Gene therapy potentially cures sickle cell anemia and transfusion-dependent thalassemia

At the national meeting of the conclusions of the 65th annual congress of the American Association of Hematology (ASH), organized by the Spanish Society of Hematology and Hemotherapy (SEHH) and held at the Zaragoza Conference Center, they were presented and analyzed the main advances in the field of hematology and hematology. specialty “Hematology and Hemotherapy” in relation to both malignant hematological diseases (or blood cancer) and non-malignant hematological diseases (coagulopathies such as hemophilia or others, thrombosis, anemia, erythrocyte pathologies, spinal insufficiency, etc.).

It is in the field of erythropathology (the field that deals with the treatment of red blood cell disorders) that very important advances have been made in the treatment of sickle cell disease and transfusion-dependent thalassemia, two genetic diseases of hemoglobin. “The first of them is characterized by acute episodes of very severe pain that appear unexpectedly, in addition to other acute complications, anemia and chronic damage to all organs. Secondly, in order to survive, these patients need monthly blood transfusions, which leads to iron overload and, as a result, potential damage to many organs,” explains Salvador Payan, hematologist at the Virgen del Rocío University Hospital in Seville. . .

“Devastating Treatment and Potential Cure”

“The advent of gene therapy to treat these diseases represents a disruptive treatment and potential cure,” says the specialist. In fact, the “pearl of erythropathology” at the last congress ASH was gene therapy, as the results of using the drugs exa-cel and lovo-cel for the treatment of sickle cell anemia were presented. These results indicate that the primary goal of the study was achieved, as the majority of patients were pain-free at twelve months.

During the last congress ASHBoth treatments have been approved by the US Food and Drug Administration for the treatment of sickle cell disease.FDA according to the English abbreviation). Likewise, “results from exa-cel in transfusion-dependent thalassemia were presented, demonstrating that all patients receiving this therapy achieve transfusion independence,” says Dr. Payan.

Hemophilia is another hematological bleeding disorder for which gene therapy has been proposed as a possible treatment. “IN ESH 2023 The good results from the HOPE-B trial were announced to continue, in which more than 87% of hemophilia B patients treated with etranacogene dezaparvovec achieved normalization of hemostasis or mild disease,” explains Ms. Teresa Alvarez. Roman, hematologist at the La Paz University Hospital in Madrid. “In addition,” he adds, “new gene therapy strategies for hemophilia with CRISPR/Cas technology, optimized transgenes and RNA silencers were presented in San Diego.”

Advances in thrombocytopenia and anticoagulation

On the other hand, as stated by Luisa Lozano, a hematologist at the Morales Meseguer University Hospital in Murcia, “promising results from preclinical models are presented on the possible benefit of CAR-T therapy in immune thrombocytopenia or ITP.” , opening up wide possibilities for the use of this type of treatment.

Dr. Lozano also noted the emergence of a new entity of interest to hematologists, which was described in 2023 under the name VITT-like (similar to vaccine-induced thrombotic thrombocytopenia). “We should suspect these conditions in individuals with a history, especially of respiratory infections that cause thrombosis, thrombocytopenia of 20,000 to 80,000 platelets, and elevated D-dimer levels. In these cases, and because of the high mortality rate associated with this new disease, we must ask the patient to administer platelet factor IV antibodies and urgently begin anticoagulant treatment and intravenous immunoglobulins.

In the field of anticoagulation, important developments were also presented in ESH 2023. In particular, the results of numerous ongoing studies of a new generation of anticoagulants, factor XI inhibitors, were presented. “Until now, after antivitamin K drugs, direct oral anticoagulants (DOACs) have represented great progress in this field. In fact, although they have been around for several years, many specialists continue to call them new anticoagulants,” explains Cristina Sierra, hematologist at the Cruces University Hospital in Baracaldo, Vizcaya. “However, the emergence of this new therapeutic target will revolutionize the world of anticoagulants, especially in complex patients, the elderly, those with kidney failure or at risk of bleeding,” he concluded.