Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure

Nonconventional MRI and microstructural cerebral changes in multiple sclerosis

MRI has become the most important paraclinical tool for diagnosing and monitoring patients with multiple sclerosis (MS). However, conventional MRI sequences are largely nonspecific in the pathology they reveal, and only provide a limited view of the complex morphological changes associated with MS. Nonconventional MRI techniques, such as magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) promise to complement existing techniques by revealing more-specific information on microstructural tissue changes. Past years have witnessed dramatic advances in the acquisition and analysis of such imaging data, and numerous studies have used these tools to probe tissue alterations associated with MS. Other MRI-based techniques-such as myelin-water imaging, 23 Na imaging, magnetic resonance elastography and magnetic resonance perfusion imaging-might also shed new light on disease-associated changes. This Review summarizes the rapid technical progress in the use of MRI in patients with MS, with a focus on nonconventional structural MRI. We critically discuss the present utility of nonconventional MRI in MS, and provide an outlook on future applications, including clinical practice. This information should allow appropriate selection of advanced MRI techniques, and facilitate their use in future studies of this disease

Regenerating CNS myelin — from mechanisms to experimental medicines

Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination