更新于：2024-05-01

CD49d

整合素-4

更新于：2024-05-01

基本信息

别名

整合素α4、alpha 4 subunit of VLA-4 receptor、antigen CD49D

+ [8]

简介

Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877).

关联

那他珠单抗生物类似药 (Polpharma Biologics)

靶点

CD49d

作用机制

CD49d拮抗剂

在研机构

Sandoz, Inc. [+2]

原研机构

Polpharma Biologics S.A.

在研适应症

复发-缓解型多发性硬化 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2023-08-24

Natalizumab

那他珠单抗

靶点

CD49d

作用机制

CD49d拮抗剂

在研机构

Biogen Netherlands BV [+1]

原研机构

Biogen, Inc.

在研适应症

克罗恩病 [+2]

非在研适应症

急性移植物抗宿主病 [+15]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2004-11-23

AXR-159

靶点

CD49d

作用机制

CD49d拮抗剂

在研机构

AxeroVision, Inc.

原研机构

AxeroVision, Inc.

在研适应症

干眼症

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

138

项与 CD49d 相关的临床试验

NCT03811886 / Recruiting临床1/2期

A Phase I/II Study of Natalizumab as a Single Agent in Children, Adolescents and Young Adults With Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma

The purpose of this study is to evaluate the safety and tolerability of Natalizumab in children, adolescent and young adult patients with pulmonary metastatic osteosarcoma (pOS) and to assess clinical response associated with this treatment as well as overall survival.

开始日期2024-06-01

申办/合作机构

The Case Comprehensive Cancer Center

NCT05658497 / RecruitingN/A

Vumerity (Diroximel Fumarate) Prospective MS Pregnancy Exposure Registry

The primary objectives of the study are to estimate the risk of major congenital malformations (MCMs) in infants born to women with multiple sclerosis (MS) who were exposed to diroximel fumarate (DRF) at any time from 2 weeks after the first day of their last menstrual period (LMP) up through the first trimester of pregnancy and to comparatively evaluate pregnancy outcomes with MCMs in women with MS who were exposed to DRF at any time from 2 weeks after the first day of their LMP through the first trimester of pregnancy with the following: i) women with MS who were unexposed to disease modifying therapies (DMTs) and, ii) women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries).
The secondary objective of the study is to evaluate pregnancy outcomes in women with DRF exposure at any time from 2 weeks after the first day of their LMP through the end of pregnancy compared with the following: i) women with MS who were unexposed to DMTs, ii) women with dimethyl fumarate (DMF) exposure, iii) women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries), and iv) women without MS (e.g., women from external, general population comparators).

开始日期2023-10-27

申办/合作机构

Biogen, Inc.

NCT05618301 / Recruiting临床1期IIT

A Pilot Safety and Feasibility Study to Evaluate Motixafortide (CXCR4/SDF-1 Inhibition) and Natalizumab (VLA-4/VCAM-1 Inhibition) as a Novel Regimen to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)

Hematopoietic stem cell (HSC)-based gene therapies now offer curative potential for patients with sickle cell disease (SCD), with decreased toxicity compared to allogeneic hematopoietic cell transplantation. However, effective HSC-based gene therapy depends on collecting sufficient HSCs to generate the therapeutic product, and currently available mobilization regimens carry unacceptable risk for patients with SCD or do not reliably yield optimal numbers of HSCs for gene therapy.
The investigators hypothesize that HSC mobilization with motixafortide (CXCR4i) alone and the combination of motixafortide plus natalizumab (VLA-4i) will be safe and tolerable in SCD patients. In addition, the investigators hypothesize that combined CXCR4 and VLA-4 blockade with motixafortide plus natalizumab will result in a rapid, robust, and synergistic increase in HSC mobilization to peripheral blood (PB) in patients with SCD, when compared to motixafortide alone.

开始日期2023-07-07

申办/合作机构

Washington University School of Medicine

[+2]

100 项与 CD49d 相关的临床结果

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100 项与 CD49d 相关的转化医学

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0 项与 CD49d 相关的专利（医药）

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2,304

项与 CD49d 相关的文献（医药）

2024-02-22·JCI insight

Rapamycin rescues loss-of-function in blood-brain barrier-interacting regulatory T cells.

