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Clinical Pharmacy Practice Parthasarathy Pdf 121 (April-2022)




(Bachelor of Pharmacy, The Rajiv Gandhi University of Health Sciences, Hyderabad, India; Masters of Pharmacy, Harvard University, Cambridge, MA, USA; Ph.D. in Pharmaceutical Sciences, The University of Texas at Austin, Austin, TX, USA) Senior Scientist and Vice President, R&D, NeuroLife Sciences, Inc., West Orange, NJ, USA. R Cremo. (Professor, Program in Molecular Biology, The University of Texas at Austin, Austin, TX, USA) Associate Professor, Clinical Pharmacy Practice, College of Pharmacy, The Ohio State University, Columbus, USA. A Ramarao. (Associate Professor, Department of Pharmaceutical Sciences, The University of Texas at Austin, Austin, TX, USA) Abstract Current approaches for the identification and development of new drugs to treat neurodegenerative disorders including Alzheimer’s disease (AD) have shown limited success. The imbalance between protein synthesis and degradation in AD is a key feature of the disease. We describe a new investigational drug ALZ-801 that promotes the clearance of the AD-linked protein, amyloid-β peptide (Aβ) by activating the ubiquitin proteasome system (UPS). An oral small molecule, ALZ-801, inhibited degradation of APP and Aβ40, Aβ42 peptides, and Aβ oligomers in cell-based systems. Dosing in APP transgenic mice reduced Aβ and α-synuclein (α-syn) deposition, as well as tau pathology. In the aged YAC-120 tau transgenic mice, dosing with ALZ-801 decreased tau pathology and improved cognitive function. ALZ-801, at clinically relevant dosages, delayed the onset and slowed the progression of disease in preclinical AD models, including the Tg2576 and APP/PS1 mouse models and the cynomolgus monkey model. In contrast to other therapies for AD, no behavioral or neurological symptoms were observed with ALZ-801 in a 14-month study. These studies demonstrate that ALZ-801 can promote protein clearance by activating the UPS in AD and that further study of ALZ-801 may lead to the development of a disease-modifying treatment for AD. Introduction Alzheimer’s disease (AD) is the most common neurodegenerative disease and is a major cause of dementia. It is characterized by the progressive accumulation of extracellular deposits





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Clinical Pharmacy Practice Parthasarathy Pdf 121 (April-2022)
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