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Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
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巨型轴突神经病变的内基因疗法

Diana X Bharucha-Goebel1, Joshua J Todd1, Dimah Saade1

  • 1From the Neuromuscular and Neurogenetic Disorders of Childhood Section (D.X.B.-G., J.J.T., D.S., A.R.F., P.M., C.G.B), National Institute of Neurological Disorders and Stroke (G.N., T.L., J.D.H.), the Rehabilitation Medicine Department, Clinical Center (M.J., M.W.), National Eye Institute (W.M.Z., L.A.H.), and the National Institute of Allergy and Infectious Diseases, Division of Intramural Research (E.M.K.), National Institutes of Health, Bethesda, and the Departments of Neurology (C.J.S., A.H., T.O.C.), Neuroscience (C.J.S., A.H.), and Pediatrics (T.O.C.), Johns Hopkins University School of Medicine, Baltimore - all in Maryland; Children's National Hospital, Washington, DC (D.X.B.-G.); the University of Iowa, Iowa City (D.S.); the Department of Pediatrics and Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (R.M.B, S.J.G.), and Taysha Gene Therapies (E.T.) - both in Dallas; the Gene Therapy Program, University of Pennsylvania Perelman School of Medicine, Philadelphia (J.A.C.), Cencora PharmaLex, Conshohocken (B.P.C.), and Atorus Research, Newtown Square (B.S.) - all in Pennsylvania; Affinia Therapeutics, Waltham (R.C.), and the Rare Disease Research Unit, Pfizer, Cambridge (L.C., D.R.) - both in Massachusetts; the Departments of Pathology and Laboratory Medicine (D.A., T.W.B.) and Radiology (D.A.), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; and the Department of Pathology, Stanford University School of Medicine, Stanford, CA (J.E.H.).

The New England journal of medicine
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概括

这项研究探讨了巨型轴突神经病变的基因疗法,发现内scAAV9/JeT-GAN在某些剂量下显示出潜在的运动功能益处. 需要进一步的研究来确认治疗这种罕见的神经退行性疾病的安全性和有效性.

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科学领域:

  • 神经科学是一个神经科学.
  • 遗传学 是一个遗传学.
  • 儿科 儿科 儿科

背景情况:

  • 巨型轴突神经病变 (GAN) 是一种罕见的,遗传性神经退行性疾病,影响儿童.
  • 它是由GAN基因的突变引起的,导致gigaxonin缺乏.
  • 这种情况呈现出多种影响神经系统的症状.

研究的目的:

  • 评估使用scAAV9 / JeT-GAN在患有GAN的儿童中进行内基因治疗的安全性和有效性.
  • 根据运动功能的测量来确定减缓疾病进展的最佳剂量.

主要方法:

  • 一项剂量升级研究,涉及14名患有GAN的儿科参与者.
  • 管理四种不同的内剂量scAAV9/JeT-GAN.
  • 主要终点:安全;次要终点:使用运动功能测量 (MFM) 在1年内减缓运动功能下降.

主要成果:

  • 最高剂量 (1.8×10^14vg) 实现了99%的减缓MFM得分下降的概率,超过了疗效值.
  • 一些参与者表现出改善或稳定的感觉神经动作潜能幅度.
  • 观察到不良事件,其中一个严重事件可能与治疗有关.

结论:

  • 内 scAAV9/JeT-GAN 基因疗法在患有 GAN 的儿童中显示出对运动功能和神经传导的潜在益处.
  • 虽然一般耐受性很好,但不良事件需要仔细监测.
  • 需要进一步调查,以确定这种基因治疗方法对GAN的长期安全性和有效性.