Medicine› Neurology› Amyotrophic Lateral Sclerosis Research

ALS — C9orf72 repeat RNA

Submitted 2026-10-18

Field: Medicine › NeurologyIllustrative exampleArea: alsTarget: C9orf72 repeat RNAStage: phase 1✦ AI inferred reasoning

Hypothesis

Intrathecal antisense against the C9orf72 repeat expansion would lower dipeptide repeat protein throughout the CNS.

What failed

Poly(GP) fell sharply in lumbar CSF but post-mortem cortex from two participants showed near-baseline levels.

Why

Insufficient exposure above the cervical cord — intrathecal delivery did not achieve tissue distribution to the motor cortex, so the hypothesis was never actually tested there.

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).

Not available for example entries: this one describes an invented experiment, and ideas built on it would be fiction.

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 antisense
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: same research area · mechanism: Gene expression & RNA

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.