Efficacy of oligodendrocyte precursor cells as delivery vehicles for single-chain variable fragment to misfolded SOD1 in ALS rat model

Sumio Minamiyama, Madoka Sakai, Yuko Yamaguchi, Makiko Kusui, Hideki Wada, Ryota Hikiami, Yoshitaka Tamaki, Megumi Asada-Utsugi, Akemi Shodai, Akiko Makino, Noriko Fujiwara, Takashi Ayaki, Takakuni Maki, Hitoshi Warita, Masashi Aoki, Keizo Tomonaga, Ryosuke Takahashi, Makoto Urushitani

Research output: Contribution to journalArticlepeer-review


Superoxide dismutase1 (SOD 1) mutation is a leading cause of familial amyotrophic lateral sclerosis (ALS). Growing evidence suggests that antibody therapy against misfolded SOD1 protein can be therapeutic. However, the therapeutic effects are limited, partly because of the delivery system. Therefore, we investigated the efficacy of oligodendrocyte precursor cells (OPCs) as a drug delivery vehicle of single-chain variable fragments (scFv). Using a Borna disease virus vector that is pharmacologically removable and episomally replicable in the recipient cells, we successfully transformed wild-type OPCs to secrete scFv of a novel monoclonal antibody (D3-1), specific for misfolded SOD1. Single intrathecal injection of OPCs scFvD3-1, but not OPCs alone, significantly delayed disease onset and prolonged the lifespan of ALS rat models expressing SOD1 H46R. The effect of OPC scFvD3-1 surpassed that of a 1 month intrathecal infusion of full-length D3-1 antibody alone. scFv-secreting OPCs suppressed neuronal loss and gliosis, reduced levels of misfolded SOD1 in the spinal cord, and suppressed the transcription of inflammatory genes, including Olr1, an oxidized low-density lipoprotein receptor 1. The use of OPCs as a delivery vehicle for therapeutic antibodies is a new option for ALS in which misfolded protein and oligodendrocyte dysfunction are implicated in the pathogenesis.

Original languageEnglish
Pages (from-to)312-329
Number of pages18
JournalMolecular Therapy - Methods and Clinical Development
Publication statusPublished - 2023 Mar 9


  • amyotrophic lateral sclerosis (ALS)
  • oligodendrocyte precursor cells
  • single-chain variable fragments (scFv)
  • superoxide dismutase 1 (SOD1)
  • transplantation
  • viral vector

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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