Alzheimer’s disease is
one of the leading neurological disorders across the world. Therelevanceof treating Alzheimer’s disease with masitinib was confirmed by the studies
conducted by Francois Piette et al. The study was
sponsored by AB Sciences, Paris, a pharmaceutical company specializing in the
research, development and commercialization of protein kinase inhibitors (PKIs).
An important point in the pathogenesis of Alzheimer’s disease is
neuroinflammation. Mast cells are
involved in the inflammation processes and influence the permeability of blood
brain barrier. Masitinib is a selective
inhibitor of tyrosine kinase and effectively inhibits the survival and activity
of mast cells.
A placebo- controlled randomized
phase 2 study was carried out in patients with mild to moderate Alzheimer’s
disease. In these patients,
masitinib was
administered as an adjunct to cholinesterase inhibitor and/ or memantine.
The study included assigning
masitinib with
starting dose of 3 or 6 mg/kg/day or placebo randomly. The regime was given
twice daily for 24 weeks. Alteration from the baseline in the Alzheimer’s
disease Assessment Scale-cognitive subscale (ADAS-Cog) was taken as the primary
endpoint.
After 12 and 24 weeks the rate of clinical
cognitive lowering as per ADAS-Cog response was found to be lower with
adjunctive treatment with masitinib in contrast to placebo (6% versus 50% for
both time points). Significant
improvements were noted with mastinib treatment on ADAS-Cog, ADCS-ADL (Alzheimer's
Disease Cooperative Study - Activities of Daily Living), and Mini-Mental State Examination (MMSE), whereas the placebo
treatment resulted in relative deterioration of the same.
The side-
effects seen were mild to moderate in intensity and transient, more pronounced
with masitinib treatment (65% versus 38% of patients). Strong adverse effects
were observed almost at same occurrence rate with masitinib and placebo
administration (15% versus 13% of patients, respectively). Gastrointestinal
disorders, edema and rashes were the commonly seen mastinib- related side
effects.
The studies concluded that masitinib add- on
administration for 24 weeks resulted in improvement of Alzheimer’s disease. The use of masitinib provided a pioneering
opportunity for curing Alzheimer Disease.
References:
1. Piette F et al. Masitinib as an Adjunct Therapy for
Alzheimer's Disease published in Alzheimer's Research & Therapy 2011, 3: 16.
Source-Medindia