Apr 18, 2019

Study: "Bubble boy" disease has been cured

Gael Jesus Pino Alva, a 2-year-old treated with gene therapy, with his mother, Giannina Alva. Photo: Peter Barta/St. Jude

Scientists announced that they have "cured," at least for the near-term, the rare genetic disorder that causes a male baby to be born with little or no immune system, or what's commonly known as the "bubble boy disease."

Why it matters: It's estimated that only 40–100 babies are born yearly with this disorder, but almost all of them died within 2 years unless they were diagnosed and placed into sterile environments, like those dramatized in movies and real documentaries. The study, published on Wednesday in the New England Journal of Medicine, says the therapy already has helped a couple of the toddlers enough to play like healthy children and even enter day care.

Background: X-SCID (X-linked severe combined immunodeficiency) is a life-threatening genetic disorder male babies can get if there's a mutation in a gene on the X chromosome called IL2RG.

  • Babies born with SCID have no defense against germs — even the common cold can be deadly.
  • Currently, the most effective treatment is to find a bone marrow match, preferably from a sibling, and transplant stem cells. This works particularly well if done in the first 3 months of a child's life, but it is very difficult to find a match.
  • Because gene therapy is relatively new, scientists consider diseases with mutations in single genes, like SCID, to be prime candidates. However, it's still experimental, so this trial was only done on children without a bone marrow match.
  • Prior therapies had mixed results (they only produced one type of immune cell) or were halted after causing leukemia, likely resulting from the different vector that transports the new gene to the cell.
  • But before this study, the National Institutes of Health tested a treatment using a new lentivirus vector on 5 older SCID patients with promising early results.

What they did: St. Jude Children's Research Hospital, which led the study and co- developed the new lentivirus vector with NIH, used a novel approach to the therapy combining the new vector and a low dose of chemotherapy.

  • The new lentivirus vector was engineered from a de-activated HIV virus and includes insulators to block activation of genes adjacent to the insertion to prevent leukemia.
  • They selected 8 children, ages 2 months to 14 months without donor matches, and collected their bone marrow, inserted the gene in the lab, and froze it while they did quality testing.
  • Before having it reinfused, the infants received 2 days of low-dose busulfan chemo to make space for the new bone marrow cells to grow.

What they found: James Downing, president and CEO of St. Jude, said in a press conference that the trial had "outstanding results" with children "responding to vaccines and able to live normal lives."

  • Most patients were discharged from the hospital within 1 month, and within 3 months, immune cells were present in the blood of all but 1 patient, who required a second dose of gene therapy.
  • Study co-author Ewelina Mamcarz said in a press conference that they were thrilled to see the development of all 3 main types of immune cells: T-cells, B-cells and natural killer cells.
  • 4 infants were able to discontinue intravenous immunoglobulin treatment that give additional antibodies to boost immunity. And 3 of the 4 developed normal antibody responses to normal vaccinations — an indication of robust B-cell function, she said.
  • While acknowledging that it is rare in the scientific community to claim a "cure," Mamcarz says, "They are cured because for the first time we were able to restore all three cells that constitute the immune system."
  • There was no early indication of leukemia up to 2.5 years after the first treatment, she adds. However, the authors said, the children will be closely monitored to see how durable the cure will be.

What they're saying: Rebecca Hatcher Buckley, immunology professor at Duke University School of Medicine who was not part of this study, says the vector in particular is "very promising," particularly as the treatment so far has not produced leukemia.

  • However, she says right now it's not clear they will all have robust B-cell functions and the children will need to be watched for side effects from the chemo, such as possible infertility.
  • "Compared with previously tested gene-therapy strategies for X-SCID, which used other vectors and chemotherapy regimens, the current approach appears safer and more effective," NIH said in a press release.

What's next: The trial is ongoing and St. Jude has signed an exclusive license with Mustang Bio to determine the best strategy to commercialize the immunotherapy for other genetic disorders, possibly including sickle cell disease.

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Trump touts press briefing "ratings" as U.S. coronavirus case surge

Photo: Drew Angerer/Getty Images.

President Trump sent about a half-dozen tweets on Sunday touting the high television ratings that his coronavirus press briefings have received, selectively citing a New York Times article that compared them to "The Bachelor" and "Monday Night Football."

Why it matters: The president has been holding daily press briefings in the weeks since the coronavirus pandemic was declared, but news outlets have struggled with how to cover them live — as Trump has repeatedly been found to spread misinformation and contradict public health officials.

World coronavirus updates: Total cases surge to over 700,000

Data: The Center for Systems Science and Engineering at Johns Hopkins, the CDC, and China's Health Ministry. Note: China numbers are for the mainland only and U.S. numbers include repatriated citizens and confirmed plus presumptive cases from the CDC

There are now than more than 700,000 confirmed cases of the coronavirus around the world, according to data from Johns Hopkins. The virus has now killed more than 32,000 people — with Italy alone reporting over 10,000 deaths.

The big picture: Governments around the world have stepped up public health and economic measures to stop the spread of the virus and soften the financial impact. In the U.S., now the site of the largest outbreak in the world, President Trump said Saturday he would issue a "strong" travel advisory for New York, New Jersey and parts of Connecticut.

Go deeperArrowUpdated 45 mins ago - Health

Coronavirus dashboard

Illustration: Sarah Grillo/Axios

  1. Global: Total confirmed cases as of 2 p.m. ET: 704,095 — Total deaths: 33,509 — Total recoveries: 148,824.
  2. U.S.: Leads the world in cases. Total confirmed cases as of 2 p.m. ET: 132,637 — Total deaths: 2,351 — Total recoveries: 2,612.
  3. Federal government latest: The first federal prisoner to die from coronavirus was reported from a correctional facility in Louisiana on Sunday.
  4. Public health updates: Fauci says 100,000 to 200,000 Americans could die from virus.
  5. State updates: Louisiana governor says state is on track to exceed ventilator capacity by end of this week — Cuomo says Trump's mandatory quarantine comments "really panicked" people
  6. World updates: Italy on Sunday reported 756 new deaths, bringing its total 10,779. Spain reported almost 840 dead, another new daily record that bring its total to over 6,500.
  7. What should I do? Answers about the virus from Axios expertsWhat to know about social distancingQ&A: Minimizing your coronavirus risk
  8. Other resources: CDC on how to avoid the virus, what to do if you get it.

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