Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.
Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.
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DOI：
10.1016/j.ymthe.2022.09.017
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发表时间：
2023-01-04
影响因子：
12.4
通讯作者：
Bongarzone, Ernesto R.
中科院分区：
文献类型：
--
作者：
Heller, Gregory;Bradbury, Allison M.;Sands, Mark S.;Bongarzone, Ernesto R.
克拉伯病（KD）是一种由 galc 基因突变引起的溶酶体贮积病（LSD）。单基因LSD有50多种，在很大程度上阻碍儿童的正常发育，并常常导致过早死亡。目前，LSD 尚无治愈方法，可用的治疗方法通常不足、作用短，而且并非没有并发症或长期副作用。过去 30 年，我们对 LSD 病理学和治疗方案的理解取得了重大进展。基于这些进展，最近启动了两项基于基因治疗的 KD 临床试验 NCT04693598 和 NCT04771416。这篇综述将讨论我们对生酮饮食的了解是如何达到今天的水平的，重点是临床前研究，以及我们的发现如何证明对其他 LSD 的治疗有益。目前克拉伯病的标准护理治疗（造血干细胞移植）只能适度延长预期寿命并部分预防症状。基于腺相关病毒的基因治疗是克拉伯病最有效的单一疗法。总体而言，联合疗法是延长预期寿命和预防疾病症状最有效的治疗方法。
Krabbe disease (KD) is a lysosomal storage disease (LSD) caused by mutations in the galc gene. There are over 50 monogenetic LSDs, which largely impede the normal development of children and often lead to premature death. At present, there are no cures for LSDs and the available treatments are generally insufficient, short acting, and not without co-morbidities or long-term side effects. The last 30 years have seen significant advances in our understanding of LSD pathology as well as treatment options. Two gene therapy-based clinical trials, NCT04693598 and NCT04771416, for KD were recently started based on those advances. This review will discuss how our knowledge of KD got to where it is today, focusing on preclinical investigations, and how what was discovered may prove beneficial for the treatment of other LSDs. The current standard-of-care treatment of Krabbe disease (hematopoietic stem cell transplantation) only moderately increases life expectancy and partially protects against symptoms. Adeno-associated virus-based gene therapy is the most effective single-modality treatment of Krabbe disease. Combination therapies are the overall most effective treatments to increase life expectancy and protect against disease signs.
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影响因子：
12.4
作者：
Cearley, CN;Wolfe, JH
通讯作者：
Wolfe, JH
DOI：
10.1038/mt.2008.166
发表时间：
2008-10
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.9
作者：
Bradbury, Allison M.;Bagel, Jessica H.;Vite, Charles H.
通讯作者：
Vite, Charles H.
影响因子：
16.6
作者：
Adewoye, Adeolu B.;Lindsay, Sarah J.;Dubrova, Yuri E.;Hurles, Matthew E.
通讯作者：
Hurles, Matthew E.
影响因子：
5.4
作者：
Afione, SA;Conrad, CK;Flotte, TR
通讯作者：
Flotte, TR