To cure, first of all you need to know. Thus, the arrival of innovative therapies can only be truly revolutionary if they can reach the patients who could benefit most from them. And the revolution in the field of therapies against SMA, spinal muscular atrophy, has happened in recent years and how. “We have three different types of drugs available which, although not completely decisive, allow us to treat children affected by the disease already in the very first months of life, and to change their life and that of the whole family”, says Anita Pallara , President of FamiglieSMA. “Today children with SMA are able to stay seated, can eat, breathe independently: these are achievements that fill us with life. It’s a whole different SMA ”. But starting a clinical path can only start from a diagnosis, which first arrives, the first allows patients and their families to earn a living. This is why today more than ever the appeal of clinicians and the association is for the extension of newborn screening. Now that the first gene therapy has arrived in the armamentarium against the disease.
SMA is the first gene therapy
SMA is a degenerative genetic disease that affects motor neurons, the neurons that operate muscles, due to mutations in the SMN1 gene (Survival Motor Neuron 1). There are different forms, depending on the severity and copy number of another gene, SMN2, which produces a similar but shorter protein than that produced by SMN1. “Gene therapy against SMA is indicated for the most severe form of the disease, where, in the absence of treatment, less than 10% of children reach the age of two”, explained Eugenio Mercuri, Director of the Child Neuropsychiatry Complex Operating Unit, Gemelli Polyclinic, Rome Agostino Gemelli University Polyclinic Foundation IRCCS. “SMA1 also affects the muscles, as a consequence of the failure of motor neurons, not only the skeletal ones, but also the respiratory and swallowing ones. This is why children not only cannot sit up but also have problems with swallowing and respiratory functions ”. Gene therapy, alongside the other available options, provides concrete possibilities for both improvements in function and in the life expectancy of patients, continues Mercuri: “We used to talk and see a disease with a terrible progression, today these children can manage to to walk. But it is good to be cautious, remember that we have no certainties and above all that the expectations are different if the drug is administered at different times: we are talking about treatments that work well, yes, but a lot depends on when they are given “.
Gene therapy aims to restore the function of the SMN gene by introducing the DNA (packaged inside an adenoviral vector) in a single dose administered intravenously. Today in Italy it is available for clinically diagnosed type 1 SMA patients and weighing up to 13.5 kg, and for pre-symptomatic patients (and who have up to 2 copies of the SMN2 gene).
Aifa approves the first gene therapy against SMA
The importance of time
“It is our duty as much to convey the enthusiasm for the arrival of new therapies, as well as to dose expectations for different situations, which depend on the therapies but also on any respiratory, nutritional assistance and physiotherapy therapies that may be necessary”, he also reiterates Valeria Sansone, director of the Clinic of the NeMO Center in Milan, Associate Professor of Neurology at the University of Milan, “In general, we know that the sooner we start a treatment, the better”. Because the difference, Mercuri resumes, is not only the what but also when this something is administered. “We know there are excellent effects in the populations of children included in clinical trials, and we are working to see if it can be safely extended to heavier children,” continues Mercuri. The reference is to the SMART study which will investigate the safety and efficacy of therapy in children with SMA and weighing between 8.5 kg and 21 kg.
Let’s “Play Advance” against SMA to change the history of the disease
The results in still asymptomatic children
The data already in the possession of clinicians, however, reaffirm the importance of early treatment, such as those presented at the Muscular Dystrophy Association Virtual Clinical and Scientific Conference, which involved children with pre-symptomatic SMA undergoing gene therapy: “We are talking about amazing results : children with pre-symptomatic SMA have the possibility of acquiring developmental milestones comparable to those of children without the disease, that is, we could have an appropriate development for their age if we were able to identify all eligible patients early ”.
Rare diseases: Luca’s journey
by Irma D’Aria
It is precisely these results that underline, once again, the importance of early diagnosis that passes from newborn screening. For now in Italy we are talking only of pilot programs launched thanks to private funds, as happened for Lazio, Tuscany, and now also Piedmont and Liguria, as explained by Francesco Danilo Tiziano, of the Institute of Medicine at the Catholic University of the Sacred Heart: “With our pilot project in Tuscany and Lazio we tested about 74 thousand children, identifying 14 in just over a year and a half, but neither of the two regions has a regional regulation that identifies the path that will take place after the end of the project. pilot, as it has already been established in Puglia ”. Screening, the experts repeat, has value where there are effective therapies, and Sma today is one of them: “With newborn screening we can reach a diagnosis within 9 days, compared to two months for severe forms of the disease. ”, Tiziano goes on:“ Diagnostic delays risk becoming lost possibilities ”. The hope is that something will change soon: by the end of May, in fact, other pathologies should be discussed to be included in newborn screening.
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