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Antioxidant Drug Approved for ALS

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Abstract

A drug that was approved 2 years ago in Japan and South Korea for patients with amyotrophic lateral sclerosis (ALS) now is FDA approved for the same indication. Edaravone is the first ALS drug to gain approval since the agency sanctioned riluzole in 1995.

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... Indeed, oxidative stress is a predominant mechanism of injury in cisplatin-induced AKI 8,25 . We used the slightly hydrophobic scavenger edaravone, which is approved in the U.S. for ALS and in Japan for ischemic stroke and ALS 26,27 . We found that edaravone-loaded MNPs imparted substantial protection against CI-AKI as measured by renal function, histology, and oxidative stress levels. ...
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Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. In our prior work, we developed a highly-selective kidney-targeted mesoscale nanoparticle (MNP) that accumulates primarily in the renal proximal tubular epithelial cells while exhibiting no toxicity. Here, we found that MNPs exhibit renal-selective targeting in multiple mouse models of tumor growth with virtually no tumor accumulation. We then evaluated the therapeutic efficacy of MNPs loaded with the reactive oxygen species scavenger edaravone in a mouse model of CI-AKI. We found a marked and significant therapeutic effect with this approach as compared to free drug or empty control MNPs, including improved renal function, histology, and diminution of oxidative stress. These results indicated that renal-selective MNP edaravone delivery holds substantial potential in the treatment of acute kidney injury among patients undergoing cisplatin-based chemotherapy.
Chapter
This eighth edition of Dr Reichel's formative text remains the go-to guide for practicing physicians and allied health staff confronted with the unique problems of an increasing elderly population. Fully updated and revised, it provides a practical guide for all health specialists, emphasizing the clinical management of the elderly patient with simple to complex problems. Featuring four new chapters and the incorporation of geriatric emergency medicine into chapters. The book begins with a general approach to the management of older adults, followed by a review of common geriatric syndromes, and proceeding to an organ-based review of care. The final section addresses principles of care, including care in special situations, psychosocial aspects of our aging society, and organization of care. Particular emphasis is placed on cost-effective, patient-centered care, including a discussion of the Choosing Wisely campaign. A must-read for all practitioners seeking practical and relevant information in a comprehensive format.
Article
Full-text available
Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.
Chapter
Nanomedicines, nanotechnologies applied to medicine, have been in clinical use for 25 years because of their potential to improve the therapeutic index of drugs. Nanotechnologies can also broaden the classes of therapies that can be administered to patients. They have been used in drug delivery strategies to improve drug bioavailability, solubility, stability, and tolerability, among other benefits. Nanoparticles can also enable the use of nucleic acid therapies and other macromolecular drugs by encapsulating normally delicate cargoes. While the majority of nanoparticles localize drugs predominantly to the liver or spleen, a bevy of recent progress has focused on targeting to the kidneys. This chapter focuses on the advances in drug delivery strategies for the treatment of renal diseases, including methods to improve drug specificity to the nephron. We highlight recent preclinical and clinical developments in nanomedicines and their potential for advancement in nephrology.
Article
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that always affects the respiratory muscles. It is characterized by degeneration of motor neurons in the brain and spinal cord. Respiratory complications are the most common causes of death in ALS and typically occur within 3 to 5 years of diagnosis. Because ALS affects both upper and lower motor neurons, it causes hyperreflexia, spasticity, muscle fasciculations, muscle atrophy, and weakness. It ultimately progresses to functional quadriplegia. ALS most commonly begins in the limbs, but in about one-third of cases it begins in the bulbar muscles responsible for speech and swallowing.
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