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Authors
Abstract(s)
A doença de Alzheimer (DA) é a causa mais comum de demência. Caracteriza-se
por défice mnésico precoce seguido de deterioração progressiva dos restantes domínios
cognitivos.
Esta tese almeja rever literatura sobre terapias anti-amilóides, mais
especificamente imunoterapia passiva e os novos desenvolvimentos acerca dos
anticorpos monoclonais bem como a sua eficácia e segurança.
A pesquisa foi realizada com recurso às bases de dados “Pubmed”, “Cochrane
Library” e “MEDLINE”.
O tratamento atual da DA é meramente sintomático e não há tratamento
modificador de prognóstico.
A hipótese amilóide defende que a DA depende da deposição de beta-amiloide no
tecido cerebral. Tendo esta teoria como base, foram criadas em 1999 as primeiras vacinas
contra beta-amilóide. No entanto, os seus efeitos adversos proeminentes levaram à
investigação da imunização passiva como uma alternativa mais segura. A aprovação
rápida do primeiro anticorpo monoclonal para o tratamento da DA (aducanumab)
levantou algumas suspeitas acerca da sua eficácia e segurança. Na verdade, há uma falta
de evidência quanto à eficácia de vários anticorpos monoclonais alternativos nos seus
ensaios clínicos.
Apesar das expectativas altas no que concerne ao aducanumab, não há evidência
suficiente, quanto à sua eficácia clínica, que apoie o seu uso na prática médica. Além
disso, este tratamento apresenta indicações restritas e efeitos adversos potencialmente
danosos. De facto, outros anticorpos monoclonais não demonstraram benefício cognitivo
em ensaios clínicos apesar de se verificar uma diminuição da deposição de placas
amilóides in vitro, facto que sugere uma fisiopatologia multifatorial da DA.
Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by early memory deficit followed by progressive deterioration of the remaining cognitive domains. This thesis aims to review literature about anti-amyloid therapies, more specifically passive immunotherapy and the new developments about monoclonal antibodies and their efficacy and safety The research took place in the main databases such as Pubmed, Cochrane Library and MEDLINE. The current AD treatment is merely symptomatic and currently there is no proven prognostic modifier treatment. The amyloid hypothesis states that AD depends on the deposition of betaamyloid in the brain tissue. Based on this theory, the first vaccines against betaamyloid were created in 1999, however its prominent side effects turned the research towards passive immunization as a safer alternative. The recent fast-track approval, of the first monoclonal antibody for the treatment of AD (aducanumab) has raised some eyebrows regarding its efficacy and safety. Many other monoclonal antibodies still lack proof of their efficacy in their clinical trials. Despite the high expectations surrounding aducanumab, there was not enough substantiated evidence about its effect on cognitive decline to uphold its use in clinical practice. Farther, this therapy has restricted indications and potentially serious side effects. Although other monoclonal antibodies show a decreased deposition of amyloid plaques in vitro, they failed to show improvement in clinical trials, which suggests a multifactorial pathophysiology of AD.
Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by early memory deficit followed by progressive deterioration of the remaining cognitive domains. This thesis aims to review literature about anti-amyloid therapies, more specifically passive immunotherapy and the new developments about monoclonal antibodies and their efficacy and safety The research took place in the main databases such as Pubmed, Cochrane Library and MEDLINE. The current AD treatment is merely symptomatic and currently there is no proven prognostic modifier treatment. The amyloid hypothesis states that AD depends on the deposition of betaamyloid in the brain tissue. Based on this theory, the first vaccines against betaamyloid were created in 1999, however its prominent side effects turned the research towards passive immunization as a safer alternative. The recent fast-track approval, of the first monoclonal antibody for the treatment of AD (aducanumab) has raised some eyebrows regarding its efficacy and safety. Many other monoclonal antibodies still lack proof of their efficacy in their clinical trials. Despite the high expectations surrounding aducanumab, there was not enough substantiated evidence about its effect on cognitive decline to uphold its use in clinical practice. Farther, this therapy has restricted indications and potentially serious side effects. Although other monoclonal antibodies show a decreased deposition of amyloid plaques in vitro, they failed to show improvement in clinical trials, which suggests a multifactorial pathophysiology of AD.
Description
Keywords
Anti-Amilóide Anticorpos Monoclonais Beta Amiloide Doença de Alzheimer Tratamento Alzheimer