Article

作者: Paulien Baeten ; Ibrahim Hamad ; Cindy Hoeks ; Michael Hiltensperger ; Bart Van Wijmeersch ; Veronica Popescu ; Lilian Aly ; Veerle Somers ; Thomas Korn ; Markus Kleinewietfeld ; Niels Hellings ; Bieke Broux

In autoimmunity, FOXP3+ regulatory T cells (Tregs) skew towards a pro-inflammatory, non-suppressive phenotype and are therefore unable to control the exaggerated autoimmune response. This largely impacts the success of autologous Treg therapy which is currently under investigation for autoimmune diseases, including multiple sclerosis (MS). There is a need to ensure in vivo Treg stability before successful application of Treg therapy. Using genetic fate-mapping mice, we demonstrate that inflammatory, cytokine-expressing exFOXP3 T cells accumulate in the central nervous system during experimental autoimmune encephalomyelitis. In a human in vitro model, we discovered that interaction with inflamed blood-brain barrier endothelial cells (BBB-ECs) induces loss-of-function by Tregs. Transcriptome and cytokine analysis revealed that in vitro migrated Tregs have disrupted regenerative potential, a pro-inflammatory Th1/17 signature and upregulate the mTORC1 signaling pathway. In vitro treatment of migrated human Tregs with the clinically-approved mTORC1 inhibitor rapamycin restored suppression. Finally, flow cytometric analysis indicated an enrichment of inflammatory, less suppressive CD49d+ Tregs in the cerebrospinal fluid of people with MS. In sum, interaction with BBB-ECs is sufficient to affect Treg function, and transmigration triggers an additive pro-inflammatory phenotype switch. These insights help improve the efficacy of autologous Treg therapy of MS.

2024-02-21·Brain & development

The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

Article

作者: Sthephanie Yannin Hernández-de la Cruz ; Thania Ordaz-Robles ; Marco Antonio Villaldama-Soriano ; Cristian Emmanuel Luna-Guzmán ; Tomas Almeida-Becerril ; Judith Villa-Morales ; Alan Cárdenas-Conejo ; Eugenia Dolores Ruíz-Cruz ; Jorge Maldonado-Hernandez ; Mariela Bernabe-Garcia ; Lourdes Barbosa-Cortés ; Maricela Rodríguez-Cruz

BACKGROUND:

In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown.

OBJECTIVE:

We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers.

METHODS:

This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation.

RESULTS:

Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation.

CONCLUSION:

FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

2024-02-10·Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[Association of ITGA4 and ICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease].

Article

作者: Dingli Zhang ; Hao Wu ; Xiaoxiao Shao ; Huiying Xiao ; Yi Jiang

OBJECTIVE:

To assess the association between the polymorphism of integral protein α4 (ITGA4) and intercellular adhesion molecule 1 (ICAM-1) genes and the risk and clinicopathological characteristics of Crohn's disease (CD) among Chinese patients.

METHODS:

From January 2010 to January 2021, a total of 215 CD patients and 529 gender- and age-matched healthy controls were enrolled from the Second Affiliated Hospital of Wenzhou Medical University as the study subjects. Genotypes of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) were determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Harvey-Bradshaw Index (HBI) was applied to assess the disease activity of CD, and the patients were further divided into subgroups based on the Montreal Classification Criteria of CD. Unconditional logistic regression was employed to analyze the distribution of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) polymorphisms between the patients and healthy controls and their association with the clinicopathological characteristics of the patients.

