In a recent episode of the Endpoints Podcast, Dr. Theo Hatzipetros, the Director of Pharmacology at the ALS Therapy Development Institute (ALS TDI), discussed the CMAP technique and the role it now plays at the ALS TDI lab. CMAP, which stands for Compound Muscle Action Potentials, is a technique used by neurologists to diagnose neuromuscular diseases and monitor disease progression. Likewise, in mouse models of ALS, CMAP can be used to detect the onset of the disease and track its progression. It is a minimally invasive procedure that involves the insertion of microelectrodes just under the skin of the anesthetized animal. One electrode is used for applying a small electrical current close to a nerve causing it to fire and a second microelectrode is used to measure the resulting electrical activity from the downstream muscles innervated by this nerve. The whole procedure lasts less than fifteen minutes per animal.
Deficits in CMAP are detected well before symptoms of ALS are visible in mice. When using Neuroscore, the traditional way of monitoring disease progression that relies on phenotypic observation, signs of disease in the SOD1 mouse models are typically detected around age day 90. With CMAP deficits are detected as early as age day 50. Thus, CMAP allows researchers to track progression earlier than they would be able to by Neuroscore, and it allows them to determine the efficacy of potential drugs quicker ensuring that the best drug candidates are advanced to the next stages of preclinical development. Furthermore, CMAP performed at age day 50 can be used to reliably predict disease onset and survival rates. Going forward, CMAP may also become a valuable tool in tracking disease progression in non-SOD1 ALS mouse models that do not present a strong phenotype of the disease.
To listen to the full Podcast with Dr. Hatzipetros please visit https://www.als.net/endpoints/72/