Background. Onasemnogene abeparvovec is the first gene replacement therapy medication based on the adeno-associated viral vector (AAV9). One injection to a patient with 5q spinal muscular atrophy (SMA) leads to replacement of the missing or defective SMN1 gene with its functional copy. It leads to normalization of survival motor neuron protein (SMN) production. Objective. The aim of the study is to evaluate efficacy, safety, and causes of different responses to therapy after single administration of onasemnogene abeparvovec in 5 patients with 5q SMA (types I and II) comparing the baseline status with the results of continued monitoring in real clinical practice in Russian Federation. Methods. Interim results of continued follow-up of children with 5q SMA with 2–3 copies of the SMN2 gene are presented: 2 boys and 1 girl with type I who received single dose of onasemnogene abeparvovec at 4 and 7 months of age; and 2 girls with type II who received therapy at 11 and 16 months of age. Results. Short-term controlled fever was observed in 4 out of 5 patients during first 2 weeks after viral vector therapy administration (max in patient 5 — up to 38.5 ° C). All 5 children had transaminases increase, 1 patient — significant transaminases increase during the sensitisation period (> 10 from upper normal level (UNL)), 1 patient — delayed significant transaminases increase (> 20 UNL), 1 patient — transaminases increase (> 3 UNL) after discontinuation of longterm therapy with glucocorticosteroids (according to prescribing information). All patients had shown positive and sustained response to therapy over time at motor status assessment via CHOP INTEND / HFMSE scales. The more significant response was observed in patients with less aggressive baseline 5q SMA type II with 3 copies of the SMN2 gene. Conclusion. Onasemnogene abeparvovec is relatively safe medication for management of children with 5q SMA. Thus, the development of adverse events and their mechanisms should be further studied, as well as long-term follow-up of recipients is required to gather knowledge on this medication effects on human body.
В статье рассматривается история развития земельного налогообложения, начиная с Древних времён по настоящее время, рассматривается значимость земельного налога в формировании местного бюджета. По результатам проведенного исследования можно смело говорить о том, что земельное налогообложение занимает особое место в налоговой системе Российской Федерации. На примере МО Городского округа «город Улан-Удэ» было выявлено, что земельный налог занимает сравнительно невысокую долю в местном бюджете, однако земельный налог выступает в качестве важного источника формирования бюджета поселения. В современной России земельный налог рассматривается как эффективный механизм управления земельными ресурсами. Ключевые слова: земельный налог, история земельного налогообложения, бюджеты муниципальных образований, управление земельными ресурсами.
Background. Dystrophic myotonia type 1 (DM1) is the most common muscular dystrophy in patients of any age. Myotonia “delayed relaxation of muscle” is the leading symptom in DM1 and can occur at any time after onset disease. Myotonia symptoms and electrical myotonia registration are delayed after onset in patients with congenital and infantile forms of DM1. This makes it difficult to diagnose and prevent fatal complications in these patients in a timely manner. Objective: presentation of the clinical data and results of needle electromyography in patients with DM1 onset in the first decade of the life; determination of the first symptoms of the disease, to estimate the age of myotonia and electrical myotonia manifestation for the optimization of the timely diagnostics of the disease.Materials and methods. 13 patients with DM1 aged from 2 months to 34 years were described. 10 patients underwent needle electromyography with analysis of spontaneous activity and needle EMG pattern. The diagnosis was made on the basis of clinical and paraclinical manifestations of the disease and identification of an increase in CTG repeats (>50) in the DMPK gene.Results. The onset with extramuscular signs of respiratory and/or feeding disturbances, dysarthria, school learning disorders, autism spectrum disturbance and “floppy infant syndrome” was noted as the first symptoms of the disease. Clinical myotonia symptoms and electrical manifestations of myotonia were absent in all patients for a long time after the disease onset. DM1 was confirmed in all mothers, however in 5 cases the onset of the disease was later than the first symptoms in patients with congenital and childhood onset forms of DM1.Conclusion. The first symptoms of the congenital and infantile forms of DM1 are not specific and occur in a wide range of diseases. Such discriminating signs of DM1 as clinical myotonia, distal muscle atrophy and electrical myotonia appear much later than the onset disease. In the group of patients before and after the formation of phrasal speech, the presented combinations of symptoms allow diagnostics of the congenital and infantile forms of DM1 at the onset of the disease. In its turn, it allows genetic counseling in burdened families and timely prevention of fatal complications.
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