View clinical trials related to Atrophy.
Filter by:The purpose of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of NMD670 in the treatment of ambulatory adults with spinal muscular atrophy type 3
The primary objectives of the study are to prospectively evaluate pregnancy complications and outcomes in participants with SMA, birth outcomes and adverse effects in infants born to participants with SMA, who were exposed to nusinersen up to 14 months prior to the first day of their last menstrual period (LMP) before conception, 14.5 months before the date of conception, and/or at any time during their pregnancy. The secondary objective of the study is to evaluate pregnancy outcomes in participants with SMA exposed to nusinersen as compared with participants without SMA who were not exposed to nusinersen (e.g., participants from external, general population comparators).
Major breakthroughs in the treatment for Spinal muscular atrophy (SMA) have been recently achieved with various therapeutic approaches that increase full-length SMN protein levels. The variability observed following the advent of commercial availability of Nusinersen for all types of SMA has highlighted the need to identify tools that may allow to predict possible therapeutic responses. The aim of this project is to establish whether an integrated approach using clinical, imaging (muscle MRI) and circulating biomarkers, can provide the possibility to develop a predictive model of therapeutic response to novel therapies for SMA patients. More specifically we wish to establish the correlation between clinical response, different biomarkers indicative of central nervous system efficacy (e.g. determination of neurofilaments levels), and markers that provide evidence of the skeletal muscle response (e.g. serum myostatin and muscle imaging) in different types of SMA
Spinal Muscular Atrophy (SMA) is caused by the homozygous loss of the Survival Motor Neuron (SMN) 1 gene, which leads to degeneration of spinal alpha-motor neurons and muscle atrophy. Three treatments have been approved for SMA but the available data show interpatient variability in therapy response and, to date, individual factors such as age or SMN2 copies,cannot fully explain this variance. The aim of this project is: - collect clinical data and patient-reported outcome measures (PROM) from patients treated with nusinersen, risdiplam, onasemnogene abeparvovec, - identify novel biomarkers and RNA molecular signature profiling, - develop a predictive algorithm using artificial intelligence (AI) methodologies based on machine learning (ML), able to integrate clinical outcomes, patients' characteristics, and specific biomarkers. This effort will help to better stratify the SMA patients and to predict their therapeutic outcome, thus to address patients towards personalized therapies.
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.
A Randomized, Double-blind, Placebo-controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of AOC 1020 Administered Intravenously to Adult Participants with Facioscapulohumeral Muscular Dystrophy (FSHD)
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.
10 patients having deficient anterior maxilla will be recruited and a preoperative CBCT will be done to evaluate the vertical and horizontal dimensions of the intended alveolar ridge. pre-operative manufacturing of the digital surgical guides performed for Harvesting of the chin cortical bone struts from the symphysial area in the donor site and for Placement of the grafted cortical bone struts and the implant in the recipient site. Intra operatively the donor site (Chin) will be prepared to harvest autogenous bone from the chin aided by the patient's prefabricated bone harvesting guide. The recipient site (Maxillary anterior defect) will be prepared to receive the chin grafts. Grafts will be screwed in position and implants will be screwed in its preparation until it gains primary stability from basal bone, using the prefabricated bone fixation-implant placement guide. Any gaps will be filled with autogenous bone particulates from the chin. A healing tie base Abutment will be screwed into the implant through the third cortex. Primary stability will be assessed using Osstell device. An immediate postoperative CBCT will be done and superimposed on the preoperative CBCT to measure accuracy of plan transfer to make sure the planning was followed accurately. Follow up after 6 months and CBCT will be done for bone formation and density assessment and implant exposure for implant stability measurement-using osstell and removal Healing abutment and consecutive prosthetic loading.