New Era Of Gene Editing May Be On The Horizon

Personalized therapy

A big breakthrough is being hailed in the world of gene editing, with the first custom-designed treatment using CRISPR technology (CRSP). The therapy was developed for an infant named KJ Muldoon, who was born with a rare genetic disorder called carbamoyl-phosphate synthetase 1 (CPS 1). The condition prevents liver cells from breaking down proteins properly, resulting in an ammonia buildup that can lead to irreversible brain damage and possibly even death.

Snapshot: CPS 1 is typically treated with conventional methods, like protein restriction, nitrogen scavengers, and drugs to reduce ammonia, but the treatment may only be partially effective. A liver transplant can also be a solution, but patients have to be at least a year old and a donor has to be found. As a result, an experimental alternative was pursued, which delivered the CRISPR base-editing therapy using lipid nanoparticles.

A low dose was first given when KJ was only six months old, which was followed up by a higher intravenous infusion after careful monitoring. He just finished his third and final dose and seems to be responding well, with reduced blood ammonia concentrations and better tolerance to dietary protein. No serious adverse effects despite concurrent viral infections, and while it’s still early to know the full extent of things, doctors were able to halve the medication he receives to reduce ammonia in his body.

Watershed moment? While CRISPR (CRSP) is currently approved by the FDA to treat sickle-cell anemia and beta thalassemia, the treatments for those diseases rely on a one-size-fits-all approach. In contrast, KJ’s treatment was custom-tailored to his genetic makeup and brings hope that “on-demand” therapies of the future could be designed to fit an individual patient’s needs. The price tag for any gene editing therapy is still prohibitive (personalized therapy even more so), but the hope is that will change down the line as things move towards a platform-based approach. “As we get better at doing this, economies of scale will kick in, and you can expect the cost to come down orders of magnitude,” said lead researcher Dr. Kiran Musunuru of the University of Pennsylvania and the Children’s Hospital of Philadelphia.