The drug administered for “compassionate use” to little Alberto, 16 months old, who arrived at the Buzzi Children’s Hospital in Milan with a respiratory infection
Alberto, the name is fictional, was 16 months old when in the summer of 2021 he was admitted to the Vittore Buzzi Children’s Hospital in Milan. He has a respiratory infection and the doctors try to figure out the cause. After a long series of investigations, specialists finally arrive at the diagnosis: Acid Sphingomyelinase Deficiency (ASMD), a rare lysosomal disease known as Niemann Pick’s Disease (A, B or mixed AB). It is a disease that can be very serious, even fatal within the first 10 years, but for which today there is an experimental cure that can greatly improve the life expectancy of the children who suffer from it. However, therapy must begin early, before the patient’s condition becomes complicated and instead, as often happens with rare diseases, it often happens that the diagnosis is late.
800 thousand rare patients in Italy
It is estimated that around 300 million people, of which 800 thousand in Italy, are affected by over 6 thousand rare diseases, surveyed by the World Health Organization (WHO). Namely as the third largest nation in the world. For the most part, over 70%, are pathologies of genetic origin, often chronic and fatal, which manifest themselves already in childhood. “Rare diseases affect a small number of people and consequently cause specific problems linked to their rarity – underlines Gian Vincenzo Zuccotti, dean of the Faculty of Medicine of the State University of Milan and director of Pediatrics and Pediatric Emergency Department of Asst Fatebenefratelli- Sacco, Vittore Buzzi Children’s Hospital -. Having an infrequent disease entails greater difficulties from the beginning: longer times (sometimes even several years) to arrive at a correct diagnosis, to reach doctors and specialized centers and, almost always, to have an effective therapy. When there is. Unfortunately, acid sphingomyelinase is often recognized late (between 3 and 5 years of age), when it has already caused various damages and the situation has become complicated ».
Because it is essential to start a treatment immediately
Therefore, in his misfortune (the acid sphingomyelinase deficiency affects 0.3-0.6 children per 100 thousand births) Alberto had at least partly a good luck: to give his disease a name immediately and to be able to start therapy promptly. “To date, there is no treatment available for ASMD – explains Zuccotti -, but there is a compassionate use program, that is, the free supply of a drug (Olipudase alfa), which is still undergoing a phase III clinical trial (the last before a medicine receives final marketing approval), but which is proving to be safe and effective ‘. Starting a treatment for children suffering from acid sphingomyelinase deficiency is decisive because in this pathology, following a genetic defect, a sufficient amount of the specific enzyme is not produced which normally has the task of degrading a substance called sphingomyelin, present in the whole body is necessary for cellular functions. When this enzymatic activity is deficient, sphingomyelin accumulates progressively in the cells, damaging them, with a spectrum of symptoms that depend on the affected organs and with a significant reduction in life expectancy.
Symptoms not to be overlooked
“Typically sphingomyelin accumulates in the liver and spleen with an increase in volume and impaired organ function – explains Laura Fiori, head of the Buzzi Congenital Metabolic Diseases group and pediatrician treating the little patient together with Chiara Montanari -. In technical terms, this increase in volume causes hepatomegaly and splenomegaly, which can be evident from the first months of life in the earliest onset forms, associated with difficulty in eating, anemia and piastinopenia. Another important symptom is difficulty in breathing, due to interstitial pulmonary infiltrate from accumulation of sphingomyelin: the young patients have frequent respiratory infections and recurrent dyspnea “. Just like in the case of Alberto, who currently has a significant increase in the volume of liver and spleen and moderate pulmonary involvement, growth retardation and skeletal maturation are also frequent in these children. Death, usually in the first decade of life, can occur from respiratory or hepatic insufficiency. In the type A form, severe neurological degeneration is also present with delayed acquisition of the developmental and regression stages from the first months of life. “These patients often do not survive beyond three years of age – warns Fiori -. The pediatrician must therefore suspect this lysosomal pathology (in differential diagnosis with other lysosomal diseases such as Gaucher’s disease) in particular in the case of hepatosplenomegaly, recurrent respiratory difficulty, poor growth, anemia or low platelet count with no other known cause, with onset during early childhood, with or without neurological problems “.
What does “compassionate use” mean
Fortunately Alberto does not yet have a neurological involvement. Fundamental for the prognosis is to stop the accumulation of sphingomyelin and eliminate the one already accumulated in the organs, to restore their functions and guarantee the child survival with a good quality of life. Treatment with Olipudase alfa represents enzyme replacement therapy, that is the recombinant form (produced by genetically modified cells) of the physiological enzyme that the child is lacking. “The compassionate use program by the manufacturing company (Sanofi) allows patients to receive this treatment already today, which is still being studied and not approved in Italy, but which, according to the data available so far, seems capable to halt the progression of the disease, thus improving life expectancy and reducing organ complications “underlines the expert. ) for the treatment of patients with serious illnesses, rare diseases, rare cancers or in conditions of life threatening disease, for whom valid therapeutic alternatives are not available or who cannot be included in a clinical trial or, for the purposes of therapeutic continuity, for patients already treated with clinical benefit in the context of a concluded clinical trial. The supply is free of charge by the pharmaceutical company.
A hope for Alberto
The request is made by a doctor for nominal use (ie for a single patient), who submits it to the evaluation of the hospital ethics committee, after having received the OK from the manufacturer. “Alberto is currently the second child in Italy who was given the opportunity to receive this therapy: on 10 January 2022 he received his first dose of Olipudase alfa at the Metabolic Diseases day hospital of the Buzzi Hospital, without adverse reactions – concludes Zuccotti -. He is continuing therapy and follow up with an enzyme infusion every two weeks (second dose administered on 24/2) and will perform periodic clinical and metabolic checks, in order to evaluate his clinical picture and the effect of the drug. According to the results of the clinical studies carried out so far on other patients, thanks to the therapy with Olipudase alfa we also expect in Alberto an improvement in hepatosplenomegaly, a decrease in respiratory infections and a regular growth, thanks also to the diagnosis made early before the the establishment of serious organ damage “.
January 27, 2022 (change January 27, 2022 | 10:58)
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