Key Clinical Summary: Latest Updates in Duchenne Muscular Dystrophy (DMD)

This is a micro-learning module summary of Dr Martina Sandona's DMD Academy session which you can find here.

Before participating please read our CME and disclosure information which can be found here.

The DMD Academy was supported by an independent medical education grant from ITF Therapeutics.

This content is intended for US Healthcare Professionals only.

Introduction

Corticosteroids remain standard of care in Duchenne Muscular Dystrophy (DMD) but alongside transient benefits they also have a troublesome toxicity profile. A diversified pipeline now targets upstream genetic defects (gene therapy, exon‑skipping) and down‑stream drivers of degeneration—fibrosis, inflammation, impaired regeneration. HDAC inhibitors (HDACi) sit in the latter category and have progressed from bench discovery to regulatory approval, adding a complementary option that does not rely on dystrophin restoration.

1 | Where We Stand in 2025 – A DMD Therapeutic Map

DMD care now spans three strategic tiers: restoring dystrophin, modulating downstream pathology, and supportive/organ‑specific protection. Key agents are summarised below to provide context before drilling into HDAC inhibitors.

Attempting to Replace or Repair Dystrophin, for instance:

AAV micro‑dystrophin gene transfer
Delandistrogene moxeparvovec – accelerated FDA approval 2023
Exon‑skipping strategy (mutation‑specific, weekly IV)
E.g. Eteplirsen, Golodirsen, Casimersen – FDA granted accelerated or conditional approvals

Modifying Pathogenic Cascades (Fibrosis, Inflammation, Regeneration), for instance

Corticosteroids – prednisone, deflazacort (FDA‑approved), cornerstone since 1990s.
Dissociative steroids – Vamorolone FDA‑approved 2023; retains efficacy with fewer bone/weight side‑effects.
HDAC inhibitors – givinostat now approved.
Utrophin modulators – ezutromid programme discontinued after phase‑2 futility; next‑gen compounds in discovery.

Take‑away: Treatment is increasingly layered. HDAC inhibitors add a mutation‑agnostic, anti‑fibrotic/regenerative tool that synergises with both up‑stream dystrophin‑restoring and standard steroid regimens.

2 | Mechanism of Action of HDAC Inhibitors

Epigenetic re‑programming: HDACi block class I/II HDACs, leaving chromatin open and transcription remaining active
Functional consequence: ↓ fibrosis & fat infiltration, ↑ myofiber regeneration, maintenance of contractile architecture.

3 | Key Clinical Evidence for Givinostat

Phase 1/2 dose‑finding study

Design & population: NCT01761292; 20 ambulant boys (19 boys completed the study), mean age 8.2y; open‑label

Key findings:

↑ Muscle Fiber Area Fraction (MFAF)
↑ myofiber cross‑sectional area (CSA).
↓ fibrosis, adipose infiltration and necrosis
Acceptable safety profile.

Clinical meaning: First human proof‑of‑concept that HDAC inhibition can modify DMD histopathology.

EPIDYS Phase 3 trial

Design & population: NCT02851797; 179 ambulant boys ≥ 6 y; double‑blind, 18 months; givinostat vs placebo (randomized 2:1).