Multiple sclerosis is not a single condition, but an ebbing and flowing of stages affecting the body's central nervous system.
Recognizing that pattern, researchers from the Stanford University School of Medicine have identified therapy targets that could lead to personalized treatments for patients at each phase of the illness.
Essentially, the team cataloged all of the brain-tissue proteins that they found were distinct to three discrete stages of multiple sclerosis.
“ This is a gold mine, ” said Lawrence Steinman, MD, professor of neurology and neurological sciences. “ Knowing what proteins are most important at a discrete stage of the multiple sclerosis process is the first step toward being able to ‘ personalize ' treatment. ”
Steinman, whose team worked with researchers at the University of Connecticut Health Center, is one of two senior authors of the article that will be published in the Feb. 17 issue of the journal Nature.
In the study, the team found many unexpected proteins involved in the disease progression. When they tested drugs that block two of these proteins in a mouse model of multiple sclerosis, the mice improved dramatically.
“ If our hypothesis is correct, the findings can be directly applied to patients, ” said May Han, MD, a postdoctoral scholar at Stanford and co-first author of the paper. She emphasized that researchers are still very early in the process of being able to tailor drug therapies for humans.
In multiple sclerosis, the immune system launches an attack against the myelin sheath surrounding nerve cells, causing them to misfire. The resulting variety of neurological disorders affects more than 2.5 million people worldwide, according to the Multiple Sclerosis International Federation.
When Han arrived to work in Steinman ' s lab, she suggested studying the amazing repository of multiple sclerosis brain samples still being stored in the lab freezer. The samples had come from Cedric Raine, MD, professor of pathology and of neurology at the Albert Einstein College of Medicine, who had collaborated six years ago with Steinman. Raine had obtained the samples from autopsies of patients with various stages of multiple sclerosis, and he had supplied a detailed analysis of the abnormalities.
Han proposed a novel idea: to use these carefully characterized slices to identify the protein changes between three major types of multiple sclerosis lesions seen upon autopsy — plaques from the acute stage (recent inflammation and damage to myelin), the chronic-active stage (long-term myelin damage and areas of recent inflammation) and the chronic-silent stage (no current inflammation).
Steinman recalled telling Han that it was a great idea, but that his lab didn ' t do proteomics, which is the large-scale study of protein structure and function. But Han had a secret weapon: Her brother, David Han, PhD, directs a proteomics analysis facility at the University of Connecticut Health Center. He is the other senior author of the paper.
They identified more than 1,000 different proteins in each stage, creating the largest catalog of multiple sclerosis brain lesions to date. The enormous list of proteins became a bottleneck for the researchers. They used a computer program to identify which proteins are only present in each stage and came up with hundreds of unique proteins for each stage.