A protein found primarily in the lens of the eye could be the critical “tipping point” in the spiral of inflammation and damage that occurs in multiple sclerosis, researchers at the Stanford University School of Medicine report.
This protein – alphaB-crystallin – is not normally found in the brain, but develops in response to the injuries inflicted on nerve cells by multiple sclerosis. The nerve-cell injuries can cause people to suffer loss of motor control and even paralysis.
“The big breakthrough in this paper is answering the question ‘What is alphaB-crystallin doing”‘” said Lawrence Steinman, MD, professor of neurology and neurological sciences. Steinman and his team demonstrated that the protein plays a protective role in a mouse model of multiple sclerosis – and when injected in mice, it can reverse paralysis. Their findings will be published in the June 13 advance online edition of Nature.
In multiple sclerosis, the immune system launches an attack against the myelin sheath surrounding nerve cells, causing them to misfire. According to the Multiple Sclerosis Foundation, up to 500,000 people in the United States have been diagnosed with the condition, which causes varying symptoms depending on the location and extent of the scarring of the myelin sheath. Common symptoms include fatigue, weakness, vertigo, numbness and vision problems.
For reasons not yet understood, the immune system considers the expression of the alphaB-crystallin protein in the brain a danger signal and attacks this healing substance. “Like a runaway truck careening down a mountain and then having the brakes fall off, the immune attack against alphaB-crystallin worsens the situation,” said Steinman. And remarkably, he noted, addition of that protein works like restoring the failing brakes, returning control.
If the same recovery is seen in humans, the protein might someday be used to treat multiple sclerosis. “It is a real delight to see that the same material that is naturally produced, that has these protective effects, could potentially be harnessed and used as a therapeutic itself,” said Steinman.
The team is optimistic about the protein being used as a therapy, but Steinman and Shalina Ousman, PhD, a postdoctoral researcher in his laboratory and the first author of the publication, emphasized that it is still a long way from being tested in humans.
The recognition of this protein’s role in multiple sclerosis began more than a decade ago, when Dutch researcher Johannes Van Noort, PhD, found that the main stimulant of the immune system’s attack on the brain was not the presumed culprit of one of the parts of myelin, but alphaB-crystallin, the major structural protein of the lens of the eye.
“For some reason, the protein gets turned on in the brain where it’s not expected to be,” said Steinman, who wrote an editorial about Van Noort’s finding in 1995 when it was published in Nature. Since then, Steinman and others in the field wondered what it means that a protein normally found in the lens of the eye suddenly appears in the brain. In 2001, Steinman published work in Science cataloging the proteins most abundant in multiple sclerosis, and found that alphaB-crystallin ranked first.