For years there Franco and Piera Cutino Onlus Foundation is alongside patients with thalassemia, in order to significantly improve the quality of their life. One of the most pursued objectives is to raise awareness among the population about prevention methods, present opportunities to combat the pathology and therapies being tested. For this reason, World Thalassemia Day will be accompanied, throughout the month of May, by some precious ones initiatives.
Thalassemia: the initiatives of May 2024
Among the initiatives proposed by Franco and Piera Cutino Onlus Foundation there are the talk onlineconducted by Sergio Mangano, communication Manager. In scheduled meetings every Friday of the month at 6pm on the Foundation’s social channelswe talk about scientific research and innovative therapies, we start a dialogue with clinicians and patients from various reference centers, we address common fears, we ask ourselves how the quality of life of patients can be improved.
In addition to online talks, the11 maggio the Foundation will be present atExpo Comics & Games (pavilion 21 of the Mediterranean Fair, Palermo) with an information stand. Thanks to a partnership, the comic school of the Sicilian capital will donate the proceeds from the sale of drawings and illustrations to the Foundation.
Il 16 maggio instead, it will be the turn of the great chefs’ dinner “By starlight” organized by Mag, Master Academy Antonino Galvagno. The evening, which will be held at the Giardini del Massimo, will feature great names in cuisine and pastry making. Part of the proceeds from the dinner will be used to purchase two health tablets for the “Cutino” Hematology Campus. To close the calendar, a fundraising dinner organized by the Foundation on May 25th at the San Paolo Palace Hotel in Palermo.
What is thalassemia?
L’hemoglobin it is a molecule contained in red blood cells that transports oxygen to all the tissues, organs and muscles of the body. It is made up of two proteins:alpha globulin and the beta globulin. When one of these two has “defective” genes, an anomaly occurs, which causes the destruction of red blood cells and favors the emergence of achronic anemia. In the presence of these conditions we speak of thalassemiawhose name comes from the union of the two Greek words “thàlassa” (sea) and “haîma” (blood), to underline its diffusion especially in the areas overlooking the Mediterranean Sea.
Why are there more thalassemia patients in some areas of Italy than others?
If the genetic defect affects alpha globulin then it is called alpha thalassemia, more frequent in North Africa and the Middle East. If the genetic error is caused by the beta globulin, we have the beta thalassemia (or Mediterranean anemia), more common in Greece, Turkish coastal regions, islands such as Malta and Corsica, and Italy.
«In our country there are approximately 7000 thalassemia patientsdistributed mainly among Sicily, Sardinia, Po Delta, Liguria and some southern regions» explains Mangano. «The presence of the disease in certain geographical areas is explained by the fact that these have always historically been marshy areas infested with malaria. In thalassemia patients, the genetic anomaly hinders the reproduction of the parasitic microorganism that causes malaria, automatically making patients more resistant to this infectious disease. This has led, over the years, to favoring the settlement of people with thalassemia in certain Italian regions” continues the doctor.
How is it transmitted?
The only way to get thalassemia is inherit one or more defective genes from your parents. «In the case of beta thalassemia, which as we have seen is the most widespread form in our peninsula, there are only two genes involved. You get one from the mother and one from the father” confirms Mangano. «If only one of the two genes is affected by the error, the unborn child will develop a talassemia minor, generally asymptomatic, and therefore will be a healthy carrier of the pathology. If both genes are defective then the baby will suffer talassemia major (or Cooley’s disease), which is the most serious and disabling form.”
What does it mean to be a healthy carrier of thalassemia?
Who is a healthy carrier is in good health, so much so that he often doesn’t know he’s affected by it. However, marrying a partner who is also a healthy carrier could result in a 25% chance of passing on both defective genes and giving birth to a child with thalassemia major. In 50% of cases, however, the unborn child could inherit just one damaged gene and, in turn, be a healthy carrier of the disease. Finally, in the remaining 25% of cases the child may not inherit any defective genes and therefore be completely healthy. Fortunately, a couple looking for a child can, nowadays, find out in advance whether they are healthy carriers by undergoing a specific blood test.
