Heart Drug Used To Control Heartbeat May Treat Lou Gehrig's Disease
Scientists searching for a cure for the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS) have hit upon a novel idea to stop the progression of the disease: using the heart drug Digoxin.
Digoxin is a common drug used to treat atrial fibrillation and atrial flutter, which cause irregular heartbeats. When researchers from Washington University's School of Medicine in St. Louis used it to block a particular enzyme known to promote ALS, the condition's progression stopped. The enzyme, called sodium-potassium ATPase, was accidently discovered when scientists were looking into the effects of another protein, the mutated version of which is known to cause an inherited disease similar to ALS in mice — it's also characterized by paralysis. The results were published in the journal Nature Neuroscience on Sunday.
The scientists discovered this mutated sodium-potassium ATPase in mice when studying their brains' stress responses. The main function of the protein is to pump charged sodium particles out of cells while pulling charged potassium particles in. This allows cells to maintain an electrical charge across their outer membrane. A proper balance in the electromagnetic charge is crucial for cells to function properly. In these studies, the researchers concentrated on the role of ATPase in brain cells called astrocytes.
In mice with ALS, the astrocytes were found to have levels of ATPase far higher than normal. They also found that when the enzyme's levels increased, the astrocytes released harmful chemicals called inflammatory cytokines, which caused death to motor neurons.
Previous studies have suggested that astrocytes are linked to the development of neurodegenerative diseases beyond ALS, such as Alzheimer's, Huntington's, and Parkinson's. Lab experiments have also shown that astrocytes from mice with ALS destroyed healthy motor neurons when placed in petri dishes. Though it's unclear how this happens, the researchers believe ATPase plays a central role. They came to this conclusion after blocking the enzyme — or limiting its ability to make copies of the enzyme — and finding that the destruction of nerve cells stopped. "We blocked the enzyme with digoxin," senior author Azad Bonni 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 heart drug is believed to incite a balance in the enzyme's sodium and potassium levels. In the experiment, mice that had only one copy of the gene for sodium-potassium ATPase had lower levels of the enzyme produced. Because of that, the mice survived 20 days longer than those that had two copies of the gene. "The mice with only one copy of the sodium-potassium ATPase gene live longer and are more mobile," Bonni said. "They're not normal, but they can walk around and have more motor neurons in their spinal cords."
While the research is still in its early stages, it could be the starting point for future studies looking to unravel the mysteries of neurodegenerative diseases. ALS Affects more than 5,600 Americans each year.
Source: Robertson J, Steen H, Bonni A, et al. An alpha2- Na/K ATPase/alpha-adducin complex in astrocytes triggers non-cell autonomous neurodegeneration. Nature Neuroscience. 2014.