The baby KJ had a devastating genetic disorder, CPS1 deficiency. Half of all babies with the disorder die in their first week. Even if he survived, he would suffer severe mental and developmental delays and eventually require a liver transplant. But gene-editing has saved his life:
KJ has made medical history. The baby, now 9 ½ months old, became the first patient of any age to have a custom gene-editing treatment, according to his doctors. He received an infusion made just for him and designed to fix his precise mutation….The implications of the treatment go far beyond treating KJ…More than 30 million people in the United States have one of more than 7,000 rare genetic diseases. 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…offers a new path 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 in an approach called base editing.
To accomplish that feat, 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 command the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — which was 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 sort of method could be adapted and used over and over again 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 at least.”
Earlier, gene therapy ended the years of excruciating pain suffered by Kendric, a boy with sickle cell disease. His life was “punctuated by episodes of excruciating pain, requiring days in the hospital as doctors tried to control it. Sickle cell eroded his hip bones. It prevented him from riding a bike or playing soccer or even going outside when the temperature was below 55 degrees Fahrenheit because cold often brought on intense pain.” But sickle cell gene therapy is not easy: “The treatment is labor intensive, requiring patients to spend at least a month in the hospital…large medical centers said they could treat only 10 or fewer [patients] per year, and some say they can treat just five or six.”
NBC reported that sickle cell gene therapy’s approval came
a decade after the discovery of CRISPR technology for editing human DNA, representing a significant scientific advancement….Casgevy, co-developed by Vertex Pharmaceuticals and CRISPR Therapeutics, uses Nobel Prize-winning technology CRISPR to edit a person’s genes to treat disease. The treatment was approved by U.K. regulators last month….. Casgevy uses CRISPR to make an edit to a person’s DNA that turns on fetal hemoglobin, a protein that normally shuts off shortly after birth, to help red blood cells keep their healthy full-moon shape. In clinical trials, Casgevy eliminated pain crises in most patients. The FDA approved the treatment for people 12 years and older…
While the treatment itself is administered only once, the whole process takes months. Blood stem cells are extracted and isolated before being sent to Vertex’s lab, where they’re genetically modified. Once ready, patients receive chemotherapy for a few days to clear out the old cells and make room for the new ones. After the new cells are infused, recipients spend weeks in the hospital recovering. Vertex will take the lead on launching the drug and estimates about 16,000 people with severe cases of sickle cell will be eligible….Because the procedure is so complex, it will be limited to certain health facilities like academic medical centers. Nine health-care facilities are ready to start administering Casgevy, Vertex said in a release, with more facilities added in the coming weeks….
The FDA can take many years to approve new drugs and therapies. The FDA didn’t approve a home test for HIV until 24 years after it first received an application. According to an FDA advisory committee, the test held “the potential to prevent the transmission of more than 4,000 new HIV infections in its first year of use alone.” That means thousands of people likely got infected with AIDS as a result of the delay in approving it. At least a hundred thousand people died waiting years for the FDA to approve beta blockers.
