Brain-penetrant TTBK1 inhibitors reduce TDP-43 pathology and improve cognition in a mouse model
Original source
Selective Brain-Penetrant TTBK1 Inhibitors Modulate TDP-43 Pathology and Rescue Cognitive Deficits in a Mouse Model of TDP-43 Proteinopathy. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human, Mouse
Related topics
Researchers developed selective TTBK1 inhibitors that reached the brain and reduced phosphorylated TDP-43 in cells and patient-derived frontotemporal dementia models. In mice with TDP-43 proteinopathy, the lead compound improved cognitive performance, protected the frontal cortex and reduced microglial activation.
Why this matters
TDP-43 pathology is associated with amyotrophic lateral sclerosis and frontotemporal dementia, making it a potential target for disease-modifying treatments. However, these results are from laboratory models and do not yet show that the compounds are safe or effective in people with ALS or frontotemporal dementia.
Limitations and context
The study tested compounds in cells, patient-derived models and mice, not in people. The findings therefore do not establish a treatment benefit for ALS or frontotemporal dementia, and further research would be needed to assess safety and effectiveness in humans.