Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden
Biochem Soc Trans. 2017 Dec 15;45(6):1279-1293. doi: 10.1042/BST20170141. Epub 2017 Nov 10.
Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million individuals. HGPS is usually caused by a point mutation in exon 11 of the gene (c.1824C>T, p.G608G), resulting in the increased usage of a cryptic splice site and production of a truncated unprocessed lamin A protein named progerin. Since the genetic cause for HGPS was published in 2003, numerous potential treatment options have rapidly emerged. Strategies to interfere with the post-translational processing of lamin A, to enhance progerin clearance, or directly target the HGPS mutation to reduce the progerin-producing alternative splicing of the gene have been developed. Here, we give an up-to-date resume of the contributions made by our and other research groups to the growing list of different candidate treatment strategies that have been tested, both , in mouse models for HGPS and in clinical trials in HGPS patients.
亨廷顿氏舞蹈症-吉福德早衰综合征（HGPS，早衰症）是一种罕见的儿童早发性进行性衰老疾病，发病率约为每 1800 万人中有 1 例。HGPS 通常由 基因第 11 外显子中的点突变（c.1824C>T，p.G608G）引起，导致隐匿剪接位点的增加使用和产生名为 progerin 的截断未加工的核纤层 A 蛋白。自 2003 年发表 HGPS 的遗传病因以来，迅速出现了许多潜在的治疗选择。已经开发了各种策略来干扰核纤层 A 的翻译后加工、增强 progerin 清除或直接针对 HGPS 突变以减少 基因产生 progerin 的选择性剪接。在这里，我们总结了我们和其他研究小组对不断增加的不同候选治疗策略的贡献，这些策略已在 HGPS 的小鼠模型和 HGPS 患者的临床试验中进行了测试。
