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New advances in treatment of Alzheimer's disease: passive immunotherapy and stem cell therapies
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A população idosa tem aumentado gradualmente nas últimas décadas, acompanhada por um crescimento no número de doenças relacionadas com a idade avançada – em especial, doenças neurodegenerativas. A doença de Alzheimer (AD) é considerada o tipo de demência mais devastador, com cerca de 55 milhões de pessoas diagnosticadas com esta doença em 2020. Estima- se que este número continue a aumentar durante os próximos anos.
A AD é responsável por disfunções cognitivas marcantes, nomeadamente a perda de memória e dificuldades linguísticas e de raciocínio, resultando em perda de independência e por fim na morte. As opções terapêuticas atualmente disponíveis (donepezilo, rivastigmina, galantamina e memantina) oferecem, no máximo, um alívio temporário de sintomas, sem efeitos reais na prevenção da progressão da doença. Por este motivo, o desenvolvimento de novas estratégias direcionadas aos mecanismos patológicos subjacentes à doença de Alzheimer mostra- se como uma necessidade urgente. Duas terapias inovadoras foram exploradas em detalhe em estudos pré-clínicos e clínicos: Imunoterapia passiva e terapia com células estaminais. Considerando estratégias de imunização passiva, foram selecionados e revistos os anticorpos monoclonais Aducanumab, Lecanemab e Donanemab, relativamente à sua eficácia na remoção de placas β-amiloide do cérebro de pacientes com AD.
Na abordagem com células estaminais, foram analisados mecanismos de reparação neuronal após a administração de fatores de crescimento e de agentes que promovem a neurogénese endógena – Sovateltide, Allopregnanolone e GV1001. Os efeitos dos agentes Neurostem, Lomecel-B, Fração vascular estromal derivada do tecido adiposo (ADSVF) e vesículas extracelulares foram explorados para o tratamento com células estaminais exógenas.
Para além da eficácia, aspetos como a segurança, potenciais riscos, limitações, pontos de melhoria e estado de aprovação por parte das agências reguladoras foram analisados para as abordagens terapêuticas descritas. Embora ainda em etapas iniciais de desenvolvimento, com vários desafios e questões a ser clarificadas, estes novos agentes terapêuticos representam um futuro promissor no tratamento da doença de Alzheimer.
The elderly population has been gradually increasing for the past decades, accompanied by a growing number of diseases related to old age - in particular, neurodegenerative diseases. Alzheimer’s Disease (AD) is considered the most devastating form of dementia, with around 55 million people living with this disease in 2020. This number is expected to continuously increase over the next years. AD is responsible for remarkable cognitive dysfunctions, such as memory loss, thinking and linguistic difficulties, resulting in loss of independence and ultimately death. Therapeutic options currently available (donepezil, rivastigmine, galantamine and memantine) offer, at most, a temporary symptom relief, with no real effects on stopping disease progression. For this reason, the development of new strategies to address the underlying pathological mechanisms of AD comes as an urgent need. Two innovative therapies were explored in detail in preclinical and clinical studies: Passive immunotherapy and stem cell therapies. For passive immunization strategies, the monoclonal antibodies Aducanumab, Lecanemab and Donanemab were selected and revised regarding their efficacy on removing amyloid plaques from the brain of AD patients. As for the stem cell approach, neuronal repairing mechanisms were analyzed following the administration of growth factors and agents that promote endogenous neurogenesis - such as Sovateltide, Allopregnanolone and GV1001. The effects of Neurostem, Lomecel-B, Adipose - derived stromal vascular fraction (ADSVF) and Extracellular Vesicles were explained as an exogenous stem cell treatment. Besides efficacy, aspects such as safety, potential risks, limitations, improvement points and approval status by regulatory agencies were analyzed for the described therapeutic approaches. While still in early development stages, with several challenges and questions to be answered, these new therapeutic agents represent a promising future on Alzheimer’s disease treatment.
The elderly population has been gradually increasing for the past decades, accompanied by a growing number of diseases related to old age - in particular, neurodegenerative diseases. Alzheimer’s Disease (AD) is considered the most devastating form of dementia, with around 55 million people living with this disease in 2020. This number is expected to continuously increase over the next years. AD is responsible for remarkable cognitive dysfunctions, such as memory loss, thinking and linguistic difficulties, resulting in loss of independence and ultimately death. Therapeutic options currently available (donepezil, rivastigmine, galantamine and memantine) offer, at most, a temporary symptom relief, with no real effects on stopping disease progression. For this reason, the development of new strategies to address the underlying pathological mechanisms of AD comes as an urgent need. Two innovative therapies were explored in detail in preclinical and clinical studies: Passive immunotherapy and stem cell therapies. For passive immunization strategies, the monoclonal antibodies Aducanumab, Lecanemab and Donanemab were selected and revised regarding their efficacy on removing amyloid plaques from the brain of AD patients. As for the stem cell approach, neuronal repairing mechanisms were analyzed following the administration of growth factors and agents that promote endogenous neurogenesis - such as Sovateltide, Allopregnanolone and GV1001. The effects of Neurostem, Lomecel-B, Adipose - derived stromal vascular fraction (ADSVF) and Extracellular Vesicles were explained as an exogenous stem cell treatment. Besides efficacy, aspects such as safety, potential risks, limitations, improvement points and approval status by regulatory agencies were analyzed for the described therapeutic approaches. While still in early development stages, with several challenges and questions to be answered, these new therapeutic agents represent a promising future on Alzheimer’s disease treatment.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Alzheimer’s disease β-amyloid Monoclonal antibodies Neuroregeneration Stem cells Mestrado Integrado - 2024