Genespire在 ASGCT 2025上展示了关于 MMA肝脏定向基因治疗的乐观临床前数据相关的帖子：-动脉网

Genespire Presents Promising Preclinical Data on Liver-Directed Gene Therapy for MMA at ASGCT 2025 Related posts:

GeneOnline 等信源发布 2025-05-14 15:58



可切换为仅中文







by Denisse Sandoval

由丹妮丝·桑多瓦尔

Share To

分享到

enespire

激励

presented

呈现

positive preclinical data on dosing for its first-in-human, in vivo liver-directed gene therapy for methylmalonic acidemia (MMA) during an oral presentation at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in Baltimore, Maryland. The therapy offers an off-the-shelf gene therapy solution for pediatric patients with genetic diseases.

在马里兰州巴尔的摩举行的第28届美国基因与细胞治疗学会（ASGCT）年会上，通过口头报告展示了其针对甲基丙二酸血症（MMA）的首次人体内、肝脏导向基因治疗的临床前剂量积极数据。该疗法为患有遗传病的儿童患者提供了一种现成的基因治疗方案。

The presentation took place as part of the ongoing ASGCT Annual Meeting 2025..

该报告是在2025年ASGCT年会持续进行期间发布的。

Preclinical Study on Immune-Shielded Lentiviral Vectors Shows Promising Results and Potential for Human Clinical Trials

临床前免疫屏蔽慢病毒载体研究显示可喜结果，具备人体临床试验潜力

At the 28th Annual Meeting of the ASGCT, researchers presented findings on an immune-shielded lentiviral vector (ISLV) encoding a human MUT transgene, administered intravenously in a mouse model of methylmalonic acidemia (MMA). The therapy successfully delivered a functional MMUT gene to liver cells, resulting in effective treatment outcomes.

在ASGCT第28届年会上，研究人员展示了一种免疫屏蔽慢病毒载体（ISLV）的发现，该载体编码人类MUT转基因，并在甲基丙二酸血症（MMA）的小鼠模型中通过静脉注射给药。该疗法成功将功能性MMUT基因递送到肝细胞，取得了有效的治疗效果。

A codon-optimized version, ISLV.MMUTco, demonstrated greater efficacy at lower doses compared to the wild-type vector. Researchers observed dose-dependent improvements across three dosing levels, with even the lowest dose producing therapeutic benefits due to the selective advantage of genetically corrected cells..

一个密码子优化版本ISLV.MMUTco在较低剂量下显示出比野生型载体更高的效力。研究人员在三个剂量水平上观察到与剂量相关的改善，即使最低剂量也因基因校正细胞的选择性优势而产生了治疗效果。

The study also used humanized mouse models to evaluate dosing strategies relevant for clinical translation. Results indicated that CD47-enriched vectors maintained therapeutic efficacy at significantly reduced doses, offering a potential path to safer and more efficient treatment in humans. These preclinical findings provide a strong foundation for advancing ISLV-based gene therapy into clinical trials for MMA..

该研究还使用了人源化小鼠模型来评估与临床转化相关的剂量策略。结果表明，富含CD47的载体在显著降低的剂量下仍保持治疗效果，为人类更安全和更有效的治疗提供了潜在途径。这些临床前研究结果为推进基于ISLV的基因疗法进入MMA临床试验奠定了坚实基础。

Dr. Elena Barbon, Research Scientist, and Professor Alessio Cantore, Group Leader, conducted the study at the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) in collaboration with Genespire. Professor Alessio Cantore, Group Leader at SR-TIGET and co-founder of Genespire, provided commentary on the findings by stating, “We are very proud to have secured another oral presentation slot at the highly respected ASGCT conference.

埃琳娜·巴尔邦博士，研究员，以及亚历西奥·坎托雷教授，团队负责人，在圣拉斐尔Telethon基因治疗研究所（SR-TIGET）与Genespire合作开展了这项研究。SR-TIGET的团队负责人、Genespire的联合创始人亚历西奥·坎托雷教授在评论研究结果时表示：“我们非常自豪能够在备受尊敬的ASGCT会议上再次获得口头报告的机会。

These interesting data provide us with further preclinical validation on our integrative immune shielded lentiviral vector (LV)-based gene therapy as we progress toward the clinic.”.

