Comparativa entre les teràpies gèniques virals en desenvolupament contra la malaltia d’Alzheimer

Abstract

Alzheimer's disease has become one of the most common cause of dementia, especially among people over 65 years old, and its incidence is increasing worldwide. This neurodegenerative disease is characterized by the progressive loss of cognitive functions, significantly deteriorating patients' quality of life and posing a substantial burden on families and the healthcare system. The need to research effective treatments is urgent, as its impact is growing. The main causes of Alzheimer's are the accumulation of beta-amyloid peptide and the formation of hyperphosphorylated tau neurofibrillary tangles, genetic factors that cause chronic inflammation, microglia dysfunction and disruption of synaptic connections. Currently, the treatments focus on alleviating symptoms, using two major groups of medications: cholinergic and glutamatergic drugs. Cholinergic drugs increase acetylcholine levels, slowing the cognitive decline associated with Alzheimer's, while glutamatergic drugs act as antagonists of the NMDAR receptors, which play a crucial role in plasticity, neurotransmission and memory formation. At this time, the only treatment approved by the FDA in the United States to halt the progression of Alzheimer's is Lecanemab, a monoclonal antibody that aims to remove soluble beta-amyloid plaques from the brain. However, viral gene therapies are also being developed to combat the disease. The objective of this bibliographic work (with the bibliography consulted in scientific and specialized databases) is to analyse different research being conducted to develop viral gene therapies against Alzheimer's disease. It has been determined that most therapies aim to improve the immune system and combat the disease through autophagy, generally by modifying the chromosomal makeup of microglial cells to enhance their performance. The modifications include increasing BDNF expression, increasing progranulin expression, and changing the genome of APOE4 homozygotes to APOE2. In addition to autophagy techniques, there is a study which targets the reduction of tau expression. The treatments analysed in this work are in the early stages of development; some are in the preclinical phase, others in the discovery phase, and some are beginning the first clinical phases. In all of them, it has been determined that the most suitable vector for these therapies is the adeno-associated virus