An experimental treatment against hereditary anemia prevents young people from being dependent on injections of red blood cells to survive.
Cure congenital diseases correcting DNA defects of patients is a reality more and more palpable. Last year, the United States approved its first gene therapy to combat acute lymphoblastic leukemia in young people. Now, another treatment of this experimental type has corrected beta thalassemia, one of the most common hereditary anemias.
Thalassemia is due to a mutation in the HBB gene that affects the production of hemoglobin, the protein responsible for transporting oxygen to organs and tissues. Beta thalassemia, which affects one in 100,000 births, is the most serious variant and requires blood transfusions every few weeks from infancy, which in turn causes problems due to the accumulation of iron in the blood.
The new treatment involves removing hematopoietic stem cells from the patients’ bone marrow and injecting LentiGlobin, a drug based on an inactivated version of HIV that contains a small DNA sequence. The virus enters the stem cells of the patients and adds that sequence to the HBB gene to correct the defect that causes the disease.
The patients first received a chemotherapy session to avoid rejection and then a single injection with their own already corrected stem cells. Of the 22 patients between 12 and 35 years in the US, France, Thailand and Australia who have received the treatment so far 15 have an average of more than two years without needing transfusions and the rest less often, according to the results of two trials published today in the medical journal The New England Journal of Medicine. The adverse effects observed were not serious and are similar to those of other autologous transplants.
The drug is sold by the US company Bluebird Bio and is based on preclinical studies conducted by the teams of Philippe Leboulch, researcher at Brigham Women’s Hospital in Boston, and Marina Cavazzana, of the Paris-Descartes University. The treatment is already in the last phase of tests to measure its effectiveness in more than 30 patients in hospitals in the US and Europe. In addition, the evolution of patients already treated for 15 years will be followed.
These patients may be the first to be cured of this blood disease. “Once the genetic defect has been corrected and reinjected, the stem cells travel to their natural niches in the bone marrow” , explains José Carlos Segovia, researcher of the Innovative Therapies division in the Hematopoietic System of CIEMAT. “These cells remain active throughout life and produce healthy mature red blood cells, so with just one injection the ability to produce enough hemoglobin can be maintained for a long time. If the observed effects are sustained, we are in a situation very close to a cure of the disease ” , highlights.
The results are a new success for a type of therapy that has been in development for about three decades and that until recently had only achieved positive results. In 2016 Europe approved a gene therapy that corrects a mutation in a single gene in blood stem cells that causes deficiency of adenosine deaminase, a severe immunodeficiency encompassed within the so-called bubble-boy syndrome. Although for now applications have been limited to treating cells taken from patients and then reinjected, there are also ongoing trials in which another type of virus deactivated go to the liver to correct hemophilia. In Spain, five children have received gene therapy to correct fanconi anemia, explains Segovia, who hopes to launch another two similar trials for other rare diseases this year.
The company Crispr Therapeutics has received permission from the EU to start a clinical trial that uses a gene therapy combined with CRISPR against beta thalassemia, although they have not yet determined in which country the test will be performed, explains a company spokesperson Materia . In this case, the treatment modifies the BCL11A gene that produces hemoglobin during embryonic development and stops doing it after birth. The drug CTX001 of the company founded by Emmanuelle Charpentier, one of the creators of the new genetic editing technique, modifies that gene and allows it to re-synthesize the protein.