ABSTRACT
Abstract Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.
Resumen La enfermedad de Alzheimer (EA) es la forma más frecuente de demencia de inicio en el adulto, caracterizada por un deterioro progresivo en la cognición y la memoria. No hay cura para la enfermedad y los tratamientos actuales son sólo sintomáticos. El descubrimiento de fármacos es un proceso costoso y que consume mucho tiempo; en la última década no se han encontrado nuevos fármacos para la EA a pesar de los esfuerzos de la comunidad científica y las compañías farmacéuticas. La inmunoterapia contra Aβ es uno de los enfoques más prometedores para modificar el curso de la EA. Esta estrategia terapéutica utiliza péptidos sintéticos o anticuerpos monoclonales (mAb) para disminuir la carga de Aβ en el cerebro y retardar la progresión de la enfermedad. Por lo tanto, este artículo discutirá los principales aspectos de la neuropatogénesis de la EA, el tratamiento farmacológico clásico, así como la inmunización activa y pasiva describiendo los prototipos de fármacos evaluados en diferentes ensayos clínicos.
Subject(s)
Humans , Amyloid beta-Peptides/immunology , Alzheimer Disease/therapy , Immunotherapy/methods , Peptides/therapeutic use , Peptides/pharmacology , Disease Progression , Alzheimer Disease/physiopathology , Alzheimer Disease/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/pharmacologyABSTRACT
In 1906 Alois Alzheimer, described the cerebral lesions characteristic of the disorder that received his name: senile plaques and neurofibrillary tangles. Alzheimer's disease (AD) is now, 100 years after, the most prevalent form of dementia in the world. The longer life expectancy and aging of the population renders it as a serious public health problem of the future. Urgent methods of diagnosis and treatment are required, since the definitive diagnosis of AD continues to be neuropathologic. In the last 30 years several drugs have been approved to retard the progression of the disease; however, there are still no curative or preventive treatments. Although still in experimentation, the visualization of amyloid deposition by positron emission tomography or magnetic resonance imaging will allow in vivo diagnosis of AD. In addition, experiments with the amyloid vaccine are still ongoing, and very recent data suggest that intravenous gammaglobulins may be beneficial and safe for the treatment of AD.