这些有趣的数据为我们基于整合性免疫屏蔽慢病毒载体（LV）的基因疗法提供了进一步的临床前验证，因为我们正在向临床迈进。

MMA Incidence Rates Show Variability Across Regions with 1 in 50,000 in Japan & 1 in 85,000 in Taiwan

MMA发病率在不同地区显示出差异，日本为1/50,000，台湾为1/85,000。

Methylmalonic acidemia (MMA)

甲基丙二酸血症 (MMA)

is a

是

rare genetic metabolic disorder primarily caused by mutations in the gene encoding the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). The condition impairs the body’s ability to process certain proteins

罕见的遗传性代谢紊乱，主要由编码线粒体酶甲基丙二酰辅酶A变位酶（MUT）的基因突变引起。该状况会损害身体处理某些蛋白质的能力。

and

和

fats, leading to the accumulation of methylmalonic acid, which can damage the brain, liver, kidneys, and other organs.

脂肪，导致甲基丙二酸的积累，这种酸会损害大脑、肝脏、肾脏和其他器官。

Estimates of methylmalonic acidemia (MMA)

甲基丙二酸血症（MMA）的估计

incidence

发生率

vary by region, with reported rates of 1 in 50,000 in Japan, 1 in 250,000 in Germany, and 1 in 85,000 in Taiwan.

因地区而异，在日本报告的发病率为1/50,000，德国为1/250,000，台湾为1/85,000。

Currently, no disease-targeted therapies are approved for MMA

目前，尚无针对MMA的疾病靶向疗法获批。

. Management primarily relies on dietary restrictions, including low-protein diets to limit the intake of certain amino acids, and supportive treatments such as carnitine supplementation or intermittent dialysis to reduce toxic metabolite buildup. However, these approaches only mitigate symptoms and do not address the underlying genetic defect..

管理主要依赖于饮食限制，包括低蛋白饮食以限制某些氨基酸的摄入，以及支持性治疗，如肉碱补充或间歇性透析以减少有毒代谢物的积累。然而，这些方法只能缓解症状，并不能解决潜在的基因缺陷。

Clinicians may consider liver or combined liver-kidney transplantation in severe cases to stabilize metabolic function, but these procedures carry substantial risks and do not offer a cure. Researchers are actively exploring gene therapy as a promising approach to restore functional MMUT enzyme activity and provide a long-term solution.

临床医生可能会在严重情况下考虑肝移植或肝肾联合移植以稳定代谢功能，但这些手术存在较大风险，且无法治愈。研究人员正在积极探索基因疗法作为一种有前景的方法，用以恢复功能性MMUT酶活性并提供长期解决方案。

Several preclinical studies, including those involving lentiviral and AAV vectors, have shown potential in correcting the metabolic defect in animal models..

几项临床前研究，包括涉及慢病毒和AAV载体的研究，已显示出在动物模型中纠正代谢缺陷的潜力。

Karen Aiach-Pignet, Genespire’s CEO

凯伦·艾亚赫-皮格内，Genespire公司首席执行官

added

添加

, “These data will help determine the dosing level for our anticipated Phase I clinical trial of GENE202 next year”, She added, “It is an exciting time to work at Genespire. There is a real sense of momentum in developing in vivo gene therapies following the acquisition of EsoBiotec by AstraZeneca earlier this year which has attracted a lot of interest in our work.”.

“这些数据将有助于确定我们预计明年进行的GENE202一期临床试验的剂量水平，”她补充说，“在Genespire工作是一个令人兴奋的时刻。今年早些时候阿斯利康收购EsoBiotec后，我们在开发体内基因疗法方面感受到了真正的动力，这也吸引了很多人对我们工作的兴趣。”