Preclinical gene therapy for genetic urinary bladder disease

在这个项目中，我们将测试一种毁灭性膀胱疾病的治疗方法。这种疾病在家庭中遗传，使儿童和成人无法完全排空膀胱。相反，尿液在膀胱中积聚并受到感染，导致肾衰竭。目前还没有治愈这种疾病的方法，受影响的人需要每天多次将导尿管插入膀胱以排出尿液。我们的曼彻斯特研究小组在患有这种疾病的人身上发现了两个有缺陷的基因。我们发现这些基因控制着神经如何在膀胱中生长。这些神经控制我们的膀胱如何填满和储存尿液，也控制我们的膀胱如何改变形状以让我们排水。我们还研究了具有相同遗传条件的老鼠。和患有这种疾病的人一样，老鼠排空膀胱也有困难。在这个项目中，我们将使用“基因疗法”来治愈这些患有遗传性膀胱疾病的老鼠。这种疗法是在老鼠刚出生时进行的，以便在疾病造成太大损害之前有最好的机会治疗这种疾病。我们项目的成功结果将是治愈儿童时期患有严重膀胱疾病的人的第一步。这将意味着这些人不再有终身尿失禁。未来，这种新型治疗方法可用于其他危及生命的遗传性疾病，这些疾病会影响肾脏和膀胱。这些疾病是儿童和年轻人肾衰竭的重要原因，但目前还没有明确的治疗方法。

In this project we will test cures for a devastating bladder disease. This disease runs in families and makes children and adults unable to fully empty their bladders. Instead, urine builds up in the bladder and becomes infected, causing kidney failure. At present there is no cure for this disease and affected people need to put a catheter into their bladder several times a day to drain urine.Our Manchester research team have identified two faulty genes in people who have this disease. We discovered that these genes control how nerves grow into the bladder. These same nerves then control how our bladders fill up and store urine, and also control how our bladders change shape to let us pass water. We also study mice with the same genetic condition. Like people with the disease, the mice have trouble emptying their bladders. In this project we will use 'gene therapy' to cure these mice that have genetic urinary bladder disease. The therapy is given to mice just after they are born to give the best chance of treating the disease before it has done too much damage.The successful outcome of our project will be a first step towards curing people with severe bladder disease beginning in childhood. This would mean that these people no longer have life-long incontinence of urine.In future, this new type of treatment could be used in other life-threatening inherited genetic diseases that affect the kidney and urinary bladder. Such diseases are important causes of kidney failure in children and young adults and yet they currently have no definitive cures.