Naturally Occurring Enzyme Improves ALS Symptoms in Mice, Study Shows

A naturally occurring enzyme improves ALS symptoms in mice and could lead to effective therapies in humans, a study suggests.

The research, “Deletion of NAMPT in Projection Neurons of Adult Mice Leads to Motor Dysfunction, Neurodegeneration, and Death,” appeared in the journal Cell Reports.

Data from the ALS Registry indicated that the prevalence of ALS in the United States was about five cases per 100,000 persons in 2013. This would translate into 14,000 to 15,000 Americans with the disease.

ALS is a progressive movement disability condition characterized by death of nerve cells. Patients initially exhibit weakness in legs, feet, and hands. This spreads to other parts of the body and leads to muscle atrophy, difficulty walking and swallowing, and slurred speech.

“Our previous studies indicated that an enzyme known as NAMPT (nicotinamide phosphoribosyltransferase) is primarily expressed in the neurons [nerve cells] in mouse models, and overexpression of NAMPT can protect against further brain injury following a stroke. For these reasons, NAMPT became a good target of study,” Shinghua Ding, the study’s senior author, said in a press release. He is with the University of Missouri’s Dalton Cardiovascular Research Center.

The Nampt gene codes for the NAMPT enzyme. Researchers discovered that deleting the gene in the central nervous system of mice engineered to have ALS led to the animals developing symptoms similar to humans with the disease — loss of weight, drop in body temperature, degeneration of cells that control movement, and loss of movement capability.

At the cell level, deleting the Nampt gene impaired the functioning of mitochondria, the cells’ power plants. It also led to muscle atrophy and defective communication at neuromuscular junctions, which as the name implies is where nerve cells and muscles come together. Lack of the NAMPT enzyme ultimately led to paralysis and death, researchers said.

The team then treated mice with nicotinamide mononucleotide, a naturally occurring molecule that regulates NAMPT activity. It served as a substitute for NAMPT,  reducing loss of movement capability and increasing the lifespan of NAMPT-deficient mice.

In ALS patients, levels of NAMPT are significantly lower in spinal cord cells, supporting the notion of a link between ALS and NAMPT.

“Our data from human ALS subjects potentially link NAMPT to ALS,” the researchers wrote.

“What we’ve shown is that NAMPT is essential to neuronal function and viability,” Ding said. “Based on our findings, it is an ideal candidate for further study, and the possible development of drugs in the diagnosis and treatment of ALS and stroke victims.”