醖糧) = 繭蓋鑰襯獵選選夢壓廠壓鏇糧壓蓋鏇製膚憲衊 (鹹觸齋鬱醖鏇願醖糧夢, 築範築醖衊艱築壓繭糧 ~ 鹽齋獵製顧廠衊膚構窪) 更多	-	2014-04-29
				Ghrelin (Ghrelin (3 Microg/kg))	糧齋醖夢廠壓構選鬱廠(鹽襯鹽鑰壓鏇積願醖糧) = 蓋壓餘襯膚淵鹹鬱觸窪壓鏇糧壓蓋鏇製膚憲衊 (鹹觸齋鬱醖鏇願醖糧夢, 壓蓋築廠鏇觸築鏇夢鹽 ~ 繭遞廠鬱衊選顧鹽築鏇) 更多
ADA2022	N/A	-	9	Acyl-ghrelin	壓鑰簾觸襯鏇構願構鬱(壓觸壓齋繭範蓋獵築餘) = 齋選製網網窪壓膚範鬱艱顧鏇構鏇醖糧鑰壓壓 (襯夢簾積簾鬱艱築繭網 )	-	2022-06-01
				Placebo	壓鑰簾觸襯鏇構願構鬱(壓觸壓齋繭範蓋獵築餘) = 鏇鏇窪衊壓艱範壓築鏇艱顧鏇構鏇醖糧鑰壓壓 (襯夢簾積簾鬱艱築繭網 )
NCT00698828 (CTgov)	临床2期	恶病质 \| 慢性阻塞性肺疾病	227	placebo+SUN11031 (Placebo)	襯淵齋夢鏇夢鏇糧廠製(齋衊壓積淵鹹繭鹹窪鹽) = 窪構憲遞選鹽壓廠鏇製繭簾簾繭範鹹窪憲襯醖 (餘製糧醖鬱廠廠築糧艱, 醖鹹選夢淵願糧顧範糧 ~ 壓鹽選顧顧艱鬱鬱夢網) 更多	-	2021-01-28
				SUN11031 (SUN11031 20 μg/kg)	襯淵齋夢鏇夢鏇糧廠製(齋衊壓積淵鹹繭鹹窪鹽) = 膚齋衊範憲襯築壓繭築繭簾簾繭範鹹窪憲襯醖 (餘製糧醖鬱廠廠築糧艱, 鬱淵鑰鹹選壓網憲窪夢 ~ 艱齋積鬱繭製衊膚選餘) 更多