An experimental therapy has saved the lives of 62 children affected by extremely cruel, a childhood genetic disease that weakens the defenses and facilitates all types of deadly infections: pneumonia, meningitis, chickenpox. The father of one of the girls, Jeff Nachem, details by phone the ordeal his family experienced a decade ago. “It was very hard. Our daughter Eliana had to be locked up at home, so my wife also isolated herself from the world so as not to risk infecting her. I had to continue going to work, but when I returned home I had to shower and put on clean clothes before touching them,” he remembers from New York. The revolutionary treatment is administered one day and that’s it, but it is so sophisticated that it can cost around . Eliana received it a decade ago and now leads a completely normal life. “He gets good grades at school, plays basketball and has even joined the school choir. It’s incredible,” summarizes his excited father.
The treatment consists of extracting, from the blood or bone marrow, the stem cells that are precursors of white blood cells, to introduce a healthy copy of the defective gene into them and return them corrected to the children. The results show 100% survival, after a follow-up that in five cases exceeded a decade. One of the leaders of the research, the American doctor, believes that it is still too early to say that they are cured. “For me, cure means absence of the disease throughout life. We cannot say that yet. However, the observation period already lasts between 7 and 12 years and the clinical benefits have remained completely stable, so I hope it will continue to be this way for life,” explains Kohn, from the University of California in Los Angeles, to EL PAÍS.
Up to five newborns suffer from the disease. Like other rare pathologies, its name is unpronounceable. ADA-SCID is the acronym for severe combined immunodeficiency due to a deficiency of adenosine deaminase, a protein essential for activating white blood cells, the body’s defenses. Due to the lack of this protein, the parents of the girl Eliana Nachem had to thoroughly disinfect anything that entered their house, while their daughter grew up without seeing the faces of her loved ones, covered by masks. The disease and others like it are popularly known as bubble boy syndrome, especially since the shocking film starring John Travolta in 1976.
Children no longer have to literally live in plastic bubbles like they did half a century ago, but isolation is still strict. “I remember how angry many people were when it started and they were asked to stay home for two weeks. People were going crazy for two weeks of confinement. Many of the families with this immunodeficiency have to be like this for years,” laments Jeff Nachem. To isolate their daughter from viruses, bacteria and fungi, Eliana’s parents had to relocate their pets to friends’ houses, do without plants, install filters to clean the air, and give up eating fresh fruits and vegetables. Without therapy, children often die before their second birthday.
Doctor Donald Kohn and his colleagues remind that current treatments have limitations and risks. It is possible to improve the defenses of these children with weekly injections of the missing protein, but in the long term the deadly infections return. Another option is a bone marrow transplant, but a compatible donor must be found quickly and there are often complications. And there is a third alternative: the , another gene therapy that has already saved a 4-year-old girl from Córdoba in Spain.
Strimvelis’s story encapsulates the nightmare that families affected by the disease have suffered. The treatment was born from research at the San Raffaele Hospital in Milan, developed together with the British pharmaceutical company GSK. This therapy also consists of introducing a healthy copy of the defective gene into children’s cells using a virus that acts as a carrier. The European Medicines Agency authorized Strimvelis in 2016 and GSK set a price of around 600,000 euros per patient. However, just two years later, the pharmaceutical company transferred to another company with headquarters in the United States and the United Kingdom, Orchard Therapeutics, which also ended up giving up marketing. The shortage of patients and the very high cost complicate the viability of these first gene therapies, even if they save lives. The system with rare diseases. For the moment, the Telethon Foundation, linked to the San Raffaele Hospital, has committed to maintaining the production of Strimvelis.
The immunologist took him to the Reina Sofía Hospital in Córdoba. In his opinion, the two gene therapies are “similar”, except for two relevant details. Strimvelis uses a retrovirus to introduce the healthy gene into cells. Its results in 43 children show an excellent efficacy and safety profile, but one of the patients developed unwanted alterations in DNA caused by the treatment itself. The new therapy from Donald Kohn’s laboratory uses another type of virus, lentivirus, and no indication of this problem has been detected. In addition, the Los Angeles team has managed to freeze the children’s cells after adding the gene, which will allow the treatment to travel and be administered in any hospital. Currently, families have to travel to Milan to receive Strimvelis, which consists of fresh cells. “They are slight improvements, but there are no differences enough to make us run away and discard one treatment and adopt another. In essence, these two gene therapies are comparable,” says Santamaría.
Doctor Donald Kohn says that the patent for his treatment belongs to the two institutions that developed it: the University of California in Los Angeles and University College London. The company Orchard Therapeutics also licensed the therapy in 2016, but stopped development five years later due to financial problems. Frustrated and with no partners in sight, Kohn and two members of his lab decided to found , the company that now holds the license to the patent. Kohn has also just received from a Californian agency to develop the industrial manufacturing of its therapy against ADA-SCID.
“I don’t know how much each treatment will cost,” says the American doctor. “It is complex to manufacture the cellular product for each patient, since it requires a facility with a clean room [un cuarto con limpieza extrema y atmósfera controlada]specialized technicians and rigorous quality control. Currently, patients typically receive protein injections for several years, which are also quite expensive. Therefore, a gene therapy that is administered only once should be more profitable after a few years,” reflects Kohn, who warns that he has shares of Rarity PBC. His latest results, in children treated in the United States or the United Kingdom, were announced this Wednesday in the specialized magazine.
Juan Antonio Bueren, former president of the European Society for Gene and Cell Therapy, collaborates with Kohn in that he has already saved the lives of a dozen children with another very rare disease, leukocyte adhesion deficiency type I (LAD-I). The Spanish researcher applauds the “terrific” results of the new study, but highlights the difficulties. “There is a problem for the commercialization of gene therapies for rare diseases: their cost right now is enormous, due to the cost of producing viruses and genetically modified cells, due to the cost of all the controls required by regulatory agencies and due to the fact that patients have to be followed for 15 years,” explains Bueren, from the Center for Energy, Environmental and Technological Research (CIEMAT), in Madrid.
Lentiviruses have already proven to be a potential cure for rare genetic diseases. They are some of the most expensive medicines on the planet. “As healthcare in the US is basically private, the price of this type of therapy amounts to four million euros and that’s it, but in Europe, where healthcare is eminently public, pharmaceutical companies encountered the problem that governments did not authorize such high costs. And many companies have no interest in developing gene therapies for rare diseases,” Bueren continues. Jeff Nachem, Eliana’s father, is clear: “I don’t know how much to charge for it, but this type of treatment should not be denied to a small child who needs it to survive.”
