Medicine› Neurology› Amyotrophic Lateral Sclerosis Research

Amyotrophic lateral sclerosis — Axon initial segment geometry of spinal motoneurones

Submitted 2026-10-22

Field: Medicine › NeurologyType: No effect foundArea: amyotrophic lateral sclerosisTarget: Axon initial segment geometry of spinal motoneuronesStage: preclinical

Hypothesis

Structural changes to the axon initial segment in presymptomatic ALS mice would impair motoneurones' ability to fire action potentials repetitively.

What failed

In adult presymptomatic G127X SOD1 mice, axon initial segments of alpha and gamma motoneurones were shorter (by 6.6% and 11.8%) and wider, yet in vivo intracellular recordings found no difference in single action potentials or in repetitive firing.

Broken assumption

A shorter axon initial segment necessarily reduces a neurone's excitability.

Why

The geometric change was real but had no detectable functional consequence within the normal working range of firing frequencies; the abstract does not say why.

From the published paper: Bonnevie et al. Scientific Reports, 2020. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

alsSOD1 antisensedifferent research area
Knocking down SOD1 expression via antisense oligonucleotide would slow motor neuron loss in SOD1-linked familial ALS.
CSF SOD1 protein dropped as expected, but functional decline (ALSFRS-R) tracked the untreated historical cohort.
Why it matched: shares SOD1 · mechanism: Synaptic & neuronal function

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.