Osseni et al. (Brain, 2026) report that combining SMN2 splice modifiers (such as antisense oligonucleotides inducing exon 7 inclusion) with systemic HDAC6 inhibition strongly improved muscle strength, mass, function, and longevity in a SMA mouse model. HDAC6 is a class IIb histone deacetylase that controls tubulin acetylation — a critical regulator of myotube formation and maturation.

Key findings

• HDAC6 inhibition increased the size of muscle primary myotubes derived from SMA patients
• The benefit was strongest when combined with an SMN-restoring antisense oligonucleotide
• Effects were systemic — improving function across muscle groups, not just locally

Why this matters

New SMN-restoring gene therapies and splice modifiers have changed survival outcomes for SMA children. However, treated patients often face ongoing muscle atrophy and functional deficits even after SMN levels are restored. HDAC6 inhibition addresses this gap by acting on the muscle compartment directly, complementary to the SMN-restoring mechanism. Several HDAC6 inhibitors (such as ricolinostat / ACY-1215 and tubastatin A) are already in clinical development for other indications, opening potential repurposing pathways.

Source: Osseni et al., Brain 2026 (DOI: 10.1093/brain/awag148); SMA Europe May 2026 newsletter.