The diversification of potential donors to perform stem cell allografts now enables to propose a compatible graft cell source adapted to the different clinical situations. Transplants with a geno-identical sibling donor, otherwise with the most HLA-compatible unrelated donor, remain the first-line solutions. Alternative transplants allow to graft patients having no donors in international registries, owing to the rarity of their HLA typing. They are carried out with fairly incompatible grafts and are therefore limited by the existence in the recipient of preformed anti-HLA antibodies which predispose to their rejection. The simple prevention of acute Graft-versus-host disease in haplo-identical transplants, as well as the availability of donors, explain why they have very often replaced placental stem cell transplants. These latter remain useful for pediatric patients or in the absence of family donors.
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http://dx.doi.org/10.1016/j.tracli.2017.06.006 | DOI Listing |
Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Background: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFBackground: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.
Alzheimers Dement
December 2024
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.
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