Advancing RNA Therapies in Neuromuscular Disease
RNA-based therapeutics, including antisense oligonucleotides (ASOs), are revolutionizing the treatment of genetically driven neuromuscular diseases such as Amyotrophic Lateral Sclerosis (ALS) and Duchenne Muscular Dystophy (DMD). By targeting disease-causing mutations at the RNA (transcript) level, ASOs can restore protein expression, correct splicing defects, or silence toxic gene products, offering genuine disease-modifying potential.
Landmark advances, such as the FDA approval of nusinersen (Spinraza) for SMA in 2016 and tofersen for ALS in 2023 (targeting SOD1), have shown what’s possible. But with these milestones comes a new set of challenges like efficient delivery, tissue-specific uptake, and in situ validation of therapeutic engagement, especially in complex tissues like motor neurons and skeletal muscle.
Tracking and Validating RNA Therapeutics In Situ
The next wave of RNA drug development depends on tools that allow researchers to track therapeutic engagment at the molecular level. A 2023 Science study showed that restoring STMN2, a protein depleted by TDP-43 dysfuction, can rescue axonal regeneration in ALS models using ASO-based intervention.1 This positions STMN2 as both a mechanistic biomarker and a quantifiable readout for ASO efficacy.
Similarly, a 2025 Nature study underscored the importance of intracellular trafficking in determining ASO efficacy. Using a genome-wide CRISPR screen, researchers identified endosomal transport regulators that dramatically enhanced RNA drug bioavailability in disease-relevant tissues.2
These insights highlight the need for tools that go beyond transcript-level measurement and enable in situ validation:
- Confirm ASO uptake in affected tissues
- Quantify target protein modulation
- Visualize ASO localization at cellular and subcellular levels
Tools for the RNA Therapeutics Workflow
Rockland and antibodies-online support the neuromuscular disease research community with a suite of targeted antibodies against key ASO targets in ALS and DMD. In addition, ModDetect™ is a novel platform for detecting chemically modified ASOs in cells and tissues without the need for fluorescent tags and allows researchers to directly visualize and quantify ASO distribution and engagement.
Together, these tools help bridge the gap between molecular drug design and measurable biological effect, accelerating the translation of RNA-based therapies.
ALS-related Targets
| Product | Target | Relevance | Applications |
| Anti-TDP43 | TARDBP | Hallmark of RNA-binding portein mislocalized in ALS | WB, IHC, ICC |
| Anti-SOD1 | SOD1 | Mutated in familial ALS, target of approved ASO therapy (Tofersen) | WB, IHC, ICC |
| Anti-C9ORF72 | C9ORF72 | Most common genetic ALS mutation; key ASO target | |
| Anti-STMN2 | STMN2 | Key ASO efficacy readout downstream of TDP-43 dysfunction | WB, IHC, ICC |
| Anti-Neurofilament L | NEFL (NF-L) | Biomarker of axonal damage; used as a clinical endpoint in trials | WB, IHC |
| Anti-EAAT2 | SLC1A2 (EAAT2) | Excitotoxicity regulator; target of neuroprotection strategies | WB, IHC |
| Anti-SQSTM1/p62 | SQSTM1 (p62) | Aggregation and autophagy marker, ALS biomarker | WB, IHC |
| Anti-Nogo-A | RTN4 (Nogo-A) | Inhibitor of axonal regeneration; ALS and neurotrauma models | WB, IHC |
DMD-related Targets
| Product | Target | Relevance | Application |
| Anti-Dystrophin | Dystrophin | Gold-standard marker for ASO rescue of DMD expression | WB, IHC |
| Anti-Utrophin | Utrophin | Functional dystophin analog; upregulation supports muscle integrity | WB, IHC, ICC |
| Anti-MSTN | MSTN (Mystatin) | Inhibitor of muscle growth; suppression is a therapeutic strategy | WB, IHC |
| Anti-CTGF | CTGF | Pro-fibrotic marker upregulated in DMD; monitors muscle healing response | WB, IHC |
| Anti-VDAC1 | VDAC1 | Marker of mitochondiral dysfunction in dystrophic muscle | WB, IHC, ICC, IF |
| HDAC1-10 | HDACs | Epigenetic regulators; HDAC inhibiton may enhance regeneration | WB, IHC |
| Anti-TGFB1 | TGF-β1 | Master regulator of fibosis; often used alongside CTGF | WB, ELISA, IHC |
| Anti-CD68 | CD68 | Macrophage infiltration marker; tracks inflammation and immune response | WB, IHC |
References
- Michael W. Baughn et al. ,Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science 379, 1140-1149 (2023).
- Malong, L., Roskosch, J., Hager, C. et al. A CRISPR/Cas9 screen reveals proteins at the endosome-Golgi interface that modulate cellular anti-sense oligonucleotide activity. Nat Commun 16, 5378 (2025).