Gene Therapy for Propionic Acidemia

This trial tests a new gene therapy for propionic acidemia, a serious genetic disorder causing symptoms like vomiting, tiredness, and cognitive impairment due to toxic build-up in the body. The trial evaluates whether this therapy can safely reduce these issues. Participants will receive one of three different doses of AAVrh10-PCCA gene therapy to determine the most effective dose. Ideal candidates are young children diagnosed with propionic acidemia, particularly those with severe symptoms since birth. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Research has shown that gene therapies using AAV, like the one tested for propionic acidemia, have been safe in earlier studies. In mice, delivering the PCCA gene with AAV resulted in long-term safety and improved survival rates, indicating the treatment was well-tolerated over time.

Unlike the standard of care for propionic acidemia, which typically involves dietary management and medications to reduce ammonia levels, AAVrh10-PCCA gene therapy offers a groundbreaking approach by directly addressing the genetic root of the condition. This therapy uses an adeno-associated virus (AAV) to deliver a functional copy of the PCCA gene directly into the patient's cells. By doing so, it potentially corrects the enzyme deficiency responsible for the disorder. Researchers are excited because this gene therapy could provide a long-term solution with just a single dose, offering hope for improved quality of life for patients.

Research has shown that a type of gene therapy called AAVrh10-PCCA could help treat propionic acidemia. In studies with mice, this therapy delivered the PCCA gene, extending their lifespan and improving symptoms. The treatment addresses the genetic issue causing the disorder, enabling the body to properly break down certain fats and proteins by correcting the function of a crucial enzyme. These early results suggest that AAVrh10-PCCA might correct the enzyme deficiency responsible for the harmful buildup of toxic substances in people with propionic acidemia. While these findings are promising, further research is needed to confirm these effects in humans. In this trial, participants will be divided into three cohorts, each receiving a different dose of AAVrh10-PCCA to evaluate its safety and effectiveness.¹²³⁴⁵