A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose Ranging Study to Evaluate the Efficacy and Safety of Prosaptide Over 6 Weeks of Treatment for the Relief of Neuropathic Pain Associated With HIV-1

This is a double-blind, placebo-controlled, parallel groups study to determine whether prosptide is effective in relieving pain in patients who have sensory neuropathic pain related to their HIV infection or the drugs used to treat it.

开始日期2003-09-01

申办/合作机构

Savient Pharmaceuticals, Inc.

100 项与 Prosaptide TX14 A 相关的临床结果

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100 项与 Prosaptide TX14 A 相关的转化医学

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100 项与 Prosaptide TX14 A 相关的专利（医药）

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103

项与 Prosaptide TX14 A 相关的文献（医药）

2024-09-01·ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

Ambient air pollution decreased normal fertilization rate via the mediation of seminal prosaposin

Article

作者: Liu, Lanlan ; Pan, Luxiang ; Cai, Jiali ; Ren, Jianzhi ; Jiang, Xiaoming ; Chen, Kaijie ; Liu, Zhenfang ; Gao, Peng

OBJECTIVE:

This study focuses on the association between seminal concentration of prosaposin and ambient air pollutants and whether the association affects the normal fertilization rate in vitro fertilization (IVF) treatment.

METHODS:

The cohort of 323 couple participants aged 22-46 was recruited from Jan. 2013 to Jun. 2018. At enrollment, resident address information was obtained and semen parameters of male counterparts were evaluated according to WHO criteria. We used inverse distance weighting interpolation to estimate the levels of ambient pollutants (SO₂, O₃, CO, NO₂, PM_2.5, and PM₁₀) in the surrounding area. The exposure of each participant was estimated based on the data gathered from air quality monitoring stations and their home address over various periods (0-9, 10-14, and 0-90 days) before semen sampling. The generalized linear regression model (GLM) and the Bayesian kernel machine regression (BKMR) were used to analyze the associations between pollutants, semen parameters, prosaposin, and normal fertilization. Additionally, the mediating effect of prosaposin and semen parameters on the link between pollutants and normal fertilization was investigated.

RESULTS:

GLM and BKMR showed exposure to ambient air pollutants was all associated with the concentration of seminal prosaposin, among them, O₃ and CO were also associated with normal fertilization (-0.10, 95 %CI: -0.13, -0.06; -26.43, 95 %CI: -33.79, -19.07). Among the semen parameters, only the concentration of prosaposin and total motile sperm count (TMC) was associated with normal fertilization (0.059, 95 %CI: 0.047, 0.071; 0.016, 95 %CI: 0.012, 0.020). Mediation analysis showed that prosaposin played a stronger mediating role than TMC in the relationship between short-term exposure to O₃ and fertilization (66.83 %, P<0.001 versus 3.05 %, P>0.05).

CONCLUSION:

Seminal plasma prosaposin showed a stronger meditating effect reflect the correlation between ambient air pollutants and normal fertilization rate than conventional semen parameters, which may be used as one of the indicators between pollution and fertilization in IVF.

2024-06-01·Tissue & cell

Selective prosaposin expression in Langerhans islets of the mouse pancreas

Article

作者: Sohel, Md Shahriar Hasan ; Saito, Shouichiro ; Fuyuki, Aimi ; Homma, Takeshi ; Onouchi, Sawa ; Takashima, Shigeo ; Kitamura, Kai

The islets of Langerhans are clusters of endocrine cells surrounded by exocrine acinar cells in the pancreas. Prosaposin is a housekeeping protein required for normal lysosomal function, but its expression level is significantly different among tissues. Prosaposin also exists in various body fluids including serum. Intracellularly, prosaposin activates lysosomes and may support autophagy, and extracellularly, prosaposin promotes survival of neurons via G protein-coupled receptors. In this study, prosaposin and its mRNA expression were examined in endocrine cells of the islets as well as in exocrine acinar cells in the pancreas of mice by in situ hybridization and immunostaining. High expression levels of prosaposin were found in Alpha, Beta and Delta cells in the islets, whereas prosaposin mRNA expression was faint or negative and prosaposin immunoreactivity was negative in exocrine acinar cells. The high expression levels of prosaposin in endocrine cells may indicate that prosaposin plays a crucial role in crinophagy, which is a characteristic autophagy in peptide-secreting endocrine cells, and/or that prosaposin is secreted from pancreatic islets. Since prosaposin has been reported in serum, this study suggests a new possible function of the Langerhans islets.

