Menduti et al. (Experimental and Molecular Medicine, 2026) report that haloperidol — a D2 dopamine receptor antagonist FDA-approved since 1967 for psychosis — induces neuroprotection and enhances neuromuscular function in both murine and human SMA models.

A familiar molecule, a new target

Haloperidol's primary mechanism in psychiatric use is D2 dopamine antagonism, but it also binds the sigma-1 receptor (SIGMAR1). Sigma-1 receptor agonism is a known neuroprotective mechanism — Pridopidine, a selective sigma-1 agonist, is in late-stage clinical trials for amyotrophic lateral sclerosis (ALS).

Why repurposing matters

Haloperidol is off-patent, inexpensive, widely available, and has decades of clinical safety data. Repurposing such a molecule for SMA neuroprotection — if validated in human trials — could provide a low-cost adjunct to SMN-restoring therapies and accelerate access in regions where newer drugs remain prohibitively expensive. The findings reinforce a broader trend in SMA research toward non-SMN-restoring complementary mechanisms (alongside HDAC6 inhibition and JNK inhibition reported elsewhere).

Caveats

These results are from preclinical models. Haloperidol has notable side effects including extrapyramidal symptoms, particularly with chronic use — so any clinical translation would require careful dose-finding, ideally targeting dose ranges far below psychiatric use. No human trial of haloperidol in SMA has been registered to date.

Source: Menduti et al., Exp Mol Med 2026; SMA Europe May 2026 newsletter.