AAVrh10-PCCA Gene Therapy for Propionic Acidemia

Inclusion criteria

• Age six months to 2 years of age at day of vector infusion. For those <1 year of age they must have been ≥37 weeks gestational age at the time of birth and without other conditions/comorbidities that in the opinion of the Investigator may interfere with the interpretation of study results.
• Confirmed diagnosis of propionic acidemia with biallelic PCCA gene mutations based on molecular genetic testing.
• Study participants must have a diagnosis of neonatal-onset propionic acidemia with a documented episode of decompensation that can include any of the following findings: lethargy, poor feeding, irritability, vomiting, encephalopathy, respiratory failure, seizures, coma, metabolic acidosis, lactic acidosis, ketonuria, hypoglycemia, hyperammonemia, and cytopenias or history of recurrent hospitalizations.
• Parents or legal guardians of study participants must agree to comply in good faith with the conditions of the study, including attending all of the required baseline and follow-up assessments, and parents or legal guardians must give consent for their child's participation.

Exclusion criteria

• Hemoglobin <10 g/dl
• Platelet count < 100,000 per mm3
• Liver Enzyme ALT/AST >2.5 ULN
• Direct Bilirubin > 1.5
• Active viral infection (includes HIV or serology positive for hepatitis B or C).
• Previous liver transplant
• Subjects with active decompensation as demonstrated by a pH < 7.3, bicarbonate < 15 mmol/L, NH3 > 75 mcmol/L, lactate > 2.5 mmol/L, urine ketones
• Previously received gene therapy or messenger ribonucleic acid (mRNA) treatments for PA.
• Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification.
• Family does not want to disclose patient's study participation with primary care physician and other medical providers.