A drug used in the treatment of heart failure may be able to treat amyotrophic lateral sclerosis, according to a recent study.
Researchers at the Washington University School of Medicine in St. Louis found that Digoxin may be adaptable for the treatment of amyotrophic lateral sclerosis (ALS), a progressive, paralyzing disease.
ALS, also known as Lou Gehrig's disease, destroys the nerve cells that control muscles. This leads to loss of mobility, difficulty breathing and swallowing and eventually death. Riluzole, the sole medication approved to treat the disease, has only marginal benefits in patients.
The research team found that when they reduced the activity of an enzyme or limited cells' ability to make copies of the enzyme, the disease's destruction of nerve cells stopped. The enzyme maintains the proper balance of sodium and potassium in cells.
"We blocked the enzyme with digoxin," Azad Bonni, senior author of the study, said in a statement. "This had a very strong effect, preventing the death of nerve cells that are normally killed in a cell culture model of ALS."
The results stemmed from Bonni's studies of brain cells' stress responses in a mouse model of ALS. The mice have a mutated version of a gene that causes an inherited form of the disease and develop many of the same symptoms seen in humans with ALS, including paralysis and death.
Efforts to monitor the activity of a stress response protein in the mice unexpectedly led the scientists to another protein: sodium-potassium ATPase. This enzyme ejects charged sodium particles from cells and takes in charged potassium particles, allowing cells to maintain an electrical charge across their outer membranes.
Maintenance of this charge is essential for the normal function of cells. The particular sodium-potassium ATPase highlighted by Bonni's studies is found in nervous system cells called astrocytes. In the ALS mice, levels of the enzyme are higher than normal in astrocytes.
Bonni and his colleagues found that the increase in sodium-potassium ATPase led the astrocytes to release harmful factors called inflammatory cytokines, which may kill motor neurons.
Many important questions remain about whether and how inhibitors of the sodium-potassium ATPase enzyme might be used to slow progressive paralysis in ALS, but Bonni said the study offers an exciting starting point for further studies.
The findings appear online Oct. 26 in Nature Neuroscience.