RESULTS:

The frequencies of T allele and CT+TT genotypes of ITGA4 (rs7562325) were higher in CD patients than the healthy controls (40.70% vs. 31.57%, P = 0.001; 62.79% vs. 54.36%, P = 0.042). The G variant and AG+GG genotypes of ITGA4 (rs6740847) were less common in patients with moderately to severely active CD compared with those with mildly active CD (31.18% vs. 51.72%, P = 0.002; 55.91% vs. 75.86%, P = 0.042). However, the opposite conclusion was drawn for the G allele (G) and AG+GG genotypes of ICAM-1 (rs5498) (31.45% vs. 17.24%, P = 0.027; 54.30% vs. 31.04%, P = 0.020). Compared with patients with terminal ileal or ileocolic CD, G allele and AG+GG genotypes of ITGA4 (rs6740847) were more prevalent in patients with colonic CD (55.26% vs. 29.38%, P < 0.001; 84.21% vs. 53.11%, P<0.001). The same conclusion could also be drawn for the G allele and AG+GG genotypes of ICAM-1 (rs5498) (42.11% vs. 26.84%, P = 0.008; 73.69% vs. 46.33%, P = 0.002). The frequency of homozygous GG genotype of ICAM-1 (rs5498) was lower in patients with stricturing and penetrating CD than those with non-stricturing and non-penetrating CD (0.00% vs. 12.32%, P = 0.001). The G allele and AG+GG genotypes of the ITGA4 (rs6740847) were more common in patients with perianal lesions than those without (40.28% vs. 30.77%, P = 0.049; 72.22% vs. 51.75%, P = 0.004).

CONCLUSION:

Variants of the ITGA4 (rs7562325) may be a risk factor for CD, whilst those of the ITGA4 (rs6740847) may be associated with the decline of disease activity and risk for colon involvement and perianal lesions. Variants of the ICAM-1 (rs5498) may increase the risk of disease activity and colonic involvement in CD patients, however, it may be a protective factor for stenosis and penetration. In addition, variants of the ITGA4 (rs6740847) and ICAM-1 (rs5498) may be associated with the early onset of CD.

