Validation of a STMN2-Based Biomarker for ALS Patient Identification and Target Engagement in Clinical Studies
Abstract
QurAlis mission is to use the latest advances in drug design and precision medicine to develop clinically meaningful treatments for ALS that will provide much-needed hope to patients. Cells called motor neurons control movement, and, in ALS, motor neurons become impaired and die, causing muscle weakness and eventual death due to the inability to breathe. In the motor neurons of ALS patients, located in the spinal cord and brain, a protein named TDP-43 mislocalizes and then accumulates, which leads to an imbalance in normal cellular activities and eventual cell death. The significance of this TDP-43 pathology is that it occurs in nearly all ALS patients, including both sporadic and familial forms of the disease. Recent research efforts have identified a connection between TDP-43 mislocalization and a protein that is essential for motor neuron process growth, Stathmin-2 (STMN2). The motor neuron processes connect to muscles to control movement and are crucial to maintaining the health of the entire cell. In ALS, the processes of motor neurons die back and cause fatigue and loss of muscle control. In fact, when the motor neurons that control breathing lose connection with muscles, then the ALS patient goes into respiratory failure. Since STMN2 is usually highly expressed in motor neurons and is critical for neuronal process outgrowth, maintenance, and survival, a number of efforts are underway to block the effect of TDP-43 on STMN2 expression loss that occurs in ALS. If TDP-43 s effect on STMN2 can be blocked then this may restore motor neuron process growth and survival. Restoration of motor neuron function should increase muscle control and improve breathing control in ALS patients. This work will focus on developing assays that can detect changes in STMN2 expression using cerebrospinal fluid or blood samples from patients. The possible uses of these assays include diagnosis, patient identification for clinical trials, and monitoring the effect of therapies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211098
Entities
People
- Sandy Hinckley
Organizations
- United States Army