Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease)

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Review

Hawkins-Salsbury, Jacqueline A.¹  Cooper, Jonathan D.^3,4  Sands, Mark S.^1,2 

[1] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[3] Kings Coll London, Kings Hlth Partners Ctr Neurodegenerat Res, Ctr Cellular Basis Behav, Inst Psychiat,Dept Neurosci,James Black Ctr, London SE5 9NU, England

[4] Kings Coll London, Kings Hlth Partners Ctr Neurodegenerat Res, Ctr Cellular Basis Behav, Pediat Storage Dis Lab,James Black Ctr, London SE5 9NU, England

关键词: Neuronal ceroid lipofuscinosis;    Batten disease;    Neurodegeneration;    Neuroinflammation;    Lysosomal storage disease;    Gene therapy;   

DOI  :  10.1016/j.bbadis.2013.05.026

来源: Elsevier

【 摘 要 】

The neuronal ceroid lipofuscinoses (NCL, Batten disease) are a group of inherited neurodegenerative diseases. Infantile neuronal ceroid lipofuscinosis (INCL, infantile Batten disease, or infantile CLN1 disease) is caused by a deficiency in the soluble lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1) and has the earliest onset and fastest progression of all the NCLs. Several therapeutic strategies including enzyme replacement, gene therapy, stem cell-mediated therapy, and small molecule drugs have resulted in minimal to modest improvements in the murine model of PPT1-deficiency. However, more recent studies using various combinations of these approaches have shown more promising results; in some instances more than doubling the lifespan of PPT1-deficient mice. These combination therapies that target different pathogenic mechanisms may offer the hope of treating this profoundly neurodegenerative disorder. Similar approaches may be useful when treating other forms of NCL caused by deficiencies in soluble lysosomal proteins. Different therapeutic targets will need to be identified and novel strategies developed in order to effectively treat forms of NCL caused by deficiencies in integral membrane proteins such as juvenile neuronal ceroid lipofuscinosis. Finally, the challenge with all of the NCLs will lie in early diagnosis, improving the efficacy of the treatments, and effectively translating them into the clinic. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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