Promoting myelin repair is one of the most promising therapeutic avenues in the field of myelin disorders. In future clinical trials, evaluation of remyelination will require a reliable and quantifiable myelin marker to be used as a surrogate marker. To date, MRI assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2-methoxy benzene (BMB), a synthesized fluorescent molecule, that binds selectively to myelin both ex vivo and in vivo. The binding of BMB to myelin allows the detection of demyelinating lesions in an experimental autoimmune encephalitis model of demyelination and allows a mean for quantifying myelin loss in dysmyelinating mutants. In multiple sclerosis brain, different levels of BMB binding differentiated remyelination in shadow plaques from either demyelinated lesions or normal-appearing white matter. After systemic injection, BMB crosses the blood-brain barrier and binds to myelin in a dose-dependent and reversible manner. Finally, we provide evidence that 11 C-radiolabeled BMB can be used in vivo to image CNS myelin by positron-emission tomography in baboon. Our results provide a perspective for developing a brain myelin imaging technique by positron-emission tomography.multiple sclerosis ͉ remyelination ͉ leukodystrophy M yelin is a unique structure in the nervous system that allows rapid, economic, and secure conduction of impulses along axons. The loss or lack of myelin resulting from an acquired or inherited disease may produce a delay or failure of conduction in affected fibers, with concomitant neurological dysfunction. In the human CNS, multiple sclerosis (MS) is the most common acquired demyelinating disease, affecting Ϸ2 million people worldwide (1). The leukodystrophies, induced by inherited enzyme deficiencies, also affect CNS white matter, resulting in abnormal formation, destruction, or turnover of myelin sheaths (2). Both acquired and inherited myelin disorders share a poor prognosis, leading to major disability in young people.Spontaneous remyelination can occur in the CNS and was first demonstrated by electron microscopy of lesions in the adult mammalian spinal cord (3). Remyelination results in the formation of short and thin myelinated internodes, but it enables the restoration of a sufficient conduction along axons and allows some functional recovery (4, 5). In demyelinating diseases such as MS, this regenerative process does occur and sometimes proceeds to completion (6), but it is less efficient than in experimental animal models (7). Improving repair processes can theoretically be achieved by either promoting endogenous repair mechanisms or providing an exogenous source of myelinating cells by transplantation (8-10). Clinical trials are expected to be carried out in the latter field soon.A major clinical issue of such trials is to assess and quantify myelin repair in vivo. To date, MRI is the reference test for diagnosing and monitoring the evolution of white-matter diseases (2, 11, 12). Unfortunatel...

No abstract

No abstract

Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance-guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

No abstract