View clinical trials related to Muscular Atrophy, Spinal.
Filter by:This is an observational multicenter retrospective and prospective study on natural history of SMA also considering the 'new natural history' secondary to the availability of commercially available therapies. All the patients enrolled to date in the Italian registry, if not part of clinical trials, will be included in the present study.
The first cure for Spinal Muscular Atrophy (SMA; Nusinersen) has been approved by FDA in 2017. Although it improves the clinical picture of most SMA patients, not all exhibit the same response to treatment. In this project the aim will be: i. identifying cell-free SMN circular RNAs (circRNAs) in body fluids of SMA patients as potential biomarkers before and after Nusinersen; ii. evaluating their prognostic power as predictors of the clinical response of SMA patients to Nusinersen; iii. identifying human intronic polymorphisms that affect SMN circRNAs biogenesis and impact on the efficacy of Nusinersen. The results obtainable with this project will evaluate if different concentration of cell free SMN circRNAs in SMA patients could underlie the genotype-phenotype mismatch, usually observed, and the reduced response of a subset of SMA patients to therapy. Our research could highlight the need for these of combinatorial 'SMN-plus' and "personalized" therapies that account for individual differences.
Spinal Muscular Atrophy (SMA) is a life-threatening disease in infancy that is caused by inactivating mutations in the Survival Motor Neuron 1 (SMN1) gene1,2. SMN1 mutations lead to deficiency in SMN protein, which results in degeneration of motor neurons in the spinal cord, progressive muscle weakness and atrophy. The almost identical SMN2 gene does not suffice SMN function, because skipping of exon 7 in its mRNA yields an unstable protein. Nevertheless, SMN2 represents a disease modifier gene and increasing its expression or rescuing its splicing defect have long been considered elective strategies for SMA1,2. After substantial translational research efforts, the first therapies eliciting clinical benefits for SMA patients have recently become available3. Nusinersen, an antisense oligonucleotide (ASO), and Risdiplasm, a small molecule, bind the SMN2 RNA and promote splicing of exon 7. On the other hand, Zolgesma, an adeno-associated virus delivering the SMN1 gene (scAAV9-SMN), bypasses the need to correct the splicing defect. Nevertheless, none of these therapies currently represents a complete cure for patients, because not all of them respond equally and in a significant portion of patients the symptoms are attenuated but not corrected3. It is believed that early treatment, possibly at a pre-symptomatic stage, would positively affect the clinical response and may significantly improve patient's management. However, another critical point is the current lack of information on the long-term efficacy and safety of the current treatments4. In this scenario, it is likely that further elucidation of the biological functions of the SMN genes and the identification of robust biomarkers for stratification of patients will set the ground for more "personalized" therapies, which may account for the clinical variability observed in patients and help improving the therapies in use.
This is an investigator initiated observational study with the aim to record several aspects of function, care and adverse events in a large cohort of SMA patients followed longitudinally by using a structured academic disease registry.
The goal of this multicenter, open-label, non-comparative, cohort study is to investigate the safety, immunogenicity, and efficacy of ANB-004 in children with spinal muscular atrophy. The study will have a standard 3+3 dose-escalation design.
SMA (Spinal Muscular Atrophy) is a rare neuromuscular disease characterized by motoneuron damage. Symptoms consist of respiratory involvement with numerous respiratory infections and eventually respiratory failure, for which NIV (Non Invasive Ventilation) is often used. Ventilation machines are in close contact with the respiratory tract of patients. They contain heated water to humidify the circuit. These humid and warm environments are conducive to the development of bacteria such as Pseudomonas aeruginosa. In this context, it is interesting to look for the presence or absence of bacteria, in comparison with the respiratory ecology of the patients. The aim is to highlight the microbiological role of NIV on the occurrence of respiratory bacterial infections or secondary infections in patients with SMA. To do this, samples are taken from the machines, and ECBCs are performed on patients during respiratory physiotherapy sessions.
Motor neuron disease (MND) or ALS is a nervous system disease. ALS leads to a loss of movement ability that eventually leads to death. At the moment, there is no known treatment for ALS. Early diagnosis in individuals improves clinical care and facilitates timely entry into clinical trials. However, current methods for diagnosis are primarily clinical, and to date, no cost-effective biomarkers have been developed. Our objective is to identify a robust non-invasive neurophysiological-based system that can be used both as a biomarker of disease onset, and a measurement of progression using quantitative EEG and surface EMG (bipolar and high-density). The investigators postulate that analysing the joint recordings of EEG and EMG (bipolar or high-density) can give measures that better distinguish healthy people and ALS patient subgroups and that the findings can be developed as biomarkers of early diagnosis and disease progression.
Spinal muscular atrophy (SMA) is a genetic disease of the nervous system that affects about 1 in 7,0001.2 births and results in very high mortality for patients with the disease. There are about 120 new cases in France each year and an estimated total of 2500 patients. It is the leading cause of genetic mortality in children in France. Until 2017, no etiological treatment was available. Currently, three treatments have been approved and have authorizations in France. The current clinical developments in SMA show the importance of an early treatment for patients. 3. The identification of pre-symptomatic patients is therefore essential to improve the effectiveness of treatments on an individual level and to avoid any loss of chance, as well as to reduce the societal cost of disability for patients treated in post-symptomatic. Several countries in Europe and around the world have implemented regional pilot screening programs for the disease. The screening test is based on a molecular genetic analysis that has been performed for many years, and which is highly reliable; there is currently no biochemical marker that can be used. The objective of our project is to demonstrate the feasibility of neonatal screening for spinal amyotrophy in two French regions before being able to propose to extend it to the whole of France. The management of all screened patients will be decided outside the pilot study, by the existing national multidisciplinary consultation meeting, according to the best available standards of care and will be based on the national network of neuromuscular disease reference centers The objective of the project is not the evaluation of the efficacy of treatments or neonatal screening: these objectives are being studied by existing or otherwise ongoing studies around the world. This project has been set up to be in line with the existing structures in France that are responsible for neonatal screening (via the regional neonatal screening centers (CRDN) and the regional perinatal networks) and for the management of rare diseases (via the neuromuscular disease reference centers and their FILNEMUS network). This project is performed in collaboration with AFM Telethon, Directorate of Health Care Supply, Regional Health Agency (ARS), FILNEMUS network, Novartis Gene Therapies, Roche Pharma AG,Biogen. Investigator wish, as far as possible, to bring this study closer to real life and to be able to generate as much information as possible that can be used directly to prefigure the potential generalization of this screening strategy to the entire national territory.
An outpatient rehabilitation program for children (6 months to less than 6 years old) with Spinal Muscular Atrophy (SMA) treated with genetic based therapies is being studied. Participants will participate in a 12-week therapy program where they receive 45 minutes each of occupational therapy and physical therapy each week. Home exercises will also be prescribed to be completed 5 days per week. At the end of the therapy program, there will be a 12-week period of no therapy where only home exercises will be completed. Assessments and program evaluation will occur at the beginning (Week 0) and end of the rehabilitation program (Week 24), then at the end of the no therapy block (week 24).
The primary objective of the study is to describe the natural history and utilization of disease modifying therapy (DMT) among adult Chinese participants with SMA linked to chromosome 5q (5q-SMA).