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International Journal of Molecular... Feb 2022Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.
Topics: Amyotrophic Lateral Sclerosis; Combined Modality Therapy; Deep Brain Stimulation; Drug Discovery; Edaravone; Humans; Induced Pluripotent Stem Cells; Riluzole
PubMed: 35269543
DOI: 10.3390/ijms23052400 -
The American Journal of Managed Care Dec 2017This activity will update pharmacists and other healthcare professionals on current treatments for pseudobulbar affect (PBA). Points of discussion will focus on the... (Review)
Review
This activity will update pharmacists and other healthcare professionals on current treatments for pseudobulbar affect (PBA). Points of discussion will focus on the off-label therapies traditionally used to treat PBA, the FDA-approved combination drug product with PBA as an indication, and managed care aspects of treating PBA.
Topics: Antidepressive Agents, Tricyclic; Drug Approval; Drug Therapy; Drugs, Investigational; Female; Humans; Male; Medication Therapy Management; Patient Safety; Pseudobulbar Palsy; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 29297657
DOI: No ID Found -
Aging Brain 2021Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular... (Review)
Review
Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular atrophy, primary lateral sclerosis, and pseudobulbar palsy. Even though endocrine dysfunction independently impacts the ALS-related survival rate, the complex connection between ALS and the endocrine system has not been studied in depth. Here we review earlier and recent findings on how ALS interacts with hormones of the hypothalamus and pituitary gland, the thyroid gland, the pancreas, d) the adipose tissue, e) the parathyroid glands, f) the bones, g) the adrenal glands, and the gonads (ovaries and testes). Of note, endocrine issues should always be explored in patients with ALS, especially those with low skeletal muscle and bone mass, vitamin D deficiency, and decreased insulin sensitivity (diabetes mellitus). Because ALS is a progressively deteriorating disease, addressing any potential endocrine co-morbidities in patients with this malady is quite important for decreasing the overall ALS-associated disease burden. Importantly, as this burden is estimated to increase globally in the decades to follow, in part because of an increasingly aging population, it is high time for future multi-center, multi-ethnic studies to assess the link between ALS and the endocrine system in significantly larger patient populations. Last, the psychosocial stress experienced by patients with ALS and its psycho-neuro-endocrinological sequelae, including hypothalamic-pituitaryadrenal dysregulation, should become an area of intensive study in the future.
PubMed: 36911507
DOI: 10.1016/j.nbas.2021.100024