Reassessing Amyloid Modulation: Clinical Efficacy and Safety of Valiltramiprosate in Alzheimer's Disease
Purvi Kaurani1, Shikha Gupta2, krishna Patidar3, Bhavana Metukuru4, Amit Joshi5, Tanishka M6, Parvin Mozafari7, N/A Srijamya8
1D.Y. Patil University School of Medicine, 2Fortis Hospital, 3Jinan University School of Medicine, 4Government Medical College, 5Chongqing Medical University, 6ACS Medical College and Hospital, 7Faculty of Medicine, University of Georgia, 8Ivane Javakhishvili Tbilisi State University
Objective:
This study seeks to evaluate the efficacy and safety of Valiltramiprosate (ALZ-801) in Alzheimer's disease (AD) by emphasizing on cognitive and functional performance, brain volume changes, adverse effects and responses to the Apolipoprotein E4 (APOE e4) allele.
Background:
Alzheimer's disease is a progressive neurodegenerative disorder caused by abnormal protein deposition in the brain. Its prevalence in the world is 9.8 million, as of 2021. APOE e4 allele is a genetic determinant that precipitates accumulation of beta-amyloid protein, therefore predisposing an individual with two copies of the allele to early-onset AD. Valiltramiprosate (ALZ-801) is an oral drug that prevents neurotoxic beta-amyloid oligomer formation, potentially serving as a disease modifying treatment.
Design/Methods:
This study reviews APOLLOE4 trial findings assessing the safety and efficacy of ALZ-801 in AD. AD Assessment Scale-Cognitive Subscale [ADAS-Cog13] and Clinical Dementia Rating-Sum of Boxes [CDR-SB] were used to measure cognitive improvement. Diffuse tensor imaging of hippocampus and Amyloid-related imaging abnormalities (ARIA) was conducted along with Disability Assessment for Dementia (DAD).
Results:
Treatment with ALZ-801 in the early AD population showed 18% hippocampal atrophy slowing but no significant improvement in cognitive performance. The mild cognitive impairment (MCI) subgroup, however, demonstrated enhanced cognitive functioning as shown by a 52% improvement on the ADAS- Cog13 test. Functional evaluation showed positive results of 96% and 102% on DAD and CDR-SB scores respectively, indicating improved functional abilities. MCI group exhibited 26% decrease in hippocampal atrophy. Commonly reported adverse effects included nausea, vomiting and loss of appetite, with no evidence of brain edema or hemorrhages.
Conclusions:
Studies for ALZ-801 in early AD population showed no notable clinical efficacy in the overall study population at 78 weeks. Nevertheless, the MCI subgroup reported significant reduction in brain atrophy progression and functional decline. No increase in ARIA or serious adverse events were evident, highlighting the safety and tolerability of the drug.
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