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Novas abordagens terapêuticas para a doença de Alzheimer
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Abstract(s)
A doença de Alzheimer é uma das formas de demência mais comuns, representando cerca de 60 a 80% dos casos, tendo constituído a 7ª principal causa de morte em 2016, de acordo com a Organização para a Cooperação e Desenvolvimento Económico.
De facto, a par de um envelhecimento continuado da população, assiste-se a um aumento gradual da prevalência da doença de Alzheimer, assumindo atualmente o carácter de uma “epidemia” a nível mundial. Neste contexto, afigura-se importante o desenvolvimento de novos fármacos modificadores da doença, de modo a evitar que esta atinja estadios mais graves que afetem de forma determinante a vida social e as capacidades cognitivas do doente.
Esta doença caracteriza-se pela presença de marcadores patológicos específicos, nomeadamente, emaranhados neurofibrilares de proteína tau fosforilada e por placas senis compostas de proteína β amilóide, que conduzem à consequente neurodegeneração. A perda significativa e progressiva de neurónios está na base do desenvolvimento da doença cuja manifestação clínica se traduz no aparecimento dos primeiros sintomas, como a perda de memória e a incapacidade de realizar as atividades quotidianas.
Os últimos anos têm sido ricos no que concerne à realização de ensaios clínicos na área farmacoterapêutica da doença de Alzheimer, dos quais resultaram a aprovação de cinco fármacos para o tratamento sintomático da doença: quatro inibidores da acetilcolinesterase (tacrina, donezepilo, rivastigmina e galantamina) e, mais recentemente, um antagonista do recetor N-metil-D-aspartato (memantina). Porém, têm também existido resultados muito desanimadores, uma vez que muitos ensaios, na sua maioria de fase II/III, foram necessariamente interrompidos devido à ocorrência de efeitos adversos graves ou por falta de evidência de efetividade.
Neste contexto, é providencial a descoberta de novas moléculas, assim como de novos alvos terapêuticos que sejam efetivos para o tratamento da doença, mas para isso é necessário ter um maior conhecimento e compreensão da sua fisiopatologia.
Alzheimer’s disease is one of the most common forms of dementia, accounting about 60 to 80% of the cases, and it was the 7th leading cause of death in 2016 according to the Organization for Economic Cooperation and Development. In fact, alongside with the continued aging of the population, there is a gradual increase in the prevalence of Alzheimer’s disease, and is now becoming a worldwide “epidemia”. In this context, the development of new disease-modifying drugs is important in order to prevent the disease from reaching more severe stages that affect the social life and cognitive abilities of the patient. This disease is characterized by the presence of specific pathological markers, namely neurofibrillary tangles of phosphorylated tau protein and senile plaques composed of β amyloid protein, which lead to consequent neurodegeneration. The significant and progressive loss of cholinergic neurons underlies the development of the disease, whose clinical manifestation is the onset of early symptoms such as memory loss and inability to perform daily activities. Recent years have been rich in clinical trials in the pharmacotherapeutic field of Alzheimer’s disease, resulting in the approval of five drugs for symptomatic treatment of the disease: four acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine and galantamine) and, more recently, an N-methyl-D-aspartate receptor antagonist (memantine). However, there have also been very discouraging results, as many trials, mostly at phase II/III, have necessarily been discontinued due to serious adverse effects or lack of evidence of effectiveness. Thus, the discovery of new molecules, as well as new therapeutic targets that are effective for the treatment of the disease are still required, but it is also necessary to have a better knowledge and understanding of its pathophysiology.
Alzheimer’s disease is one of the most common forms of dementia, accounting about 60 to 80% of the cases, and it was the 7th leading cause of death in 2016 according to the Organization for Economic Cooperation and Development. In fact, alongside with the continued aging of the population, there is a gradual increase in the prevalence of Alzheimer’s disease, and is now becoming a worldwide “epidemia”. In this context, the development of new disease-modifying drugs is important in order to prevent the disease from reaching more severe stages that affect the social life and cognitive abilities of the patient. This disease is characterized by the presence of specific pathological markers, namely neurofibrillary tangles of phosphorylated tau protein and senile plaques composed of β amyloid protein, which lead to consequent neurodegeneration. The significant and progressive loss of cholinergic neurons underlies the development of the disease, whose clinical manifestation is the onset of early symptoms such as memory loss and inability to perform daily activities. Recent years have been rich in clinical trials in the pharmacotherapeutic field of Alzheimer’s disease, resulting in the approval of five drugs for symptomatic treatment of the disease: four acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine and galantamine) and, more recently, an N-methyl-D-aspartate receptor antagonist (memantine). However, there have also been very discouraging results, as many trials, mostly at phase II/III, have necessarily been discontinued due to serious adverse effects or lack of evidence of effectiveness. Thus, the discovery of new molecules, as well as new therapeutic targets that are effective for the treatment of the disease are still required, but it is also necessary to have a better knowledge and understanding of its pathophysiology.
Description
Keywords
Doença de Alzheimer Demência Proteína β Amilóide Proteína tau fosforilada Neurodegeneração Tratamento Novas terapêuticas Novas abordagens de tratamento para a doença de Alzheimer