Arimoclomol (Miplyffa) & Levacetylleucine (Aqneursa) for Niemann‑Pick Type C
Arimoclomol, approved by the FDA in September 2024, acts as a molecular chaperone to reduce protein aggregation and slow neurodegeneration in Niemann‑Pick disease type C (NPC). Levacetylleucine (Aqneursa), also approved in September 2024, showed improvement in neurologic symptoms—such as motor function and quality of life—during clinical trials involving NPC patients. It’s also being studied for Tay‑Sachs, Sandhoff, Ataxia‑Telangiectasia, ALS, and other disorders.
These approvals represent the first-ever drug therapies for NPC and highlight a growing trend toward repurposing small molecules in rare neurological disease.
Emerging Pipelines: Epilepsies, Rett & Fragile X
Dravet Syndrome: Zorevunersen
Stoke Therapeutics and Biogen are developing zorevunersen, an RNA-based therapy targeting severe childhood epilepsy. Global Phase III trials begin mid‑2025, aiming for data release by late 2027. The drug has been expedited via FDA and EMA designations.
Rett Syndrome & Fragile X: Computation-Led Drug Discoveries
Neurolixis is developing NLX‑112 for Spinocerebellar Ataxia, and NLX‑101 for both Fragile X Syndrome and Rett Syndrome. Initial preclinical data show improved cognition, mood, and motor function in animal models.
Separately, researchers at the Wyss Institute identified vorinostat, via advanced gene‑network modelling (nemoCAD), as a promising therapy for Rett syndrome. In CRISPR-engineered tadpoles and mouse models, it reversed seizures, motor and GI symptoms—even when administered after full disease onset—and outperformed trofinetide in preclinical efficacy.
Real‑World Case Highlights
QALSODY (tofersen) for SOD1 ALS
Approved by the FDA, tofersen targets the rare SOD1 mutation in familial ALS. One notable patient halted disease progression within months of treatment, regaining mobility and function—demonstrating that targeted genetic therapy can deliver clinical reversal in rare neurodegenerative disorders.
Experimental CoQ10-stimulating Therapy in HPDL-related Mitochondrial Disease
An 8-year-old with a fatal HPDL mutation received oral 4‑HB compound to boost CoQ10 synthesis. Within weeks, he regained walking ability and energy, showing striking early results with no adverse effects reported. While still experimental, the outcome offers a rare glimmer of success in severe mitochondrial neurological disease.
CHAPLE Disease & Pozelimab in India
A rare CD55-deficiency disorder affecting fewer than 100 people globally was treated in a child in Gujarat with monoclonal antibody pozelimab. Though not curative, the 24-week injection regimen aims to halt severe protein-losing enteropathy and show recovery—underscoring global collaboration and access to ultra-orphan drugs in low-resource settings.