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Drug Development.
Alzheimers Dement
December 2024
University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
Background: Pharmacoepidemiologic studies assessing drug effectiveness for Alzheimer's disease and related dementias (ADRD) are increasingly popular given the critical need for effective therapies for ADRD. To meet the urgent need for robust dementia ascertainment from real-world data, we aimed to develop a novel algorithm for identifying incident and prevalent dementia in claims.
Method: We developed algorithm candidates by different timing/frequency of dementia diagnosis/treatment to identify dementia from inpatient/outpatient/prescription claims for 6,515 and 3,997 participants from Visits 5 (2011-2013; mean age 75.
Background: The therapeutic management of dementia with Lewy bodies (LBD) is a challenge given the high sensitivity to drugs in this disease. This is particularly sensitive with regard to the management of parkinsonism. In particular, treatment of motor symptoms with levodopa or dopaminergic agonists poses a risk of worsening cognitive and behavioral symptoms.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Henan Academy of Innovations in Medical Science, Zhengzhou, Henan, China.
Background: Glucagon-like peptide 1 (GLP-1) is a peptide hormone that plays several physiological roles in treating diabetes and in protecting the brain. Recent clinical trials testing 4 different GLP-1 class drugs in phase 2 trials showed a clear correlation between neuroprotection and the ability to cross the BBB. Exenatide and Lixisenatide both showed excellent protective effects in patients Parkinson's disease (PD) and both drugs can readily cross the BBB.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
Drug Development.
Alzheimers Dement
December 2024
Karolinska Institute, Stockholm, Södermanland and Uppland, Sweden.
Background: Novel anti-amyloid therapies (AAT) for Alzheimer's Disease (AD) have recently been approved in the United States, Japan and China, and are under regulatory review in Europe. Questions remain regarding the long-term effectiveness and value of these drugs when used in routine clinical practice. Data from follow-up studies will be important to inform their optimal use, including criteria for treatment initiation, monitoring strategies, stopping rules, pricing and reimbursement considerations.
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