中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (3): 558-559.doi: 10.4103/1673-5374.350202

• 观点:视神经损伤修复保护与再生 • 上一篇    下一篇

治疗神经元蜡样脂褐质沉积症的神经退行性变的策略：对视网膜的看法

  

  • 出版日期:2023-03-15 发布日期:2022-08-26

Strategies to treat neurodegeneration in neuronal ceroid lipofuscinosis: a view onto the retina

Udo Bartsch*   

  1. Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Online:2023-03-15 Published:2022-08-26
  • Contact: Udo Bartsch, PhD, ubartsch@uke.de.
  • Supported by:
    This work was supported by the “Stiftung zur Förderung der Universitätsmedizin Hamburg” and the “Ernst and Berta Grimmke Stiftung” (to UB).

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摘要： https://orcid.org/0000-0003-3227-7568 (Udo Bartsch)

Abstract: Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease, is the umbrella term for a group of neurodegenerative lysosomal storage disorders with onset mainly in childhood. The total 13 genetically distinct NCLs are caused by mutations in genes encoding soluble or transmembrane proteins, and have been classified according to the affected gene into CLN1 to CLN8 and CLN10 to CLN14. Intracellular accumulation of autofluorescent storage material due to lysosomal dysfunction is a hallmark of all NCLs. Patients affected by this fatal life-limiting disorder typically present with mental retardation, motor impairment, epileptic seizures, and brain atrophy. Progressive retinal degeneration and vision loss are other hallmarks of the majority of NCLs (for details, see Kohlschutter et al., 2019). Rare cases of patients presenting with non-syndromic retinal dystrophies indicate that the retina is particularly sensitive to lysosomal dysfunctions in some NCLs. With the only exception of a brain-directed enzyme replacement therapy (ERT) for CLN2 disease, a condition caused by dysfunctions of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1), there are currently no approved treatment options for these fatal disorders. Studies on animal models of different NCLs have demonstrated the efficacy of various treatment strategies to attenuate neurodegeneration in the brain, and some of them are currently being evaluated in clinical trials (Kohlschutter et al., 2019). The preclinical data and first results from an ERT and a gene therapy trial on CLN2 patients suggest, however, that brain-directed treatments have no or only a minor therapeutic impact on retinal degeneration and vision loss (discussed in Liu et al., 2022). Thus, there is a need to combine retina- and brain-directed therapies to combat both vision loss and neurological symptoms. In fact, preservation of vision not only requires preservation of retina function but additionally functional preservation of the visual centers in the brain.