2024-01-01·Journal of clinical biochemistry and nutrition

Prosaposin is a novel coenzyme Q10-binding protein

Article

作者: Yamamoto, Yorihiro ; Hasegawa, Makoto ; Fujisawa, Akio ; Kashiba, Misato

Coenzyme Q10 (CoQ10) is essential for mitochondrial ATP production and functions as an important antioxidant in every biomembrane and lipoprotein. Due to its hydrophobicity, a binding and transfer protein for CoQ10 is plausible, and we previously described saposin B as a CoQ10-binding and transfer protein. Here, we report that prosaposin, the precursor of saposin B, also binds CoQ10. As prosaposin is both a secretory protein and integral membrane protein, it is ubiquitous in the body. Prosaposin was isolated from human seminal plasma, and CoQ10 was extracted from hexane solution into the water phase. It was additionally found that immunoprecipitates of mouse brain cytosol generated using two different anti-prosaposin antibodies contained coenzyme Q9. Furthermore, mouse liver cytosol and mouse kidney cytosol also contained prosaposin-coenzyme Q9 complex. These results suggest that prosaposin binds CoQ10 in human cells and body fluids. The significance and role of the Psap-CoQ10 complex in vivo is also discussed.

项与 Prosaptide TX14 A 相关的新闻（医药）

2024-02-23

·生物谷

Science：新方法重新暴露癌症抗原以增强肿瘤免疫疗法

肿瘤组织中含有大量垂死细胞，它们会脱落含有肿瘤抗原的小囊泡。称为树突细胞的免疫细胞会摄取这些囊泡，处理抗原，并在其表面呈递抗原碎片，从而教会T细胞识别和攻击这些抗原。成功的癌症免疫疗法涉及激活患者自身的 T 细胞，以识别肿瘤表面上称为抗原的特征性蛋白并对其进行攻击。但有些肿瘤有一个诀窍：它们通过阻止其抗原的显示来躲避免疫系统的攻击。在一项新的研究中，来自美国哈佛医学院等研究机构的研究人员在小鼠身上找到了绕过这种防御的方法。他们指出其中的关键在于一种名为prosaposin的蛋白。这些发现为开发附加疗法提供了一种策略，从而使癌症免疫疗法更加有效。相关研究结果近期发表在Science期刊上，论文标题为“Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape”。肿瘤组织中含有大量垂死细胞，它们会脱落含有肿瘤抗原的小囊泡。称为树突细胞的免疫细胞会摄取这些囊泡，处理抗原，并在其表面呈递抗原碎片，从而教会T细胞识别和攻击这些抗原。这些作者发现，如果没有prosaposin，树突细胞就无法分解囊泡，并将肿瘤抗原作为一种教学工具呈递给免疫系统。具体来说，他们发现树突细胞需要一种叫做saposins的蛋白，而saposins由prosaposin形成。论文通讯作者作者、波士顿儿童医院细胞与分子医学项目儿科副教授Florian Winau解释说，“我们发现，要消化这些囊泡并将肿瘤抗原释放出来以呈递给免疫系统，就需要saposins。” 让肿瘤抗原无所遁形 Winau及其同事们发现，肿瘤通过在prosaposin中加入糖分子链，使其抗原无法被免疫系统识别。这使得树突细胞分泌prosaposin，耗尽了它们的saposins供应。这样，树突细胞就无法消化囊泡，并释放出里面的肿瘤抗原。这些作者的下一步是尝试重新添加prosaposin。在皮肤癌黑色素瘤的小鼠模型中，他们给这些小鼠静脉注射了一种靶向树突细胞的抗体。这种疗法使得它们的免疫系统再次检测到肿瘤抗原并激活 T 细胞。图片来自Science, 2024, doi:10.1126/science.adg1955 当这些作者将prosaposin与免疫检查点抑制剂药物结合使用时，他们发现肿瘤生长有所减少。不过要确认基于prosaposin的治疗是否对人类有效，还需要进一步的研究。 Winau及其同事们已经申请了这项技术的专利。他们与一家行业合作伙伴合作，设计了一种靶向系统来递送prosaposin，并希望开发出一种候选药物，在人体临床试验中进行测试。在另一个项目中，他们正在开发一种诊断测试，用于检测人体血液中糖分子链修饰的prosaposin。他们的目标指出当患者的肿瘤抗原呈递受损、肿瘤正在逃避免疫攻击时，需要改变治疗。（生物谷 Bioon.com）参考资料： Pankaj Sharma et al. Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape. Science, 2024, doi:10.1126/science.adg1955. Re-exposing a cancer protein to enhance immunotherapyhttps://medicalxpress.com/news/2024-02-exposing-cancer-protein-immunotherapy.html

