医療者の立場から考える希少神経難病に対する臨床試験の課題と解決策

抄録

Ongoing advances in gene therapy and novel pharmaceutical platforms have accelerated the development of treatments for various rare neurological disorders. However, due to small patient populations, heterogeneity in disease progression, and high development costs, conducting large–scale randomized controlled trials (RCTs) is often infeasible. As a result, many rare neurological diseases remain without effective therapies.

This article reviews the current landscape of clinical trials in rare neurological diseases and explores the concept of individualized clinical trials. We focus particularly on antisense oligonucleotide–based therapies (ASOs) and discuss notable examples of N–of–1 drug development, such as the n–Lorem Foundation and Silence ALS program in the United States. We also highlight ongoing efforts in Japan, including initiatives supported by the Japan Agency for Medical Research and Development (AMED).

Individualized clinical trials, including N–of–1 designs, show promise in addressing the unmet needs of patients with ultra–rare, progressive neurological conditions. Early application of experimental therapies can provide opportunities for rapid clinical benefit assessment, though ethical and regulatory challenges persist. Real–world data gathered from such trials facilitate the “Fail Fast” approach, enabling timely discontinuation of ineffective or unsafe therapies.

While the United States has introduced frameworks that enable rapid experimental use of ASOs for ultra–rare diseases, Japan is also moving towards establishing similar systems through AMED–funded projects. Clinician involvement, multi–stakeholder collaboration, and robust ethical oversight will be crucial to ensure that individualized clinical trials can deliver safe and effective treatments to patients who lack other options, thereby expanding the frontiers of rare neurological disease therapy.