Treatment for Restoring Ureagenesis in Carbamoyl Phosphate Synthetase 1 Deficiency
Tech ID: 30356 / UC Case 2019-600-0
SUMMARY
UCLA researchers in the Department of Surgery have developed a gene therapy to treat carbamoyl phosphate synthetase 1 deficiency.
BACKGROUND
Carbamoyl phosphate synthetase 1 (CPS1) deficiency is an inherited autosomal recessive urea cycle disorder characterized by complete or partial loss of CPS1 enzyme. The urea cycle cannot proceed normally in the absence of CPS1, and nitrogen accumulates in the form of ammonia in the bloodstream. Ammonia is especially damaging to the nervous system and can cause neurological problems. Complete lack of CPS1 results in the severe form of the disorder, and the symptoms may occur within 24-72 hours after birth, regardless of exposure to dietary protein. An infant with the severe form of CPS1 deficiency may experience seizures, abnormal body movements, and respiratory distress that are mostly attributable to the swelling of the brain caused by hyperammonemia. The disorder may potentially result in neurological abnormalities, including developmental delays and intellectual disability. Patients with the milder form of CPS1 deficiency show symptoms later during infancy, childhood, or adulthood, and they also experience hyperammonemic coma and life-threatening complications. Current treatment for CPS1 deficiency consists primarily of dietary protein restriction, which is only marginally effective and leaves patients vulnerable to recurrent hyperammonemia and progressive, irreversible neurological decline.
INNOVATION
Researchers at UCLA have developed a gene therapy that replenishes codon optimized CPS1 enzyme in the body for treating CPS1 deficiency.
APPLICATIONS
Gene therapy for carbamoyl phosphate synthetase 1 deficiency
ADVANTAGES
The described gene therapy overcomes the limit of packing large cDNA into adeno-associated viral vectors
STATE OF DEVELOPMENT
The described gene therapy has been validated in a conditional CPS1 knock out mouse model.