Does the accumulation of disease-associated forms of TDP-43 in platelets parallel ALS pathophysiology in the nervous system?

This study seeks to investigate whether disease-associated forms of the protein TDP-43 accumulate in platelets in a way that parallels ALS pathophysiology in the nervous system. It will analyze TDP-43 protein profiles using novel monoclonal antibodies applied to platelets obtained from people currently living with ALS. Agbas’ laboratory at KCU will join three other laboratories in the United States, Switzerland, and Italy. Each lab will apply different technologies to the same set of blood-derived platelets from the same patients, allowing cross-comparison of methods and identification of the most robust approach for detecting TDP-43 species in platelets.

The consortium’s work is motivated by a need to expand the pipeline of therapeutic targets and improve the probability of success in clinical trials for ALS. By focusing on blood-derived platelets, the project explores a minimally invasive source of material that may reflect neurodegenerative processes. This project will bring the consortium an ongoing line of investigation into TDP-43 in platelets that has advanced to the level of a submitted patent application. The group will study how TDP-43 behaves prior to becoming diseased, aiming to detect disease-associated forms or profiles that could serve as biomarkers or inform therapeutic development.

Over the projected three-year funding period, the collaborators will compare technologies and analytical strategies to determine which methods most reliably identify TDP-43 protein species in platelets. Working with platelets has not been thoroughly explored to date and expressed hope that the consortium’s coordinated effort will yield valuable information to aid diagnosis and treatment of ALS. The consortium’s design—analyzing platelets from the same patients across multiple laboratories—supports rigorous validation and method benchmarking, which are critical steps for translating candidate biomarkers into clinical tools.

The grant provides opportunities beyond laboratory discovery. Students from KCU’s College of Osteopathic Medicine and College of Biosciences will have the chance to participate in the research, gaining hands-on experience in a multi-institutional project that links basic protein science, biomarker development, and translational goals. Collectively, the consortium aims to establish the best method for identifying TDP-43 in platelets and to determine whether platelet TDP-43 profiles parallel what is seen in the nervous system during ALS, thereby informing future diagnostic strategies and therapeutic target selection.