With coelocentesis it is possible to know if the unborn child will have thalassemia
Healthy carrier couples can then learn about the health of the fetus through some prenatal diagnostic tests. In addition to the traditional techniques of villocentesis e amniocentesisa third option has been added for a few years, less invasive but equally effective: the coelocentesis.
«Following a study conducted by the “Vincenzo Cervello” Hospital of Palermo and supported entirely by the Piera Cutino Onlus Association, this test was developed which allows for transvaginal sampling, between the seventh and ninth week, of small amount of coelomic fluid to understand whether the fetus is affected by thalassemia or not” explains Mangano. Currently the Sicilian structure is the only one in Europe to offer this procedure, which is provided by the National Health Service and has 100% diagnostic reliability.
How does thalassemia manifest itself?
The most serious form of thalassemia, the major one, presents with symptoms already around 5-6 months of life. «In these subjects the red blood cells are pale and deformed so much so that the spleen, recognizing their defective appearance, destroys them early. By doing so, however, the blood has few red blood cells and a form of chronic anemia develops, which results in exhaustion, pale complexion, lack of appetite, low-grade fever e yellowing of the skin and eyes» continues the representative of the Foundation.
«Moreover, every red blood cell destroyed releases a small amount of iron into the blood which in the long run is deposited in the pancreas, liver and heart, causing progressive damage to these organs. The spleen becomes abnormally enlarged and bone marrow activity causes problems with the osteo-articular system».
Blood transfusions and iron chelation therapy
However, thanks to the evolution of therapies, the history of the pathology has undergone a significant transformation over the years. «Until thirty years ago, patients almost never lived beyond 20-25 years of life, which was spent with a thousand difficulties. Today, however, a child with thalassemia has an open prognosis, that is can live long and in good healthcan study, work and have children” confirms Mangano.
What over time has clearly contributed to improving the quality of life of thalassemia patients and increasing their survival are certainly the transfusions, which are done every 15-20 days. The goal is to get new red blood cells into the blood to prevent anemia and all other disorders.
«Even with transfusions, however, the problem ofiron accumulation, released into the bloodstream by each eliminated red blood cell. To prevent it from depositing in different organs, the patient can follow, in association with transfusions, a therapy with iron chelating drugs. There are various molecules that are able to bind excess iron and eliminate it, in order to keep its levels in the blood below the toxicity threshold” confirms the expert.
Bone marrow transplant
There are also other therapeutic solutions. The first is represented by bone marrow transplant. «This procedure consists of replacement of thalassemia stem cells with those taken from the bone marrow of a compatible donor. After being transfused into the patient, the stem cells begin to produce new red blood cells which gradually replace the defective ones. Unfortunately, this therapy is conditioned not only by the availability of a compatible donor but also from a series of risks, such as the body’s rejection of transplanted cells. Therefore, it is usually preferable to opt for blood transfusions and iron chelation therapies” explains Dr. Mangano.
Gene therapy
Finally, the other therapeutic approach is represented by gene therapy. «It is a procedure that consists of collection of stem cells from the patient’s marrow. These are then taken to the laboratory and modified by inserting a healthy gene, which replaces the defective one. These cells are then reintroduced into the bone marrow of the thalassemia patient, where they gradually take root and begin to produce healthy red blood cells” concludes Sergio Mangano.
In February 2024 the European Commission granted conditional marketing authorization for exagamglogene autotemcel (exa-cel), a genome editing therapy based on CRISPR/Cas9 technology. The drug is approved for the treatment of patients aged 12 years and older with transfusion-dependent beta thalassemia. This therapy involves the genetic modification of hematopoietic stem cells taken from the patient himself. Once reinfused, these cells allow the production of high levels of fetal hemoglobin (HbF) in red blood cells, counteracting the main consequences of transfusion-dependent beta thalassemia.