Cell mediated gene therapy for muscular dystrophy: steps towards clinical efficacy.

这项研究旨在优化最近在杜氏肌营养不良症患者中测试的治疗方法，并将其扩展到另一种罕见的肌肉遗传疾病，以便将来可以将一种策略适用于更多疾病。肌肉营养不良是由单一基因突变引起的，导致人体肌肉功能受损和死亡。这反过来又会导致各种严重程度的残疾，在更严重的情况下，是毁灭性的，影响生活质量，导致过早死亡。虽然个别肌营养不良症是罕见或极其罕见的，但它们共同影响成千上万的人，并代表了国家卫生服务的重大挑战，负责提供姑息治疗和医疗援助，往往长达几十年。为了“治愈”遗传疾病，有必要替换或修复有缺陷的基因，这可以通过使用病毒载体（在实验室中经过修饰以将正确版本的基因传递到细胞中的病毒）或干细胞（可用于在体内产生任何其他类型细胞的细胞）来实现。为了确保它们被身体接受，干细胞可以来自相关的捐赠者（例如兄弟姐妹）或在实验室中“修复”后的患者本身。迄今为止，这些疗法已经成功地治疗了影响血液、皮肤和角膜的几种遗传疾病。这种方法之所以可行，是因为切除病变组织并替换它相对容易，但这种方法不适用于影响心脏、肝脏或大脑的疾病。在这种情况下，健康的细胞将不得不纠正遗传缺陷，并以某种方式帮助体内的病变细胞发挥功能。我们治疗的创新方面是基于这样一个事实，即注入患者动脉的干细胞最终均匀分布在全身。这些干细胞中的一些可以穿过血管，进入身体周围的组织并最终修复它。然而，这个过程还不够有效，不足以使患者得到明显的改善。为了实现这一目标，我们将通过一些使用人类干细胞的培养系统详细研究移植过程的每个步骤。该研究计划的成功完成将迅速导致新的临床试验，然后可能扩展到更罕见的肌肉遗传疾病，增加患者的受益。

This research aims to optimise a treatment that was recently tested in patients affected by Duchenne muscular dystrophy and extend it to another rare genetic diseases of the muscle, so that one strategy may in the future be adapted for more diseases. Muscular dystrophies are caused by mutations in a single gene that leads to the impairment of function and death of muscles in the human body. This in turn causes disability of variable severity that, in the worse cases, are devastating; compromising quality of life and leading to a premature death. Although individual muscular dystrophies are rare or extremely rare, together they affect many thousands of people and represent a major challenge for National Health Services, in charge of providing palliative therapies and medical assistance, often over decades. In order to "cure" genetic diseases it is necessary to replace or repair the defective gene and this can be achieved by using viral vectors (viruses that have been modified in the lab to deliver a correct version of the gene into cells) or stem cells (cells which can be used to generate any other type of cell in the body). To make sure they're accepted by the body, stem cells can be derived from a related donor (e.g. a sibling) or from the patient themselves, after having been "repaired" in the lab. These therapies have been successful so far for several genetic diseases affecting the blood, the skin, and the cornea. This has been possible because it is relatively easy to remove the diseased tissue and replace it. This approach is not possible for diseases affecting the heart, the liver or the brain. In these cases, healthy cells will have to correct the genetic defect and somehow help the function of the resident diseased cells.The innovative aspect of our treatment is based on the fact that stem cells which are injected into the arteries of patients end up distributed uniformly throughout the body. Some of these stem cells can then cross out of the blood vessel, move into the surrounding tissue of the body and eventually repair it. However, the process is not yet efficient enough to result in a noticeable improvement in patients. In order to achieve this, we will study in detail each step of the transplantation procedure through a number of culture system using human stem cells. The successful completion of the research programme will rapidly lead to new clinical trials and then may be extended to more rare genetic diseases of muscle, increasing the benefit to patients.