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Abstract(s)
A esclerose lateral amiotrófica é uma doença neurológica progressivamente fatal que afeta
os neurónios motores superiores e inferiores, dando origem a fraqueza, atrofia muscular e
levando à morte, cerca de dois a cinco anos após o início dos sintomas. Na base da sua
etiologia estão fatores genéticos e ambientais, mas os mecanismos patofisiológicos
associados à doença, como o aumento do stress oxidativo, a excitotoxicidade e a disfunção
da homeostase proteica, que levam à acumulação de agregados de proteínas nos neurónios,
estão longe de serem completamente entendidos. O tratamento centra-se em cuidados de
suporte, e em apenas duas opções farmacológicas disponíveis, o riluzole e o edavarone,
que oferecem efeitos modestos e limitados. As células estaminais surgem como uma
abordagem terapêutica promissora, dado a sua capacidade de diferenciação em diferentes
linhagens celulares neuronais e não neuronais e o potencial de neuroproteção através da
secreção de fatores tróficos, melhorando o ambiente circundante dos tecidos lesados,
tendo já demonstrado segurança e eficácia em inúmeros ensaios clínicos. Apesar dos
avanços científicos neste campo, alguns desafios persistem, como a seleção dos pacientes
nestes ensaios, a janela terapêutica ideal e a otimização das doses terapêuticas. Apesar do
potencial terapêutico, obstáculos como a tumorogénese e a diferenciação não controlada
requerem uma avaliação rigorosa. O desenvolvimento de protocolos padronizados de
investigação e tratamento é urgente, para atingir a consistência e a reprodutibilidade
desejada, para que esta abordagem terapêutica possa revolucionar a gestão dos pacientes
de uma doença devastadora como a esclerose lateral amiotrófica.
Amyotrophic lateral sclerosis is a progressively fatal neurological disease that affects both upper and lower motor neurons, resulting in weakness, muscle atrophy, and leading to death approximately two to five years after symptom onset. The etiology of ALS involves genetic and environmental factors, but the pathophysiological mechanisms associated with the disease, such as increased oxidative stress, excitotoxicity, and protein homeostasis dysfunction leading to the accumulation of protein aggregates in neurons, are far from completely understood. Treatment focuses on supportive care, with only two available pharmacological options, riluzole and edaravone, providing modest and limited effects. Stem cells emerge as a promising therapeutic approach due to their ability to differentiate into various neuronal and non-neuronal cell lineages and their potential for neuroprotection through the secretion of trophic factors, improving the surrounding environment of damaged tissues. They have already demonstrated safety and efficacy in numerous clinical trials. Despite scientific advancements in this field, challenges persist, including patient selection in these trials, the optimal therapeutic window, and the optimization of therapeutic doses, among others. Despite therapeutic potential, obstacles such as tumorigenesis and uncontrolled differentiation require rigorous evaluation. The development of standardized research and treatment protocols is urgent to achieve the desired consistency and reproducibility, allowing this therapeutic approach to revolutionize the management of patients with a devastating disease like amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis is a progressively fatal neurological disease that affects both upper and lower motor neurons, resulting in weakness, muscle atrophy, and leading to death approximately two to five years after symptom onset. The etiology of ALS involves genetic and environmental factors, but the pathophysiological mechanisms associated with the disease, such as increased oxidative stress, excitotoxicity, and protein homeostasis dysfunction leading to the accumulation of protein aggregates in neurons, are far from completely understood. Treatment focuses on supportive care, with only two available pharmacological options, riluzole and edaravone, providing modest and limited effects. Stem cells emerge as a promising therapeutic approach due to their ability to differentiate into various neuronal and non-neuronal cell lineages and their potential for neuroprotection through the secretion of trophic factors, improving the surrounding environment of damaged tissues. They have already demonstrated safety and efficacy in numerous clinical trials. Despite scientific advancements in this field, challenges persist, including patient selection in these trials, the optimal therapeutic window, and the optimization of therapeutic doses, among others. Despite therapeutic potential, obstacles such as tumorigenesis and uncontrolled differentiation require rigorous evaluation. The development of standardized research and treatment protocols is urgent to achieve the desired consistency and reproducibility, allowing this therapeutic approach to revolutionize the management of patients with a devastating disease like amyotrophic lateral sclerosis.
Description
Keywords
Células
Estaminais Células Estaminais Mesenquimais Células Estaminais Neuronais Células Estaminais Pluripotentes Induzidas Ela Esclerose Lateral Amiotrófica Mecanismos Patofisiológicos Tratamento