Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy.

Rimeporide, a first-in-class sodium/proton exchanger Type 1 inhibitor (NHE-1 inhibitor) is repositioned by EspeRare for patients with Duchenne Muscular Dystrophy (DMD). Historically, NHE-1 inhibitors were developed for cardiac therapeutic interventions. There is considerable overlap in the pathophysiological mechanisms in Congestive Heart Failure (CHF) and in cardiomyopathy in DMD, therefore NHE-1 inhibition could be a promising pharmacological approach to the cardiac dysfunctions observed in DMD.

Not all imagery is created equal: A functional Magnetic resonance imaging study of internally driven and symbol driven musical performance imagery.

Playing a musical instrument requires fast multimodal sensory-motor processing which can be activated by voluntary access to performance imagery. Musicians use different methods to activate imagery for the purpose of "mental practice". The aim of the present study was to investigate cortical activation patterns in different methods of mental practice of musical performance.

The need for thorough phase II studies in medicines development for Alzheimer's disease.

An important factor in the universal failure in phase III trials in mild to moderate Alzheimer's disease in the past decade is the lack of phase II clinical data prior to entering phase III, with common reliance on biomarker results alone. Conduction of two learn-confirm cycles according to the Sheiner model would allow go/no-go decision making to include reliable clinical efficacy data prior to conducting phase III and would likely bring the rate of late stage failure more into line with that of other neurological indications. In studies in earlier disease stages, combined phase IIB/III adaptive approaches merit consideration in view of the long timelines of each study, though advantages and disadvantages of this approach versus the classical development pathway still need careful assessment.

Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.

Background: Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children.

Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study.

Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks.

Profiling the antibody immune response against blood stage malaria vaccine candidates.

Background: The complexity and diversity of the antibody immune response to the antigen repertoire of a pathogen has long been appreciated. Although it has been recognized that the detection of antibodies against multiple antigens dramatically improves the clinical sensitivity and specificity of diagnostic assays, the prognostic value of serum reactivity profiles against multiple microbial antigens in protection has not been investigated.

Methods: Using malaria as a model we investigated whether antigen reactivity profiles in serum of children with different levels of clinical immunity to Plasmodium falciparum malaria correlated with protection.

Allergen microarrays.

Allergy affects more than 25% of Western populations (1) and is estimated to be the sixth leading cause of chronic disease in the United States and Western Europe. The complexity of the condition is such that hundreds of common allergens have been described, and in order to maximize diagnostic efficiency there is an urgent clinical requirement for assays to provide multiple-allergen determination in a timely and cost-effective manner. Miniaturized immunoassays that utilize protein microarray technology now offer the possibility of circumventing most of the current limitations in the serodiagnosis of allergic disease.

Protein arrays for serodiagnosis of disease.

Protein microarrays offer the possibility to circumvent most of the current limitations in the serodiagnosis of allergy, autoimmune, and infectious disease by allowing the simultaneous, multiparametric determination of specific subclasses of antibodies directed against many pathogenic antigens. Microarray immunoassays have been developed with these characteristics. A first-generation assay, for the serodiagnosis of infectious disease, allows the determination of IgG and IgM antibodies to various viral and bacterial antigens.

Protein microarray technology for unraveling the antibody specificity repertoire against microbial proteomes.

The genomes of microorganisms responsible for diseases of worldwide medical importance have been sequenced or will be available in the near future. Combinatorial cloning technologies for producing large numbers of proteins have been developed and high-throughput assays such as protein microarrays have been clinically validated for detecting the presence of antibodies directed against microbial antigens in human serum. These scientific and technical achievements offer the opportunity to investigate the natural immune response against the whole proteome of a variety of microorganisms.