Staging System In ALS Shows Potential Tracks Of Disease Progression
"Researchers at Penn and beyond can now start to investigate and try to confirm this transmission process in ALS, by looking for cell to cell transmission of TDP-43 in models of ALS," said senior author John Trojanowski, MD, PhD, director of the Penn Institute on Aging and professor of Pathology and Laboratory Medicine at Penn. "If this transmission process can be identified and understood in ALS, this opens a new pathway for treatments, such as immunotherapies that could interrupt or block damaged and destructive proteins from corrupting other cells, thus halting the spread of disease."
Researchers examined 76 autopsies of patients with ALS, measured pathological TPD-43 distribution and concentration in the nervous system, and were able to map out four distinct stages to assess the disease and burden of pathology.
- In stage 1, TDP-43 pathology was found within the primary motor cortex, as well as neurons in the spinal cord and nerves in the brainstem involved with swallowing, breathing and movement.
- Stage 2 added to stage 1, with TDP-43 progressing forward in the brain and into brainstem areas important for balance and posture.
- In stage 3, TDP-43 pathology moved further forward in the frontal cortex and also to areas just behind the primary motor cortex.
- By stage 4, TDP-43 lesions spread more widely to the temporal lobe and hippocampus, areas involved in memory and language comprehension.
The information gathered in these post-mortem autopsies mirrors what neurologists see in patients clinically. Future efforts may interrogate the process of disease progression further, work to identify biomarkers that can help detect the burden of disease in patients during life, and, most importantly, home in on therapies to arrest the progression of ALS.