项与 CD49d 相关的新闻（医药）

2024-03-19

·生物探索

JEV | 东南大学邱海波/巢杰发现败血症相关急性肺损伤的致病新机理

引言急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是一种常见的危及生命的综合征，目前尚无有效的药物治疗。败血症相关性ARDS是ARDS的主要类型，其致死率高于其他类型。细胞外囊泡(EVs)被认为是炎症性疾病发展中的新型介质。之前的研究表明，内皮细胞来源的EVs (EC-EVs)在ALI/ARDS的发展中起着至关重要的作用，但其机制仍不清楚。2024年3月15日，东南大学邱海波及巢杰共同通讯在Journal of Extracellular Vesicles在线发表题为“Endothelial cell-derived extracellular vesicles expressing surface VCAM1 promote sepsis-related acute lung injury by targeting and reprogramming monocytes”的研究论文，该研究发现循环EC-EVs的数量在败血症中增加，通过靶向单核细胞并将其重编程为促炎巨噬细胞，加剧了肺损伤。生物信息学分析和进一步的机制研究表明，败血症期间在EC-EVs上过表达的血管细胞粘附分子1 (VCAM1)通过与单核细胞表面而非组织巨噬细胞表面的整合素亚单位α 4 (ITGA4)相互作用激活NF-κB通路，从而调节单核细胞分化。这种作用可以通过降低EC-EVs中的VCAM1水平或阻断单核细胞上的ITGA4来减弱。此外，在败血症相关性ARDS患者中，VCAM1+ EC-EVs的数量显著增加。这些发现不仅揭示了先前未确定的败血症相关ALI/ARDS机制，而且为其精确治疗提供了潜在的新靶点和策略。急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是一种常见的呼吸危重综合征，由直接肺损伤(如肺炎、误吸)或非肺损伤(如败血症、创伤)引起，死亡率为35%至46% 。败血症相关性ARDS是ARDS的主要类型，其致死率高于其他类型。ARDS的本质是一种压倒性的、不受控制的炎症反应，其特征是炎症细胞大量浸润、细胞因子风暴形成、肺毛细血管通透性增加和肺水肿。尽管自1967年首次报道以来，在了解ARDS的发病机制方面取得了进展，但目前ARDS的治疗主要依赖于机械通气的支持性治疗，缺乏特异性和有效的药物治疗。这些治疗不能从根本上阻断疾病进展并改善患者的预后。因此，迫切需要探索新的靶点来抑制炎症级联反应的扩增。单核-巨噬细胞系统在ALI/ARDS的发生和发展中起着核心作用促炎型(M1型)和抗炎型(M2型)巨噬细胞失衡是ARDS发生的主要原因之一，其中M1巨噬细胞作为促炎表型，可促进ARDS的发生。巨噬细胞根据来源可分为组织常驻巨噬细胞(TR-Mφs)和单核细胞源性巨噬细胞(Mo-Mφs)。当感染发生时，经典Ly6Chigh单核细胞迁移到肺部并分化为Mo-Mφs以取代TR-Mφs。之前的大多数研究都将两者结合起来分析，认为它们在疾病中发挥着相同的功能。然而，最近越来越多的研究证明了两者之间意想不到的功能异质性。在SARS-CoV-2感染引起的ARDS中，Mo-Mφs驱动炎症反应，并且比TR-Mφs经历更显著的重编程，其中细胞表型因转录组变化而改变。在铜绿假单胞菌诱导的ALI小鼠模型中，Mo-Mφs与肺中其他细胞群(包括TR-Mφs)相比，M1巨噬细胞标志物(CD86、MHCII和iNOS)的表达更高。动物实验表明，外周血单核细胞的消耗可以降低ALI 。这些发现强烈提示Mo-Mφs在ARDS中起关键作用。在肺性ARDS中，单核细胞的募集和分化主要由肺泡细胞释放的趋化因子介导，这些趋化因子被病原体相关分子模式(pathogen-associated molecular patterns, PAMPs)或损伤相关分子模式(damage-associated molecular patterns, DAMPs)激活。然而，在非肺脓毒症相关的ARDS中，单核细胞在肺泡缺乏PAMPs和DAMPs的情况下从外周循环迁移到肺并分化为巨噬细胞的机制仍未得到充分研究。最近，新出现的证据表明，细胞外囊泡(EVs)参与调节免疫细胞功能和介导各种炎症性疾病的发展。EVs是脂质双层封闭囊泡，在正常和病理条件下几乎所有细胞类型都能释放，具有长距离细胞间通讯功能，稳定性好，作用持续时间长。有报道称，EVs介导肝脏疾病中单核细胞的募集和分化并在ARDS的发展中发挥作用。研究表明，与健康受试者相比，ARDS患者循环中内皮细胞源性细胞外囊泡(EC-EVs)的数量显著增加。早期对体外灌注人肺模型的研究发现，大肠杆菌诱导的体外人ALI模型的灌注液中的EVs主要来源于内皮细胞；将这些EVs注射到naïve人体肺部导致ALI，阻断EVs摄取后ALI降低。EC-EVs在败血症相关ALI/ARDS中的作用示意图（Credit: Journal of Extracellular Vesicles）该研究发现肺外败血症期间循环EC-EVs数量显著增加。值得注意的是，这些EC-EVs被单核细胞优先摄取，并在肺中被重编程为促炎巨噬细胞，导致细胞因子风暴和更多炎症细胞的浸润，从而加剧肺损伤。然而，这些EVs对肺TR-Mφs没有影响。生物信息学分析和进一步的机制研究表明，败血症期间在EC-EVs上过表达的VCAM1通过与单核细胞表面的ITGA4而不是TR-Mφs相互作用激活NF-κB通路，从而重新编程单核细胞(图10)。此外，在临床水平上，作者证实了VCAM1+ EC-EV在脓毒症相关ARDS患者中显著升高，这可能作为脓毒症患者ARDS发展的潜在生物标志物和靶点。这些发现不仅揭示了先前未确定的败血症相关ALI/ARDS机制，而且为其精确治疗提供了潜在的新靶点和策略。原文链接https://isevjournals.onlinelibrary.wiley.com/doi/full/10.1002/jev2.12423责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

