MLD publishes world's first chronic plasmalogen-deficient Alzheimer's mouse model
MLD is excited to announce that it has published the creation of the first plasmalogen-based Alzheimer’s disease mouse model. The novel model is based on a chronic plasmalogen deficiency that can be induced during adulthood, accurately mimicking the plasmalogen deficiency that occurs as a function of age in Alzheimer’s disease. The creation and initial characterization of the model was accepted for publication in Brain Research.
Plasmalogen deficiency has been correlated with neurodegenerative diseases for decades, with support growing for the hypothesis that plasmalogen deficiency might drive the onset and progression of Alzheimer’s disease. MLD is the world-leader in the development of therapeutic-grade synthetic plasmalogen precursors and has worked for years to support the causal link between plasmalogens and Alzheimer’s. Confirming this hypothesis was previously impossible due to the lack of a suitable animal model displaying a chronic plasmalogen deficiency later in life. MLD therefore developed this missing model using CRISPR technology to generate a tamoxifen-inducible knockout of Gnpat, the first enzyme in the plasmalogen biosynthetic pathway. Upon tamoxifen administration, animals undergo a genetic recombination event which causes the loss of Gnpat function, resulting in significant reductions in plasmalogen levels in both the circulation and tissues in as little as four weeks after the recombination event. More exciting is the observation that after only four months of plasmalogen deficiency, animals showed changes in behavior and nerve function.
“This model represents a huge jump forward in our understanding of the role of plasmalogens in vivo and how they could be behind the changes seen in Alzheimer’s. For the first time we can see what happens when an individual acquires a plasmalogen deficiency in adulthood” says Dr. Tara Smith, Executive VP, Innovative Therapies and lead author of the paper.
The animals were shown to display an increased level of activity and changes in nerve conduction physiology that correlated with plasmalogen levels. These changes have previously been described in full knockout models of plasmalogen deficiency which are designed based on the disease Rhizomelic chondrodysplasia punctata (RCDP), an ultra-rare pediatric disorder which results in significant neurological and physical impairments, as well as severely reduced life expectancy. Previously, it was unclear if the behavioral and functional differences in RCDP mouse models were strictly caused by developmental impairments.
MLD intends to continue the characterization of this model and evaluate the ability of its proprietary synthetic plasmalogen precursors to prevent or rescue the biochemical, behavioral, and functional consequences of plasmalogen deficiency.
“This model and findings represent a landmark advancement in the field of plasmalogen research and Alzheimer’s disease. Until now, the lack of this model was a major roadblock in the development of credible plasmalogen-based therapeutic solutions for all chronic conditions associated with a plasmalogen deficiency. Our ongoing characterization of this model will continue to provide unparalleled insights in to the role of plasmalogens in the brain, and will be an invaluable tool as we continue to lead the field in the development of clinical-grade plasmalogens for numerous therapeutic indications,” commented Dr. Shawn Ritchie, CEO and Chief Scientific Officer.
To click here to see the full article: A novel inducible animal model for studying chronic plasmalogen deficiency associated with Alzheimer’s Disease
About MLD:
MLD is a biopharma company in Saskatoon, SK, Canada that is the world-leader in the development of synthetic plasmalogen precursors for conditions associated with plasmalogen deficiency including RCDP and Alzheimer’s disease.