Nephropathic cystinosis is a rare disease affecting infants who inherit two mutant copies of the CTNS gene, causing accumulation of cystine in all tissues. At birth, babies appear normal, but growth is impaired by 4 to 6 months and important nutrients leak into the urine. Without treatment, dialysis and transplantation are required by age 10. Other organs deteriorate in the teenage years. In young adults, the muscles, brain and heart are affected and survival beyond 30 years is rare. Current treatment, cysteamine, can delay (but not prevent) renal failure.
In Québec, cystinosis is more common due to a special (“Nonsense”) mutation in the CTNS gene (W138X) introduced into the French Canadian population by an Irish immigrant. Nonsense mutations instruct the cell to stop production of CTNS protein before it is finished. Certain antibiotics (aminoglycosides) can trick the cell to bypass a Nonsense mutation, but are generally too toxic to be used as long-term therapy. In recent years, Eloxx Pharmaceuticals has designed a novel aminoglycoside (ELX-02) that is much less toxic. Studies at McGill University showed that ELX-02 bypasses the W138X mutation in patient cells and shows no toxicity in cells, animals and human volunteers. By restoring production of the normal CTNS protein, sustained ELX-02 therapy has the potential to be curative.
Eloxx Pharmaceuticals is now partnering with the laboratory of Dr. Paul Goodyer to screen North Americans for CTNS Nonsense Mutations and then move to a Phase II clinical trial. If the trial proves successful, ELX-02 could save up to 5.2 million in the case of cystinosis and would set a precedent for a broad application in other genetic diseases caused by Nonsense Mutations.