Categorization of the amyotrophic lateral sclerosis population via the clinical determinant of post-onset ΔFS for study design and medical practice.

The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS-R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS-R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS-R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management.

Masitinib for mild-to-moderate Alzheimer's disease: results from a randomized, placebo-controlled, phase 3, clinical trial.

Background: Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer's disease (AD).

Methods: Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial.

Efficacy and Safety of Masitinib in Corticosteroid-Dependent Severe Asthma: A Randomized Placebo-Controlled Trial.

Background: Masitinib is an oral tyrosine kinase inhibitor that selectively targets mast cell activity and platelet-derived growth factor receptor (PDGFR) signaling, both of which are implicated in various mechanisms of asthma pathogenesis.

Objective: Assessment of masitinib as an add-on to standard maintenance therapy as compared with placebo in the treatment of oral corticosteroid-dependent severe asthma.

Methods: We conducted a randomized (2:1), placebo-controlled study of masitinib (6 mg/kg/d) in adults with severe asthma uncontrolled by high dose inhaled corticosteroids and long-acting beta-adrenoreceptor agonists plus oral corticosteroids (OCS) (≥7.

Long-term survival analysis of masitinib in amyotrophic lateral sclerosis.

Background: A randomized, placebo-controlled phase III study (AB10015) previously demonstrated that orally administered masitinib (4.5 mg/kg/day) slowed rate of functional decline, with acceptable safety, in amyotrophic lateral sclerosis (ALS) patients having an ALS Functional Rating Scale-revised (ALSFRS-R) progression rate from disease onset to baseline of <1.1 points/month.

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial.

To assess masitinib in the treatment of ALS. Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.

Glass microstructure capping and bonding techniques.

The capping of microfluidic features fabricated in glass substrates is achievable by various technological methods. Of the entire spectrum of possibilities (gluing, glass bonding via intermediate layers, pressure or plasma-assisted glass bonding, etc.) a detailed description of three techniques is presented here.

Introduction to glass microstructuring techniques.

In this chapter an overview of manufacturing methods, leading to the fabrication of microstructures in glass substrates, is presented. Glass is a material of excellent optical properties, a very good electric insulator, biocompatible and chemically stable. In addition to its intrinsic qualities, glass can be processed with the use of manufacturing methods originating from the microelectronic industry.

Mast cell leukemia: identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine kinase inhibitor.

Objective: Most patients with systemic mastocytosis bear mutations in the tyrosine kinase receptor gene c-Kit. Limited treatment options exist for mast cell leukemia, a rare form of systemic mastocytosis associated with a dire prognosis. Our aim was to investigate c-Kit mutations associated with mast cell leukemia and find new treatment for this severe form of mastocytosis.

Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study.

Treatment options for patients suffering from indolent forms of mastocytosis remain inadequate with the hyperactivation of mast cells responsible for many of the disease's systemic manifestations. Masitinib is a potent and highly selective oral tyrosine kinase inhibitor. A combined inhibition of c-Kit and Lyn make it particularly efficient in controlling the activity of mast cells and therefore, of potential therapeutic benefit in mastocytosis.

Masitinib combined with standard gemcitabine chemotherapy: in vitro and in vivo studies in human pancreatic tumour cell lines and ectopic mouse model.

Background: Tyrosine kinases are attractive targets for pancreatic cancer therapy because several are over-expressed, including PDGFRalpha/beta, FAK, Src and Lyn. A critical role of mast cells in the development of pancreatic cancer has also been reported. Masitinib is a tyrosine kinase inhibitor that selectively targets c-Kit, PDGFRalpha/beta, Lyn, and to a lesser extent the FAK pathway, without inhibiting kinases of known toxicities.

Grafting of antibodies inside integrated microfluidic-microoptic devices by means of automated microcontact printing.

A novel approach to integrating biochip and microfluidic devices is reported in which microcontact printing is a key fabrication technique. The process is performed using an automated microcontact printer that has been developed as an application-specific tool. As proof-of-concept the instrument is used to consecutively and selectively graft patterns of antibodies at the bottom of a glass channel for use in microfluidic immunoassays.

Masitinib for the treatment of canine atopic dermatitis: a pilot study.

There is an on-going need to identify medications suitable for the long-term treatment of canine atopic dermatitis (CAD). Masitinib mesilate is a potent and selective tyrosine kinase inhibitor of the c-KIT receptor. A strong relationship exists between the SCF/c-KIT pathway and pathogenesis of CAD, suggesting that masitinib may potentially fulfil the above role.

Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT.

Background: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT.

Methodology/principal Findings: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC(50)) of 200+/-40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC(50) of 150+/-80 nM in Ba/F3 cells expressing human or mouse wild-type KIT.

Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study.

Introduction: Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA.

Methods: This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial.

A new instrument for automated microcontact printing with stamp load adjustment.

An instrument for automated microcontact printing (microCP) on microscope slides is described. The movement of the stamp, which is actuated by a computer controlled pneumatic actuator, is precisely guided until it makes contact with the substrate. As a consequence, the absolute position of the microprinted patterns is reproducible over a series of substrates with 1 mum standard deviation.

Evaluation of static thermal and near-infrared hyperspectral imaging for the diagnosis of acute maxillary rhinosinusitis.

Although acute maxillary rhinosinusitis may be confidently diagnosed based on a history and physical examination by trained specialists, its diagnosis by primary health workers is less dependable, with a tendency for overdiagnosis, often resulting in inappropriate treatment. It is commonly perceived among the otolaryngology community that a new and objective diagnostic tool would be beneficial, facilitating the widespread and reliable diagnosis of rhinosinusitis. Numerous merits of thermal imaging make it an attractive modality to fulfill this role.

Laminar fluid diffusion interface preconditioning of serum and urine for reagent-free infrared clinical analysis and diagnostics.

A number of reagent-free infrared spectroscopic diagnostic and analytical methods have been established previously making use of dry biofluid films. For example, this approach has successfully measured high concentration analytes of serum and urine. However, a number of low concentration diagnostically relevant analytes presently elude detection by infrared spectroscopy.