“The most unlucky family in the world” : three brothers and sisters affected by a mortal rare genetic disease
When their eldest daughter Ava, only 8 weeks old, is hospitalized for the second time due to severe infection, Alicia and Jon Langenhop think of a coincidence. Then it is Olivia’s turn, their second daughter, to multiply colds, otitis and hospitalizations.
Alicia then worked as assistant director of a crèche, where her daughters are kept. Jon remembers: “We still accused the daycare. ” But after a visit to the dentist for AVA, whose gums were increasing abnormal, genetic examinations are launched. The diagnosis falls: Leukocyte Defertcy Type I Adhesion -LAD-I-A disease as rare as it is serious, affecting approximately one child out of a million in the world.
A mutation of the gene responsible for the CD18 protein prevents white blood cells from reaching infected areas: the immune system is paralyzed. Santed children must live in a bubble. Without treatment, most do not survive beyond childhood. The treatment is based on a marrow transplant, the success rate of which is around 75%. One of the hopes was that their new Landon child was compatible with one of the two. But he too had received the two copies of the defective genes from his parents, like his sisters. The probability that one of the children of Langenhop be reached by LAD-1 was 25 %. The probability for the three children was approximately 1.5 %.
“”It is said that around one in one million is affected by LAD-1 “said Alicia. “”I was speechless. I was incredulous at the idea that all babies suffer the same thing. ”
“We really felt like the most unlucky family in the world.”
The family then seeks to draw ‘attention to the media to find compatible marrow donors, which draws the attention of Dr Donald Kohn from the UCLA.
Gene therapy succeeds in re -educating their immune system
Donald Kohn is launching a new genre clinical trial. Unlike bone marrow transplants, which require a compatible donor and include risks of rejection, the proposed approach is based on a Genetic correction of patient cells himself.
The principle of this treatment developed by Rocket Pharmaceuticals? Take blood stem cells, correct them in the laboratory using a lenty vector – An harmless virus which inserts a functional copy of the CD18 gene – then reinject these cells so that they produce white blood cells capable of locating infections.
“That’s the idea of gene therapy: the patient becomes his own donor. It is perfect compatibility”, explains Dr. Kohn.
Before reinjection, gentle chemotherapy cleans the bone marrow to make room for new cells. Once grafted, the latter produce lasting functional immunity. “Once the gene is integrated, it’s permanent”, specifies Kohn.
The results are spectacular. The treated children show normal CD18 protein levels, a return to a normal leukocyte number and, above all, a disappearance of serious infections. No major side effects have been observed.
“These children are no longer defined by their diagnosis. Seeing them in good health, without serious infections or frequent hospitalizations, proves how beneficial this therapy is.” underlines Kohn.
“We avoid using the word healed, because we can only say it after a whole life without relapse. But we hope with all my heart.”
A future found for Ava, Olivia, Landon … and many other children
Today, children Langenhop lead a normal life. They go to school, play in the snow … “It’s magic. It’s incredible”, Judge Donald Kohn. No more antibiotic treatments three times a day, repeated hospitalizations, constant fear. Their mother sums up this new daily life simply: “Before, I was a panic mother. Now I’m just a happy mother.”
From now on, the brothers and sisters are getting closer to shared memories of their journey, testimonies of resilience and hope. “They went through so many things together. It made them stronger,” Add Alicia.
In total, nine patients benefited from this treatment. All have replied well and no longer have any symptoms. Their skin lesions and their highly inflamed gums, characteristic of the disease, have disappeared. They are now able to fight infections like their comrades born with a healthy immune system.
© Ucla Broad Stem Cell Research Center/Great Ormond Street Hospital
This therapy is now under examination by the American health authorities. If it is approved, it could become Reference treatment for LAD-Iand pave the way for other curative treatments for similar genetic diseases.