免疫疗法

2023-04-27

·生物谷

Nat Commun：揭示PRSS2通过抑制Tsp-1重塑肿瘤微环境，从而刺激肿瘤生长和进展

胰腺癌是致命的，而且难以治疗，部分原因是它们经常在晚期被发现；这种癌症的总体五年生存率约为11%。在一项新的研究中，来自美国波士顿儿童医院的研究人员对这种难治性癌症采用了不同寻常的方法，并且发现了一些胰腺癌是致命的，而且难以治疗，部分原因是它们经常在晚期被发现；这种癌症的总体五年生存率约为11%。在一项新的研究中，来自美国波士顿儿童医院的研究人员对这种难治性癌症采用了不同寻常的方法，并且发现了一些非常有希望的线索。相关研究结果近期发表在Nature Communications期刊上，论文标题为“PRSS2 remodels the tumor microenvironment via repression of Tsp1 to stimulate tumor growth and progression”。论文通讯作者、波士顿儿童医院血管生物学项目研究员Randolph Watnick博士首先发现作为一种治疗多种癌症的新兴方法，免疫疗法在胰腺癌中基本上是失败的，因为肿瘤微环境分泌了多种阻碍免疫反应的因子。 Watnick团队先前已发现一种天然存在的蛋白---血小板反应蛋白-1（thrombospondin-1, Tsp-1）---强烈抑制了多种肿瘤的生长。他们还表发现一种名为prosaposin的化合物以及由其衍生的化合物可以刺激Tsp-1，从而阻止肿瘤的生长。但是，胰腺肿瘤很聪明：它们分泌一种叫做PRSS2的分子来抑制Tsp-1。在不存在Tsp-1的情形下，肿瘤微环境就会采取一系列防御措施，阻止免疫系统遏制癌症的发生。Watnick说，“这些细胞分泌了许多杀死或抑制免疫细胞激活的因子，很难将全部靶向它们。肿瘤可在以不惧怕免疫系统的情形下生长。” 但是当Watnick团队在人类癌症细胞系和小鼠中阻断PRSS2时，他们恢复了Tsp-1的表达，一举使肿瘤的许多防御功能失效。这使得免疫系统能够抑制肿瘤的生长。更令人兴奋的是，PRSS2在血液中循环，使得它成为抗体靶向的理想候选对象。而且，由于它通常不会发生突变（它只是被肿瘤细胞过量表达），癌症不太可能对治疗产生抵抗性。Watnick说，这项新研究中描述的这种方法可能也适用于卵巢癌和三阴性乳腺癌，它们有类似的自我保护策略。髓系细胞特异性的LRP1缺失通过阻止Tsp-1的抑制来阻止肿瘤生长。图片来自Nature Communications, 2022, doi:10.1038/s41467-022-35649-9。他说，“如果我们能制造出针对PRSS2的抗体，它有可能成为患者的新生命线。”他的实验室如今正在努力开发一种抗体，并正在考虑将它与prosaposin和/或PD1抑制剂等免疫疗法相结合的策略。让胰腺肿瘤挨饿此外，波士顿儿童医院内分泌科研究员Nada Kalaany博士及其研究团队采取了一种完全不同的方法，提出了一个问题：“胰腺肿瘤需要什么来生长？”她专注于胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）。PDAC是一种侵袭性的癌症，依靠不寻常的代谢途径来获得营养物。为了支持它们的生长，胰腺肿瘤必须制造大量的称为多胺（polyamine）的化合物。Kalaany团队发现这种癌症的肿瘤微环境缺乏一种关键成分---精氨酸（arginine），从而迫使这种肿瘤求助于另一种代谢途径（Nature, 2023, doi:10.1038/s41586-023-05891-2）。这种主要用于婴儿期和禁食的成人肠道中的代谢途径需要一种称为鸟氨酸转氨酶（ornithine aminotransferase, OAT）的酶。 Kalaany解释说，“这种癌症通过使用OAT制造多胺来克服具有挑战性的、精氨酸匮乏的肿瘤微环境。如果我们靶向OAT，那么我们可以抑制肿瘤生长。” 事实上，当Kalaany团队用一种叫做5-FMO的药物抑制OAT时，他们在培养皿中和小鼠模型中都抑制了癌症生长。这一发现为胰腺癌的治疗增加了另一种潜在的选择。靶向OAT可以避免毒副作用，因为正常的胰腺细胞不需要OAT来制造多胺。由于5-FMO已被实验用于其他目的，Kalaany认为将这些发现转化为临床的潜力很大。 Kalaany说，“癌症总能找到规避的方法。但是，如果我们靶向这一途径，它们可能就没有办法绕过它。” （生物谷 Bioon.com）参考资料： 1. Lufei Sui et al. PRSS2 remodels the tumor microenvironment via repression of Tsp1 to stimulate tumor growth and progression. Nature Communications, 2022, doi:10.1038/s41467-022-35649-9. 2. How the tumor microenvironment stimulates pancreatic cancer growth and progressionhttps://medicalxpress.com/news/2023-04-tumor-microenvironment-pancreatic-cancer-growth.html

免疫疗法临床2期

100 项与 Prosaptide TX14 A 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
HIV血清阳性	临床2期	-	Savient Pharmaceuticals, Inc.	2003-09-01
神经痛	临床2期	-	Savient Pharmaceuticals, Inc.	2003-09-01
糖尿病性神经病变	临床2期	美国	-	-
糖尿病性神经病变	临床2期	-	Savient Pharmaceuticals, Inc.	-