Preclinical gene therapy for genetic urinary bladder disease

遗传性膀胱疾病的临床前基因治疗

• 批准号: MR/T016809/1
• 负责人: Adrian Woolf
• 金额: $ 62.12万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT016809%2F1
• 关键词: Preclinical; gene; therapy; genetic; urinary

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.

在这个项目中，我们将测试治疗一种毁灭性的膀胱疾病。这种疾病在家庭中流行，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，这种疾病还没有治愈的方法，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已经在患有这种疾病的人中发现了两种缺陷基因。我们发现这些基因控制神经如何生长到膀胱中。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让我们通过水。我们还研究了具有相同遗传条件的小鼠。像患有这种疾病的人一样，老鼠也有排空膀胱的困难。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小鼠。该疗法是在小鼠出生后立即给予的，以便在疾病造成太大损害之前给予最佳治疗机会。我们项目的成功结果将是治愈儿童期严重膀胱疾病患者的第一步。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能用于其他危及生命的影响肾脏和膀胱的遗传性疾病。这些疾病是儿童和年轻人肾衰竭的重要原因，但目前还没有确定的治疗方法。

项目成果

Narrowing the chromosome 22q11.2 locus duplicated in bladder exstrophy-epispadias complex.

缩小膀胱外翻-尿道上裂复合体中复制的染色体 22q11.2 位点。

• DOI: 10.1016/j.jpurol.2022.04.006
• 发表时间: 2022
• 期刊: Journal of pediatric urology
• 影响因子: 2
• 作者: Beaman GM

Definition, diagnosis and clinical management of non-obstructive kidney dysplasia: a consensus statement by the ERKNet Working Group on Kidney Malformations.

• DOI: 10.1093/ndt/gfac207
• 发表时间: 2022-11-23
• 期刊: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Predicting congenital renal tract malformation genes using machine learning.

• DOI: 10.1038/s41598-023-38110-z
• 发表时间: 2023-08-14
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Kabir, Mitra;Stuart, Helen M.;Lopes, Filipa M.;Fotiou, Elisavet;Keavney, Bernard;Doig, Andrew J.;Woolf, Adrian S.;Hentges, Kathryn E.
• 通讯作者: Hentges, Kathryn E.

Neurogenic Defects Occur in LRIG2-Associated Urinary Bladder Disease.

LRIG2相关膀胱疾病中发生神经源缺陷。

• DOI: 10.1016/j.ekir.2023.04.017
• 发表时间: 2023-07
• 期刊: KIDNEY INTERNATIONAL REPORTS
• 影响因子: 6
• 作者: Grenier, Celine;Lopes, Filipa M.;Cueto-Gonzalez, Anna M.;Rovira-Moreno, Eulalia;Gander, Romy;Jarvis, Benjamin W.;McCloskey, Karen D.;Gurney, Alison M.;Beaman, Glenda M.;Newman, William G.;Woolf, Adrian S.;Roberts, Neil A.
• 通讯作者: Roberts, Neil A.

Early B-cell Factor 3-Related Genetic Disease Can Mimic Urofacial Syndrome.

• DOI: 10.1016/j.ekir.2020.07.001
• 发表时间: 2020-10
• 期刊: Kidney international reports
• 影响因子: 6
• 作者: Harkness JR;Beaman GM;Teik KW;Sidhu S;Sayer JA;Cordell HJ;Thomas HB;Wood K;Stuart HM;Woolf AS;Newman WG
• 通讯作者: Newman WG