Altering neuronal circuitry with 4-aminopyridine for visual improvement in Leber's hereditary optic neuropathy (LHON)

Mitochondrion. 2022 Jan;62:181-186. doi: 10.1016/j.mito.2021.12.003. Epub 2021 Dec 13.


In this retrospective, interventional, longitudinal small case series, we looked at the visual effects of pharmacologic intervention with 4-aminopyridine (4-AP) in chronic Leber's Hereditary Optic Neuropathy (LHON) patients who are non-responders to idebenone. We illustrate, as examples, the visual progression of three LHON patients with 4-AP as add-on therapy to idebenone. Each patient had a different primary LHON mutation and was treated with idebenone within one year of onset. No response to idebenone at 300 mg orally three times a day ranged from less than one year to 2.5 years, and the addition of 4-AP at 10 mg orally two times a day ranged from 24 to 29 months. Outcome measures included best-corrected distance visual acuity, color vision, automated perimetry, the average retinal nerve fiber layer (RNFL) thickness, and the full-field photopic negative response (PhNR) amplitude. The 19-year-old man with the LHON mutation 11778A > G had no response to the addition of 4-AP to idebenone. The 27-year-old man with the LHON mutation 3460A > G experienced a significant response to 4-AP. Finally, the 40-year-old man with the LHON mutation 14484 T > C had a milder response. Although this case series was too small to demonstrate the efficacy of idebenone with add-on 4AP, it allowed us to consider a new hypothesis that neuronal activity generated from 4-AP can add more potential for visual recovery in LHON patients.

Keywords: 4-Aminopyridine; Idebenone; Leber’s hereditary optic neuropathy (LHON); Neuroenhancement; Neuronal activity.

Publication types

  • Case Reports

MeSH terms

  • 4-Aminopyridine / administration & dosage
  • 4-Aminopyridine / therapeutic use*
  • Adult
  • DNA, Mitochondrial / genetics
  • Drug Therapy, Combination
  • Humans
  • Male
  • Nerve Net / drug effects*
  • Neurons / drug effects*
  • Optic Atrophy, Hereditary, Leber / drug therapy*
  • Retrospective Studies
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / therapeutic use
  • Young Adult


  • DNA, Mitochondrial
  • Ubiquinone
  • 4-Aminopyridine
  • idebenone