Innovative Gene Therapy: A New Hope for Rare Diseases

At the end of last year, the efforts of dozens of researchers across thousands of miles united in a race to save the life of a young child. The result was a world-first: an innovative gene therapy designed for a single individual, produced in a record six months.

Pioneering Clinical Trial

Now, the doctors of the child, KJ Muldoon, are preparing to replicate this achievement at least five more times and at a faster pace. The pioneering clinical trial, described on October 31 in the American Journal of Human Genetics, will use a gene-editing technique called CRISPR–Cas9 base editing, which allows scientists to make precise changes to the DNA sequence.

The study is expected to begin next year after regulators spent months negotiating with U.S. authorities on ways to streamline the complex path that gene therapy typically must take before entering trials.

Developing Personalized Treatment

The development of KJ’s treatment was “a stressful and intense six-month period,” says Dr. Kiran Musunuru, a cardiologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and one of KJ’s doctors. However, he believes it can be shortened.

The trial is the next step toward answering a question that has been on the minds of many families with children suffering from rare diseases since the news of KJ’s successful treatment spread: When will it be our turn?

Expanding Gene Therapy Use

In addition to the planned clinical trial in Philadelphia, the CRISPR Therapies for Children Center, launched in July at the University of California, Berkeley, and the University of California, San Francisco, is also aiming to develop personalized gene therapies. In September, the U.S. government’s Advanced Research Projects Agency for Health announced two programs to fund research in the development and manufacturing of “precision genetic medicine.”

“I am more optimistic now than I have been in the past,” says Joseph Hacia, a medical geneticist at the University of Southern California’s Keck School of Medicine in Los Angeles.

A Therapy Designed for One

In August of last year, shortly after KJ Muldoon was born, doctors realized he had a genetic mutation preventing him from producing the normal form of a vital liver enzyme called carbamoyl phosphate synthetase 1 (CPS1). This enzyme detoxifies ammonia, a natural waste product formed when the body breaks down protein.

However, one of KJ’s doctors, Dr. Rebecca Ahrens-Nicklas at the Children’s Hospital of Philadelphia, was working with Musunuru to develop a base-editing treatment that could be rapidly deployed to treat children with metabolic disorders.

Conclusion

Advancements in gene therapy indicate a brighter future for children with rare diseases. With techniques like base editing, personalized treatments can now be provided more quickly and effectively. If these efforts continue, they may represent a revolution in genetic medicine, offering hope and healing to many children and their families around the world.