Nonsense Mutation Alport Syndrome (NMAS)
A rare inherited kidney disease where a nonsense mutation in COL4A3, COL4A4, or COL4A5 prevents production of functional Collagen IV. Eloxx is advancing exaluren in the EXACT Phase 2b study.
Understanding NMAS
Alport syndrome is caused by mutations in the COL4A3, COL4A4, or COL4A5 genes, encoding the alpha chains of Collagen IV — the structural protein of the glomerular basement membrane. In patients with nonsense mutations, a premature stop codon prevents full-length Collagen IV production, disrupting the kidney's filtration barrier.
The result is progressive podocyte injury, hematuria, proteinuria, and kidney failure — typically in a patient's 20s or 30s. Nonsense mutations carry a more severe prognosis than missense mutations. No FDA-approved therapy addresses the genetic cause.
Normal kidney filtration versus Collagen IV loss in nonsense mutation Alport syndrome.
Savige et al. 2022, Kidney Int — mean age at kidney failure in NMAS: 20.4 ± 5.0 years.
Yamamura et al. 2020, Nature Communications — Collagen IV restoration improved GBM integrity and kidney survival in Alport mouse models.
Living with Alport syndrome
If you or a loved one has Alport syndrome with a known nonsense mutation, here is how to learn more and find support.
EXACT Study — Alport syndrome clinical trial
Eloxx is conducting the EXACT Phase 2b randomized study evaluating exaluren in people with Alport syndrome caused by confirmed nonsense mutations in COL4A3, COL4A4, or COL4A5. Speak with your nephrologist or a genetic kidney disease specialist if this may be relevant to you.
Patient advocacy & support
The Alport Syndrome Foundation provides community, resources, and specialist connections for people living with Alport syndrome and their families.
Study design & referral
For study design, eligibility criteria, and referral pathways for the EXACT Phase 2b study in nonsense mutation Alport syndrome, visit the EXACT Study Information page or the official ClinicalTrials.gov record.