Practical Considerations for Building Priors for Confirmatory Studies
Mani Lakshminarayanan, Fanni Natanegara in Bayesian Applications in Pharmaceutical Development, 2019
Being able to borrow information from previous studies is an appealing and exciting feature of Bayesian methods. However, use of historical information in confirmatory trials always poses a challenge because verification of the underlying assumption of exchangeability is difficult. This chapter will discuss considerations of integrating historical information into confirmatory trials from a practical perspective, using the development of treatment for spinal muscular atrophy as an example. Section 3.1 will introduce the clinical program and different data sources available at the planning stage and the possible impact of such data sources on designing the phase III trials. Section 3.2 will review the corresponding statistical models that are applicable for analyzing the historical and the phase III data together through Bayesian borrowing techniques. Section 3.3 will present the analyses results and the operation characteristics of some selected simulation scenarios, and a discussion of further thoughts will be in Section 3.4 .
Chronic Denervation Myopathy
Maher Kurdi in Neuromuscular Pathology Made Easy, 2021
Long-standing neurogenic disease may result in denervation of the target musculature. This is rare in clinical practice and usually referred to as chronic denervation myopathy. The spectrum of potential causes ranges from hereditary or sporadic genetic mutations to several acquired causes. Aging of muscle and some metabolic conditions are also accompanied by neuropathy. The most common sporadic or hereditary cause is anterior horn cell degeneration of the central nervous system due to amyotrophic lateral sclerosis in adulthood or spinal muscular atrophy in childhood. Secondary acquired causes include any disease present with severe peripheral neuropathy, due to any cause, affecting the innervated muscle. In this chapter, we describe the histopathological findings of cases with chronic denervation atrophy and also discuss the clinical phenotypes of spinal muscular atrophy.
Introduction
Z. Yang in Finite Element Analysis for Biomedical Engineering Applications, 2019
Chapter 1 presents the outline of the book. The main topics include bone, covered in Chapters 2 through 5; soft tissues, from Chapters 6 through 11; joints, from Chapters 12 through 14; and implants, from Chapters 15 through 18. The final chapter, Chapter 19, is retrospective, summarizing some guidelines for simulation of the biomedical problems given in the book. Each topic starts by describing the structure and function of the biology and then follows the relevant finite element advanced features, such as anisotropic nonlinear material, fiber enhancement, multidimensional interpolation, UserHyper, porous media, contact wear simulation, the eXtended Finite Element Method (XFEM), and crack growth fatigue analysis. The final section models some specific biomedical problems, such as abdominal aortic aneurysm (AAA), intervertebral discs (IVDs), head impact, knee contact, spinal muscular atrophy (SMA) cardiovascular stent, hip replacement, and mini dental implants. All modeling files are attached in the appendixes of the book.
Spinal Muscular Atrophy and Common Therapeutic Advances
Published in Fetal and Pediatric Pathology, 2019
Saeed Bozorg Qomi, Amir Asghari, Arash Salmaninejad, Majid Mojarrad
Background: Spinal muscular atrophy (SMA) is an autosomal recessive destructive motor neuron disease which is characterized primarily by the degeneration of α-motor neurons in the ventral gray horn of the spinal cord. It mainly affects children and represents the most common reason of inherited infant mortality. Material and Methods: We provide an overview of the recent therapeutic strategies for the treatment of SMA together with available and developing therapeutic strategies. For this purpose, Google Scholar and PubMed databases were searched for literature on SMA, therapy and treatment. Titles were reviewed and 96 were selected and assessed in this paper. Result: Over the last two decades, different therapeutic strategies have been proposed for SMA. Some methods are in the pre-clinical, others the clinical phase. Conclusion: By emergence of the new approaches, especially in gene therapy, effective treatment in the close future is probable.
How far away is spinal muscular atrophy gene therapy?
Published in Expert Review of Neurotherapeutics, 2015
Thomas H Gillingwater, Lyndsay M Murray
Spinal muscular atrophy (SMA) is a devastating motor neuron disease primarily affecting children, for which there is currently no known disease-modifying therapy or cure. The identification of the disease gene, survival motor neuron, led to an expansion in SMA research and allowed the creation of numerous animal and cellular models. This led to a significant increase in our understanding of the pathophysiology of SMA, culminating in the development of multiple SMN-dependent and -independent therapies. Among the most exciting options, viral gene therapy has emerged as one leading candidate. A growing body of pre-clinical evidence suggests that administration of scAAV9 carrying an SMN transgene can be both efficacious and translationally viable. In this article, we briefly review the progress which has been made in the field, and provide a commentary on some of the challenges which remain.
Advances and challenges in developing a therapy for spinal muscular atrophy
Published in Expert Review of Neurotherapeutics, 2015
Ryan S Anderton, Frank L Mastaglia
Spinal muscular atrophy (SMA) is a debilitating and incurable childhood onset disease characterized by the degeneration of motor neurons in the spinal cord resulting in muscular atrophy and paralysis. Over the past 20 years, there has been significant progress in understanding the molecular basis of the disease, allowing researchers to identify the main causative gene and successfully model SMA in various animals. Despite an improved understanding of the disease, there is still no effective treatment for SMA patients. Here, we discuss the current knowledge surrounding the pathogenesis of SMA, and outline recent advances toward the development of a successful therapy for this devastating disease.
Related Knowledge Centers
- Motor Neuron Disease
- Progressive Bulbar Palsy
- Spinal Cord Diseases
- Spinal Cord
- II
- Spinal Muscular Atrophies of Childhood
- Recessive