Advancing Cryogenic Preservation of Functional Platelets for Longevity Research: A Continuation of Ongoing Studies

This project is part of an international consortium funded by the Target ALS Foundation to investigate whether disease-associated forms of the TDP-43 protein accumulate in platelets in ways that parallel ALS pathophysiology in the nervous system. Over a projected three-year, $1.5 million grant period, Agbas’ laboratory at Kansas City University will join three other laboratories in the United States, Switzerland and Italy to analyze blood-derived platelets collected from the same patients living with ALS. The multidisciplinary collaboration will apply complementary technologies across participating labs to determine the most reliable and reproducible method for identifying TDP-43 protein signatures in platelets and to evaluate whether these signatures can serve as accessible, blood-based biomarkers for ALS.

The central scientific question is whether platelet TDP-43 profiles reflect the molecular processes occurring in the nervous system during ALS, and whether platelet-derived measurements can expand the pipeline of therapeutic targets and improve the probability of success in future clinical trials. The KCU team will employ novel monoclonal antibodies to profile TDP-43 in platelet samples, leveraging these reagents to distinguish disease-associated forms of the protein. By comparing data generated with different analytic approaches across the consortium, the project aims to establish standardized, sensitive methods for detecting pathologic TDP-43 in peripheral blood elements.

The consortium’s design—testing platelets from the same cohort of ALS patients with multiple technologies and in multiple laboratories—addresses critical needs in biomarker discovery: reproducibility, cross-platform validation, and clinical relevance. If platelet TDP-43 can be robustly correlated with nervous system pathology or disease progression, it could provide a minimally invasive biomarker for earlier diagnosis, patient stratification in clinical trials, and monitoring of therapeutic responses.

Outcomes of this work could contribute to better diagnostic tools and identify new therapeutic avenues for ALS, addressing an urgent need in a devastating neurodegenerative disease.