临床结果

2023-12-18

·佰傲谷BioValley

跳出细胞疗法慢思路，iNKT疗法拓展自免赛道

NKT细胞是体内的自然杀伤T细胞，主要分为1型和2型，具有跨越先天和适应性免疫反应的多种功能。NKT细胞五分型及标志物循环型iNKT是CAR-NKT更优来源NKT细胞疗法靶向肿瘤是更常见的选择，通常选择1型iNKT作为目标细胞。iNKT通过iTCR识别由CD1d提呈的糖脂抗原、招募和反式激活NK细胞和T细胞以及极化免疫抑制TME的直接和间接作用杀伤肿瘤。不过想要通过NKT细胞的作用通路来治疗炎症自身免疫性疾病的药物还较少。2023年12月，GRI Bio宣布其候选产品GRI-0621治疗IPF的2a期临床试验即将开始患者入组。GRI-0621是一种1型恒定NKT（“iNKT”）拮抗剂。通过作为每日一次的口服胶囊，GRI-0621被设计为能够在炎症级联反应的早期抑制iNKT细胞的活性，从而防止细胞因子释放、细胞浸润，阻断疾病进展。NKT细胞已被证明可以在肺纤维化动物模型中驱动IPF病理学。与健康对照相比：IPF患者的BAL中，IFN-γ+、CD45+和整体NKT细胞的数量和比例显著增加；TGF-β1、SPP1和COL1A1显著增加；IPF中NKT细胞总数与气道巨噬细胞总数相关，但和肺功能FVC%无关。Front. Immunol.慢性炎症中NKT细胞作用NKT细胞可分为两类，1型也就是iNKT细胞促进炎症性疾病，而2型NKT细胞在几种慢性炎症性疾病中具有保护作用。组织驻留的iNKT优先定位在肺实质中，主要为三个亚群，分别对应影响1、2、3型免疫通路。NKT1表达T-bet，主要分泌GM-CSF和IFN-γ；NKT2表达GATA3和PLZFhigh，分泌IL-4、IL-5和IL-13；而NKT17则表达RORγt，分泌IL-17A和IL-22。iNKT亚群转录因子表征分泌的细胞因子NKT1 cellsPLZFlowT-bet+CD49a+CD122+CXCR3+CD4 (+/−)IFNγIL-4TNFNKT2 cellsPLZFhiICOS+CD4+IL-4IL-5IL-13NKT17 cellsPLZFintRORγt+ICOS+Syndecan 1+CD4−CCR6+CD103+NRP1+IL-17IL-22GM-CSFTNFNKTfh cellsBCL-6+CXCR5+PD1hiCD4+IL-21NKT10 cellsPLZF−E4BP4+CD49d+PD1+NRP1+IL-10IL-2在急性感染的情况下，iNKT起到保护组织、抑制炎症的作用，但是在过敏性哮喘等免疫相关炎症性疾病中，反而会加剧肺部炎症。在NASH、重型酒精性肝炎、狼疮性肾炎和IPF等一些涉及炎症性纤维化的疾病中：iNKT细胞被慢性激活，并分泌明显更高水平的促炎细胞因子；在损伤后iNKT细胞通过趋化因子受体CXCR6的相互作用而显著积聚；并且，IFN-γ+ iNKT细胞的增加与NAFLD活动评分的进展和患者的纤维化分期相关。iNKT细胞的激活会导致巨噬细胞显著增加、常规T细胞聚集被抑制、星形胶状细胞激活、以及小鼠纤维化组织中IL-1β、IL-6和TNF-α水平降低。Front. Immunol.随着纤维化的进展，慢性炎症组织中的三类iNKT细胞亚群很可能变为由其中一种或者两种亚群占据主导地位。在小鼠中的分布可见下图：Nat Rev Immunol.小结GBI Bio的这款iNKT细胞拮抗剂并未透露具体的拮抗机制，可能是类似TCR之类结合受体的方法。iNKT在肿瘤中的机制较为详细(肿瘤细胞治疗：NKT独特优势及临床进展)，慢性炎症和纤维化也是实体瘤的特征。如果能够准确把握亚群特征，不失为一种快速可行的开发思路。不过除了组织驻留iNKT，循环iNKT也可能会竞争这种拮抗作用，从而削弱对特定器官的治疗效果。参考文献：1.Kumar V, Hertz M, Agro A and Byrne AJ (2023) Type 1 invariant natural killer T cells in chronic inflammation and tissue fibrosis. Front. Immunol. 14:1260503. doi: 10.3389/fimmu.2023.12605032.Crosby CM, Kronenberg M. Tissue-specific functions of invariant natural killer T cells. Nat Rev Immunol. 2018 Sep;18(9):559-574. doi: 10.1038/s41577-018-0034-2. PMID: 29967365; PMCID: PMC6343475.3.https://www.biospace.com/article/releases/gri-bio-commences-patient-enrollment-in-phase-2a-biomarker-study-evaluating-lead-program-gri-0621-for-the-treatment-of-idiopathic-pulmonary-fibrosis-ipf-/4.https://gribio.com/gri-bio-presents-data-supporting-innovative-pipeline-of-nkt-cell-modulators-for-the-treatment-of-high-value-inflammatory-fibrotic-and-autoimmune-diseases/

