On this good-news Friday, I’d like to give you this link to our edition of Fix the News and focus my summary here on the world’s first personalized gene editing treatment.
There are 350 million people worldwide with rare diseases, most of which are genetic, says The Associated Press.
And while researchers have developed gene-editing therapies for illnesses that affect millions of people with common genetic mutations, like sickle cell disease, millions of others have genetic diseases with unique mutations that need personalized therapy, says The Wall Street Journal.
KJ Muldoon was a week old when he was diagnosed with a rare genetic disorder, CPS1 deficiency, that affects just one in 1.3 million babies.
Now nine and a half months old, he's the first patient of any age to have a custom gene-editing treatment, The New York Times reports. He's received an infusion made just for him and designed to fix his precise mutation.
The investigators who led the effort to save KJ presented their work Thursday at the annual meeting of the American Society of Gene & Cell Therapy and are publishing it in the New England Journal of Medicine.
The implications of the treatment go far beyond treating KJ, says Dr. Peter Marks, who was the Food and Drug Administration official overseeing gene-therapy regulation until he recently resigned over disagreements with Robert F. Kennedy Jr., secretary of health and human services.
More than 30 million people in the United States have one of more than 7,000 rare genetic diseases, and most are so rare that no company is willing to spend years developing a gene therapy that so few people would need.
But KJ’s treatment — which built on decades of federally funded research — offers a new way for companies to develop personalized treatments without going through years of expensive development and testing.
Illnesses like KJ’s are the result of a single mutation: an incorrect DNA letter among the three billion in the human genome.
Correcting it requires pinpoint targeting called base editing. The treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that tell the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed.
While KJ’s treatment was customized so CRISPR found just his mutation, the same kind of method could be adapted and used over and over to fix mutations in other places on a person’s DNA. Only the CRISPR instructions leading the editor to the spot on the DNA with the mutation would need to be changed.
Treatments would be cheaper, “by an order of magnitude,” says Dr. Marks. He wrote an editorial accompanying the research paper and says the method “is, to me, one of the most potentially transformational technologies out there.”
It eventually also could be used for more common genetic disorders such as sickle cell disease, cystic fibrosis, Huntington’s disease and muscular dystrophy.
Dozens of researchers put everything aside for months to work on KJ’s treatment, says the Times.
David Liu of Harvard, whose lab invented the gene-editing method used to fix KJ’s mutation, says the speed was “astounding. These steps traditionally take the better part of a decade, if not longer.”
The success in treating KJ “is a triumph for the American peoples’ investment in biomedical research,” says Dr. Fyodor Urnov of the University of California at Berkeley.
The work began decades ago with federal funding for basic research on bacterial immune systems. That led eventually, with more federal funding, to the discovery of CRISPR. Federal funding for sequencing the human genome made it possible to identify KJ’s mutation. Federal funding supported Dr. Liu’s lab and its editing discovery. A federal program to study gene editing supported other research. Federally funded work led to an understanding of KJ’s disease.
“I don’t think this could have happened in any country other than the U.S.,” Dr. Urnov says. And “we all said to each other, ‘This is the most significant thing we have ever done.’”