A new mouse-model study led by UF neuroscientists lends new insights into factors that could help predict the efficacy of gene therapies using a genetically engineered antibody to target abnormal tau proteins, considered a hallmark of Alzheimer’s disease pathology.
The results, published in the journal Molecular Therapy, compared the disease modifying potential of three different tau-targeting secreted antibody fragments (scFvs), also known as single-chain antibodies, and their related intrabodies (expressed inside the cell). The recombinant antibodies were derived from three well-characterized tau monoclonal antibodies.
The investigators used adeno-associated virus (AAV) technology to express recombinant fragments in the brains and spinal cords of transgenic mice that were overexpressing mutant human tau and showed that phospho-tau specific intrabodies delayed the onset of hindlimb paralysis — a marker of neuronal loss in these mice.
The researchers believe that these findings demonstrate the therapeutic potential of a gene therapy-based approach to targeting tau with recombinant antibodies and highlight the need for continued optimization of this approach.
The study was led by a UF team including Yona Levites, Ph.D., a research associate professor of neuroscience; Marshall Goodwin, Ph.D., a postdoctoral fellow of neuroscience; and Todd Golde, M.D., Ph.D., a professor of neuroscience and director of the McKnight Brain Institute.