Neuraltus Pharmaceuticals of Palo Alto, Calif., is developing a small molecule whose target is regulation of immune system cells believed to contribute to neuroinflammation and disease progression in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).
About ALS mechanisms
ALS is a disease in which motor neurons — nerve cells in the brain and spinal cord that control voluntary muscle movement — die, causing progressive paralysis and death, usually within three to five years.
About 10 percent of the time, ALS is familial (inherited), showing a clear family history, and results from any of a number of defects in several known and some as-yet-unrecognized genes. The other 90 percent of the time, the cause of ALS is unknown, and the disease occurs without any family history ("sporadically").
A growing body of evidence points to malfunction of the immune system as at least part of the complex ALS disease process. As noted in previous study reports, abnormal immune system activity has been observed in animal models of the disease; it also has been found in blood samples of people with ALS.
'There's a switch'
NP001 is administered by intravenous injection.
According to Andrew Gengos, president and CEO of Neuraltus, the company's experimental drug is designed to flip a molecular switch in cells known as macrophages in the blood and microglia in the central nervous system.
"There's a switch that it hits," Gengos said, "that regulates these cells from an activated, inflammatory mode back to a more normal, wound-healing mode." (For more about this phenomenon, see ALS: Not Just About Motor Neurons Anymore, in the May-June 2010 ALS Newsmagazine.)
Mice with an SOD1 mutation called G93A are a common research model of the human disease and were used in the Neuraltus experiments.
Meaning for people with ALS
Neuraltus is currently completing mouse studies that it hopes will show its compound changes the immune system and affects progression of ALS. If the results show the anticipated effect, they will add to the increasingly large body of evidence that shows that parts of the immune system go awry in ALS.
If all goes as planned, the company hopes to conduct a phase 1 safety trial of NP001 in people with ALS by the fall of 2010.