CLINICAL TRIALS AND TREATMENT UPDATES FOR AMYOTROPHIC LATERAL SCLEROSIS (ELA) BETWEEN 2020 AND 2025

• DOI: https://doi.org/10.22533/at.ed.1595102511026

• Palavras-chave: Amyotrophic Lateral Sclerosis; Edaravone; Riluzole; Clinical Trials;

• Keywords: Amyotrophic Lateral Sclerosis; Edaravone; Riluzole; Clinical Trials;

• Abstract:

  Amyotrophic Lateral Sclerosis (ALS) is a progressive disease characterized by the degeneration of upper and lower motor neurons, which consequently leads to paresis of the skeletal and bulbar muscles and can ultimately affect all motor functions, as well as communication and breathing. Life expectancy is between 3 and 5 years after the onset of symptoms. Most patients die from respiratory failure or its complications. ALS is mainly a sporadic disease, however, around 5 to 10% of all cases have a history of autosomal dominant mutations caused by genes such as SOD1, FUS. Its etiology may be implicated in deregulated RNA metabolism, oxidative stress, impaired axonal transport and autophagy. The article aims to carry out a literature review on Amyotrophic Lateral Sclerosis, its etiology and pathophysiological mechanisms, and therapeutic treatments and clinical trials between 2020 and 2025. The scientific databases used were MDPI, Scientific Electronic Library Online (Scielo), National Library of Medicine (NIH), Medline. ALS can be recognized as a complex syndrome that often includes behavioral changes. Diagnosing ALS remains a significant challenge, with little change in the diagnostic approach over the last decade. Despite the increasing use of genetic testing, clinical history and examination are still the main methods of confirming an ALS diagnosis, and it takes between 10 and 16 months from the onset of symptoms to receiving a definitive diagnosis. ALS demonstrates diverse mechanisms in its pathology, such as the involvement of mitochondria from the onset of ALS, manifesting itself not only in the central nervous system (CNS), but also in muscle tissue, as well as oxidative stress that causes diverse lesions. To date, Edaravone and Riluzole, which is a glutamate antagonist, are the only two drugs approved for use in the treatment of ALS, despite their limited beneficial effects on the progression of the disease. Most of the other drugs failed in phase III clinical trials, which were carried out with a larger number of ALS patients. However, there has been an increase in clinical trials and research over the last five years, despite ALS being a disease with a complex pathology, such as the use of human pluripotent stem cells, the CRISPR-9/Cas technique, drugs such as tamoxifen, among others. It is concluded that there are still many limitations in the development and selection of patients and pre-clinical and clinical studies, due to the low incidence and difficulty in making a diagnosis, as well as the presence of different presentations and mutations in its development. Therefore, there is still a need for more extensive research into drugs that can alter the natural history of ALS, prevent its progression and symptoms.