细胞疗法免疫疗法临床结果临床2期临床1期

2023-07-24

·BioSpace

IPS HEART Announces Peer-Reviewed Publication in Cells of Aging Damage Reversal Showing GIVI-MPC Stem Cell Therapy’s Ability to Create New Skeletal Muscle in Aged Mice

GIVI-MPC targets site of muscle injury via direct injection and systemic delivery and creates new functional skeletal muscle for treatment of both Sarcopenia & Duchenne Muscular Dystrophy in aged mice HOUSTON--(BUSINESS WIRE)-- IPS HEART, a privately held cell therapy company advancing its stem cell platform to develop new skeletal muscle and cardiac muscle generation treatments for Duchenne Muscular Dystrophy (a rare disease) and heart failure, today announced the peer-reviewed publication of in vivo and in vitro study with its GIVI-MPC stem cell therapy candidate in this month's issue of Cells (volume 12, issue 14). The study, “Chemokine/ITGA4 Interaction Directs iPSC-Derived Myogenic Progenitor Migration to Injury Sites in Aging Muscle for Regeneration,” demonstrated GIVI-MPC stem cell therapy’s ability to successfully differentiate and create new human skeletal muscle in extremely aged 18-month aged mice for sarcopenia repair. Sarcopenia is characterized by muscle mass loss and function decline with age and poses a threat to the quality of lifelong health as well as the general well-being of the elderly population. Weaker muscles with low mass and function are likely more susceptible to muscle damage and injury. Studies suggest that muscle mass decreases by about 3 to 8 percent by decade after age 30. Thus far, there is no effective therapeutic approved for muscle loss during aging. “During aging, increased inflammation and oxidative damages in skeletal muscle tissues occur,” said Rauf Ashraf, Chief Executive Officer of IPS HEART. “Given that GIVI-MPCs possess anti-oxidative and anti-inflammatory properties, and exhibit superior migration characteristics, GIVI-MPCs administered in 18-month aged NSG mice resulted in significant improved muscle regeneration, with hindlimb grip strength doubling and an over 30% reduction in fibrosis. We are thrilled with these significant results and are even more pleased that GIVI-MPC has been featured in a second peer reviewed publication.” IPS HEART previously reported that GIVI-MPC developed into new human skeletal muscle, and reduced fibrosis & necrosis upon transplantation in dystrophic mice and pigs. In the current publication, successful delivery via IV/systemic delivery and direct injection were both achieved as well as new skeletal muscle generation with full length human dystrophin developed in 16-month aged dystrophic mice. This development further validates the idea that the Company’s therapeutic candidate may not only slow the rate of decline as gene therapy approaches aim for, but more importantly can potentially help reverse Duchenne Muscular Dystrophy in both young and older DMD patients. Heart disease continues to kill more people annually than all forms of cancer combined. IPS HEART’s first stem cell therapeutic (ISX9-CPC) helps longevity by creating new heart functional heart muscle and when paired with GIVI-MPC, new skeletal muscle can be created for sarcopenia thus providing tangible aging therapeutics for improved longevity. About IPS HEART IPS HEART is advancing its stem cell platform to develop new skeletal & cardiac muscle generation therapies.

细胞疗法基因疗法