Treatment of patients with spinal muscular atrophy in Croatia - positive results from the national registry and new challenges

Abstract

Spinal muscular atrophy is an autosomal recessive, progressive degenerative disease caused by mutation of the SMN1 (survival of motor neuron 1) gene on chromosome 5q. Eff ective patient care and success of standardized therapeutic approaches taken to achieve better quality of life require multidisciplinary therapeutic approach and coordination of a large number of specialists. Successful outcome of diagnostic and therapeutic procedures is based on the application of the standardized procedure. It begins with early recognition of clinical signs and symptoms, as well as the risk of complications. Early application of non-invasive ventilation and cough assist device together with orthopaedic approach to scoliosis signifi cantly alter the natural course of the disease. Antisense oligonucleotide (AON) nusinersen and small molecules are directed to enhancing inclusion of exon 7 in SMN2 mRNK and formation of a stable and functional protein, and gene therapy (onasemnogene abeparvovec) is an example of SMN1 gene replacement therapy. Results of treatment with nusinersen show improvement on motor function scales, which is most pronounced in the fi rst 6 to 12 months of therapy in spinal muscular atrophy type I, with good tolerability and safety. Earlier application of modifying therapy for spinal muscular atrophy, primarily for type I, may signifi cantly change of the natural course and outcomes of the disease in terms of halting disease progression, as well as establishing progress in motor development. There are currently no strict internationally accepted criteria for inclusion of diff erent genetic or gene therapies in patients according to disease type or duration, patient age and dependence on permanent mechanical invasive ventilation. Additional studies are required to evaluate therapeutic effi cacy, therapeutic window, duration of treatment, drug dose, side eff ects related to long-term use and treatment outcome, preferably eff ects on ventilation and swallowing, eff ect on cognitive development, scoliosis, growth and autonomic function, and objectivity of the rating scale for motor functions. In conclusion, early genetic diagnosis, neonatal screening and application of target therapy that modifi es the course of the disease, timely monitoring and treatment of respiratory, cardiologic and gastroenterological complications, as well as early onset of the transition period are crucial parts of the care for spinal muscular atrophy patients. In order to improve patient care, it is important to enable treatment possibilities according to standards of care, ongoing evaluation of the criteria for inclusion and termination of modifying therapy, relieving centres for tertiary level of care, reducing the number of disease related hospitalizations and individual access to each patient, along with encouraging the establishment of patient registries for neuromuscular disorders at the national level, as well as in diff erent countries around the world, and their interconnection and cooperation.