Clinical trial for antisense oligonucleotide therapy in a patient with ADLD

Awardee: Margot Cousin

Institution: Mayo Clinic

Grant Amount: $50,000

Funding Period: May 1, 2023 - April 30, 2024

Summary: The long-term research goal is to advance disruptive innovation to transform care for individuals with ADLD through the development of a translational therapeutics program using team science. We hypothesize that a gapmer ASO to knockdown LMNB1 expression will be safe and well tolerated and that it will ultimately improve clinical outcomes in patients with ADLD. The objectives in this application are to develop and execute a first-in-human clinical trial to determine safety, tolerability, and potential clinical benefit of an LMNB1-targeted ASO therapy in a single patient with ADLD.

Development of 3D ADLD microfiber and organoid models for studying biomarkers and drug testing

Awardee: Stefano Ratti

Institution: University of Bologna

Grant Amount: $50,000

Funding Period: May 1, 2023 - April 30, 2024

Summary: The project aims at developing reliable ADLD microfiber and organoid models for investigating
biomarkers and for drug testing. The novel models to be developed with this substantial 1 -year funding include 3D microfiber co-cultures of astrocytes and oligodendrocyte precursors (OPCs) and brain organoids. These models will be created from the fibroblasts of patients with the LMNB1 gene duplication and deletion phenotypes and healthy donors.  

Analyzing CNS cell type specific transcriptomics in ADLD

Awardee: Quasar Padiath

Institution: University of Pittsburgh

Grant Amount: $50,000

Funding Period: May 1, 2023 - April 30, 2024

Summary: In this proposal, ADLD brain tissue samples will be utilized to carry out both bulk and
CNS cell type specific transcriptomics (RNA Seq analysis). Such an analysis will identify pathways there are perturbed as a result of lamin B1 overexpression and interrogate lamin B1 overexpression across different CNS cell types. These studies will help identify pathways contributing to the demyelination phenotype that may serve as potential therapeutic targets. In addition, cell type specific analysis can identify cells that are targeted for lamin B1 overexpression and cell type specific pathways that are perturbed providing critical insights into which cell types are responsible for the disease process.