What was reported

Coppejans, Vanhauwaert and colleagues (argenx, Edinburgh, Harvard) presented preclinical data at the 5th International Scientific Congress on SMA (Budapest 2026) on ARGX-119, a muscle-specific kinase (MuSK) agonist antibody, coadministered with SMN-C3 — a small-molecule SMN2 splicing modifier (SMN-C3 is the chemical parent of branaplam/risdiplam).

Mechanism

MuSK is the post-synaptic kinase at the neuromuscular junction. Together with LRP4, agrin and DOK7 it drives acetylcholine receptor clustering — the structural basis of voluntary muscle contraction. ARGX-119 is an agonist antibody (not blocker): it stimulates MuSK to strengthen NMJ formation and maintenance.

Preclinical findings (SMNΔ7 mouse model)

• ARGX-119 (10 mg/kg IP, PND 1, 21, 42) coadministered with SMN-C3 (3 mg/kg PND 1–20 IP, then 9 mg/kg PND 21–49 oral)
• At PND 21: ARGX-119–treated mice spent more time with both front paws up + improved lower front/hind luminance ratio + hind paw angle
• At PND 48: lower front/hind luminance ratio improvement persisted
• Masseter muscle force normalised to muscle weight: gain in ARGX-119 group

Why this matters

The data position ARGX-119 + splice modulation as a combination-therapy class. Even when SMN protein is restored by an SMN2 modulator, residual NMJ dysfunction limits functional recovery. A muscle-side intervention (ARGX-119) plus a neuron-side intervention (SMN-C3) addresses both halves of the disease.

ARGX-119 is investigational and Phase 1. This is a third-party preclinical report.