Patients lack key lipids that fend off inflammation and nerve damage
By delving into the components of protective nerve coatings that get damaged in multiple sclerosis, scientists have identified a handful of lipid molecules that appear to be attacked by an immune system run amok.
Bolstering the supply of these lipids might help preserve these nerve coatings and, in the process, knock back the inflammation that contributes to their destruction, researchers report in the June 6 Science Translational Medicine.
In MS patients, rogue antibodies assault myelin, the fatty sheath that insulates nerves and facilitates signaling. Inflammation exacerbates the attack on myelin and the cells that make it. But other details of MS, including the roles of myelin lipids, have been less clearly understood.
“I think this is a very good study,” says Francisco Quintana, an immunologist at Harvard Medical School. “Overall, there are not many papers on lipids in MS. Technically, they are challenging and require a lot of expertise.”
To explore the role of lipids, the researchers studied spinal fluid from people with MS, healthy people and patients with other neurological disorders. Tests on the fluid showed that antibodies targeted four lipids more often in MS patients than in the other groups. Examination of autopsied brains from MS patients and people without MS revealed that, in the MS patients, these four lipids were depleted at the sites where the nerve coatings were damaged.
A nerve needs an intact myelin sheath to conduct signals. “It short-circuits if they are not there,” says study coauthor Lawrence Steinman, a neurologist at Stanford University. This nerve damage causes loss of muscle control and other symptoms characteristic of MS.
Steinman and his colleagues conducted tests in mice with a condition similar to MS and found that injections of the lipids over several weeks could limit severity of the disease and even reverse some symptoms in the animals. The four lipids — abbreviated as PGPC, azPC, azPC ester and POPS — share a similar phosphate group, to which the rogue antibodies bind.
Other tests in mice showed that side chains of fatty acids, attached to the lipids like fingers on a glove, “keep the myelin-making cells alive and reduce the inflammatory response,” Steinman says. “It turns out that the side chains are imbued with protective properties.” They repel inflammation and even kill the T cells that trigger it, the researchers found.
It could be that people with MS, who lack adequate supplies of these lipids and their protective fatty acids, fail to keep up with the destruction caused by antibodies and inflammation. But that dismal numbers game might present an opening for future research, Steinman says. Just as the mice benefited from receiving extra lipids, human patients might, too. And some tests now show that mice can take the lipids orally and still improve, he adds.
Quintana says that further animal studies will be needed to clarify the full effects of giving lipids to fight MS. “But it could potentially lead to some kind of therapy.”Joan Goverman, an immunologist at the University of Washington in Seattle, says the researchers deserve credit for their approach. “Looking at humans and then going back and incorporating that in animal models is a powerful way to understand the disease.”
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