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Nature Medcine:早衰症治疗新法

来源:新华网 2008-06-30 15:40

生物谷报道:据《自然—医学》杂志,西班牙和法国的一些研究人员成功地在老鼠身上完成了早衰症治疗实验。这种迄今为止无法医治的疾病导致全球100多名孩子提前衰老。

借助电视募捐资金资助早衰症治疗研究工作的法国抗肌病防治协会指出,不久之后,欧洲25个患有此病的儿童当中的15人将接受实验治疗。如果治疗申请获得批准,患者将会在马赛一座医院接受来自法国全国保健和医学研究所的尼古拉·莱维领导的临床实验。

早衰是一种非常罕见的疾病(法国已知有3例),患病儿童自出生便感染。这些儿童的外貌和某些生理畸形如同上了年纪的人:头发稀少,皮肤很薄且无毛,关节僵硬,有心血管问题。早衰症在此之前没有任何治疗方法,患病儿童的平均寿命都很短,平均12岁至13岁。

尼古拉·莱维与来自西班牙奥维耶多大学医学院的卡洛斯·洛佩斯-奥廷领导的研究队伍在老鼠身上进行了试验,方法是将现有的两种分子statine(被用来降低血液中胆固醇含量,预防心血管风险)与aminobisphosphonate(用于治疗骨质疏松症)化合。

早衰症的发生是由于早衰蛋白质(progerin)在细胞中蓄积。研究人员对老鼠和试管内的患者细胞进行的实验显示,上述两种分子的化合能够制止早衰蛋白质的毒性。病情的发展因而会减轻、放慢。这样,这种治疗方法就能够减少疾病的效果(生长推迟,体重下降,毛发脱落,骨质脆弱),提高老鼠的平均寿命:从平均101天增至179天。

针对患病儿童的临床实验将持续3年。不过,尼古拉·莱维在5月份曾指出,如果没有出现严重的不受欢迎的结果,治疗将可“终身”进行。

研究人员认为,除了治疗早衰症外,这些研究成果还将有助于更好地了解正常衰老机制。(生物谷bioon.com)

生物谷推荐原始出处:

Nature Medcine,Ignacio Varela, Nicolas Lévy, Carlos López-Otín

Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging

Ignacio Varela1, Sandrine Pereira2, Alejandro P Ugalde1, Claire L Navarro2, María F Suárez1, Pierre Cau2, Juan Cadiñanos1, Fernando G Osorio1, Nicolas Foray3, Juan Cobo4, Félix de Carlos4, Nicolas Lévy2, José M P Freije1 & Carlos López-Otín1

Several human progerias, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by the accumulation at the nuclear envelope of farnesylated forms of truncated prelamin A, a protein that is also altered during normal aging1, 2. Previous studies in cells from individuals with HGPS have shown that farnesyltransferase inhibitors (FTIs) improve nuclear abnormalities associated with prelamin A accumulation, suggesting that these compounds could represent a therapeutic approach for this devastating progeroid syndrome3. We show herein that both prelamin A and its truncated form progerin/LA50 undergo alternative prenylation by geranylgeranyltransferase in the setting of farnesyltransferase inhibition, which could explain the low efficiency of FTIs in ameliorating the phenotypes of progeroid mouse models. We also show that a combination of statins and aminobisphosphonates efficiently inhibits both farnesylation and geranylgeranylation of progerin and prelamin A and markedly improves the aging-like phenotypes of mice deficient in the metalloproteinase Zmpste24, including growth retardation, loss of weight, lipodystrophy, hair loss and bone defects. Likewise, the longevity of these mice is substantially extended. These findings open a new therapeutic approach for human progeroid syndromes associated with nuclear-envelope abnormalities.

  1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, calle Fernando. Bongera s/n, 33006-Oviedo, Spain.
  2. Institut National de la Sante et de la Recherche Medicale UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Université de la Méditerranée, Faculté de Médecine, 13385 Marseille Cedex 05, France.
  3. Institut National de la Sante et de la Recherche Medicale U647, ID17, European Synchrotron Research Facility, 6 rue Jules Horowitz, 38043-Grenoble, France.
  4. Departamento de Cirugía y Especialidades Médico-Quirúrgicas, and Instituto Asturiano de Odontología, calle Julián Clavería 6, Universidad de Oviedo, 33006-Oviedo, Spain.
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