中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (2): 355-359.doi: 10.4103/1673-5374.377606

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

IIIB型粘多糖病:AAV疗法的现状回顾和探索

  

  • 出版日期:2024-02-15 发布日期:2023-08-30

Mucopolysaccharidosis type IIIB: a current review and exploration of the AAV therapy landscape

Courtney J. Rouse1, Victoria N. Jensen1, Coy D. Heldermon2, *   

  1. 1Lacerta Therapeutics, Alachua, FL, USA; 2University of Florida College of Medicine, Gainesville, FL, USA
  • Online:2024-02-15 Published:2023-08-30
  • Contact: Coy D. Heldermon, MD, PhD, coy.heldermon@medicine.ufl.edu.
  • Supported by:
    This work was supported by Sanfilippo Children’s Foundation, Sanfilippo Fundacja and Sanfilippo Initiative, Cure Sanfilippo, Lacerta Therapeutics, and NIH/NINDS R01NS102624 (to CDH).

摘要: https://orcid.org/0000-0002-2148-2868 (Coy D. Heldermon)

Abstract: Mucopolysaccharidoses type IIIB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase. This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction. Current treatment options are expensive, limited, and presently there are no approved cures for mucopolysaccharidoses type IIIB. Adeno-associated virus gene therapy has significantly advanced the field forward, allowing researchers to successfully design, enhance, and improve potential cures. Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels, auditory function, and lifespan in the murine model for mucopolysaccharidoses type IIIB to that seen in healthy mice. Here, we review the current state of the field in relation to the capsid landscape, adeno-associated virus gene therapy and its successes and challenges in the clinic, and how novel adeno-associated virus capsid designs have evolved research in the mucopolysaccharidoses type IIIB field.

Key words: adeno-associated virus, central nervous system, gene therapy, heparan sulfate, immune response, mucopolysaccharidoses type IIIB, N-acetyl-alpha-glucosaminidase, newborn screening