What was reported

Gerstner, Wittig, Menedo, Ruwald, Sumner, Mentis, Pellizzoni and colleagues (Leipzig, Columbia, Johns Hopkins, Ulm, DZNE) reported at the 5th International Scientific Congress on SMA (Budapest 2026, oral O36) that cerebellar Purkinje cell (PC) degeneration intrinsically contributes to motor + cognitive deficits in SMA.

A separate poster from the same Leipzig group (Sayan Ruwald, Poster Session 1 winner) addressed divergent therapeutic effects of risdiplam vs AAV9-SMN on cerebellar pathology in severe SMA mice.

Findings

• Conserved cerebellar circuit pathology with progressive PC degeneration in a severe SMA mouse model + Type I SMA patients
• Synaptic loss + dysfunction of parallel fibers onto PCs → reduced functional output of cerebellar cortex
• These impairments arise intrinsically within the cerebellum, independent of established spinal motor circuit pathology
• PC-specific Smn knockdown alone (Cre-dependent) caused severe progressive PC degeneration + severe motor impairment
• PC loss produced cognitive impairment (severe reduction in ultrasonic vocalisations); partially rescued by PC-selective SMN restoration

Why this matters

The cerebellum has been treated as a secondary site in SMA. These data position it as a first-class disease compartment — explaining persistent cognitive symptoms reported by older patients and clinical-class divergence between SMN-restoring drugs that distribute differently to cerebellum (intrathecal ASO, oral risdiplam, AAV9 gene therapy).

Evaluation of cerebellar-specific endpoints — vocalisation, fine motor coordination — may need to enter SMA outcome measure batteries.

This is a Congress oral; the full-paper publication is anticipated. Third-party report.