Pharmacotherapy for Amyotrophic Lateral Sclerosis: A Review of Approved and Upcoming Agents

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder involving loss of upper and lower motor neurons, with most cases ending in death within 3-5 years of onset. Several molecular and cellular pathways have been identified to cause ALS; however, treatments to stop or reverse disease progression are yet to be found. Riluzole, a neuroprotective agent offering only a modest survival benefit, has long been the sole disease-modifying therapy for ALS. Edaravone, which demonstrated statistically significant slowing of ALS disease progression, is gaining approval in an increasing number of countries since its first approval in 2015. Sodium phenylbutyrate and taurursodiol (PB-TURSO) was conditionally approved in Canada in 2022, having shown significant slowing of disease progression and prolonged survival. Most clinical trials have focused on testing small molecules affecting common cellular pathways in ALS: targeting glutamatergic, apoptotic, inflammatory, and oxidative stress mechanisms among others. More recently, clinical trials utilizing stem cell transplantation and other biologics have emerged. This rich and ever-growing pipeline of investigational products, along with innovative clinical trial designs, collaborative trial networks, and an engaged ALS community', provide renewed hope to finding a cure for ALS. This article reviews existing ALS therapies and the current clinical drug development pipeline

Interplay between immunity and amyotrophic lateral sclerosis: Clinical impact

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. The aim of this manuscript is to summarize the recent advances regarding the immune system involvement in ALS, with particular attention to clinical translation. We focus on the potential pathophysiologic mechanism of the immune system in ALS, discussing local and systemic factors (blood, cerebrospinal fluid, and microbiota) that influence ALS onset and progression in animal models and people. We also explore the potential of Positron Emission Tomography to detect neuroinflammation in vivo, and discuss ongoing clinical trials of therapies targeting the immune system. With validation in human patients, new evidence in this emerging field will serve to identify novel therapeutic targets and provide realistic hope for personalized treatment strategies

Interplay between immunity and amyotrophic lateral sclerosis: Clinical impact

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. The aim of this manuscript is to summarize the recent advances regarding the immune system involvement in ALS, with particular attention to clinical translation. We focus on the potential pathophysiologic mechanism of the immune system in ALS, discussing local and systemic factors (blood, cerebrospinal fluid, and microbiota) that influence ALS onset and progression in animal models and people. We also explore the potential of Positron Emission Tomography to detect neuroinflammation in vivo, and discuss ongoing clinical trials of therapies targeting the immune system. With validation in human patients, new evidence in this emerging field will serve to identify novel therapeutic targets and provide realistic hope for personalized treatment strategies