"Stathmin-2: An Emerging Therapeutic Target in TDP-43 Proteinopathies"

Clotilde Lagier-Tourenne, MD, PhD gives her presentation

Abnormal protein accumulations of the RNA binding protein TDP-43 are found in almost all instances of amyotrophic lateral sclerosis (#ALS), 45% of frontotemporal dementia (FTD), and 30% of Alzheimer’s disease patients. TDP-43 aggregations are associated with a striking nuclear loss of the protein. Dr. Lagier-Tourenne and her team recently demonstrated that the human RNA most affected by loss of nuclear TDP-43 is encoding the neuronal growth-associated factor called stathmin-2. Reduced levels in stathmin-2 is a hallmark in sporadic and familial ALS/FTD, and restoration of stathmin-2 expression emerges as an attractive therapeutic strategy in TDP-43 proteinopathies. Using newly generated cellular and animal models, Dr. Lagier-Tourenne and her team determined stathmin-2’s essential role for neuronal regeneration and axonal maintenance and have established antisense oligonucleotides (ASOs) as a therapeutically viable approach to rescue stathmin-2 in TDP-43 proteinopathies.