Alport syndrome is a rare genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. Most affected individuals experience progressive loss of kidney function, usually resulting in end-stage kidney disease. People with Alport syndrome also frequently develop sensorineural hearing loss in late childhood or early adolescence. The eye abnormalities characteristic of this condition seldom lead to vision loss.
An estimated 11,500 - 30,700 people have the disease1
Pediatric disease: Majority of patients diagnosed are under 18 years old. Median age at diagnosis of 9 to 20 years.2 Median time to kidney failure of 4 years to 12 years from diagnosis (Annualized eGFR2 change of -6.7 to -22.4 ml/min/1.73m2/year).
No approved disease modifying therapies exist for nonsense mutations.
Nonsense Mutation Alport syndrome is caused by mutations that cause premature stop codons in the mRNA in three possible genes: COL4A3, COL4A4, or COL4A5. These genes provide instructions that code for type IV collagen protein, which plays an important role in the glomeruli of the kidneys. Glomeruli are clusters of specialized blood vessels that remove water and waste products from the blood and create urine.
These collagen proteins are required for a healthy glomerular basement membrane and podoccyte foot processes that are essential for the kidneys to properly filter the blood. As a result, blood and protein pass into the urine. Over time, the kidneys become scarred, which leads to kidney failure.
Type IV collagen is also an important component of the Organ of Corti, the inner ear structure that transforms sound waves into nerve impulses for the brain. Alterations in type IV collagen may result in abnormal inner ear functions, which can lead to hearing loss.
In addition, type IV collagen plays a role in the eye, where it helps maintain the shape of the lens and the cells of the retina. Mutations found in Alport syndrome may affect the retina and the shape of the lens.
ELX-02 short-term in vitro readthrough and potential long-term impact
*Median age
References: 1. Kidney International website. 2020; 98, 1605–1614. 2. Alport syndrome. Medline Plus website. https://medlineplus.gov/ genetics/condition/alport-syndrome/#causes. Accessed April 5, 2022. 3. J Am Soc Nephrolv.28(6); 2017 JunPMC5461786 4. J Clin Invest 1995 Sep;96(3):1404-13