PEPTIDE MIGHT IMPROVE MANAGEMENT OF MULTIPLE SCLEROSIS
COLUMBUS, Ohio -- New research shows that feeding rats a peptide found in guinea pigs prevents the rats from developing a disease that is similar to multiple sclerosis in humans.
The finding has important implications for the design of clinical trials testing dietary supplements that might slow the progression of multiple sclerosis.
The study was led by Caroline Whitacre, professor and chairperson of medical microbiology and immunology, and Najma Javed, postdoctoral fellow, both at Ohio State University.
The results revealed that a tiny change in a protein can have a giant effect on whether a peptide will or won't induce oral tolerance.
Oral tolerance involves the use of a dietary supplement to train the immune system to stop attacking -- to tolerate or accept -- a protein found naturally in the body. The
destruction of natural proteins by immune cells causes autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, diabetes, thyroiditis, and myasthenia gravis.
The study examined whether feeding a fragment of a protein -- a peptide -- to rats would prevent the animals from developing experimental autoimmune encephalomyelitis (EAE), an autoimmune disease similar to multiple sclerosis.
The research found that a difference in one amino acid of the 20 that made up the peptide determined whether or not the protein prevented the disease in the animals.
"The results were really dramatic," said Whitacre. "Changing that one amino acid made a huge difference in disease outcome."
The work was presented at the 14th Annual Peptide Symposium held at Ohio State University in June.
"If we know which protein in the body is being attacked in an autoimmune disease, we can sometimes add that protein to the person's diet and turn down, or even turn off, the immune system's reaction to it," said Whitacre. This can alleviate or reduce the effects of the disease.
In both EAE and multiple sclerosis, immune cells attack the myelin sheath surrounding nerves in the brain and spinal cord. This leads to the weakness, loss of coordination, and other neurological problems that characterize the diseases.
Preliminary clinical trials reported in 1993 suggested that myelin taken in capsule form might slow progression of multiple sclerosis.
And, in an earlier study, Whitacre and a group of colleagues tested that idea in rats. They found that if myelin basic protein obtained from guinea pigs was fed to the rats before they develop EAE, the disease did not develop in most of the animals. On the other hand, if the rats were fed myelin basic protein from rats, the disease did develop.
"This shows that oral tolerance and oral administration of proteins that are affecting the immune system are both very immunologically specific," said Whitacre. "Changing the structure of the protein by one amino acid can make the difference between preventing the disease and permitting the disease."
These results were remarkable because the structure of myelin basic protein from guinea pigs is nearly identical to that from rats -- they differ by only one of 170 amino acids.
The present study tested whether a peptide of myelin basic protein would produce the same results when fed to the animals.
A peptide would be better for patients to take because individual peptides are easier to produce in pure form than the entire protein.
How might adding myelin basic protein to their diet help people with multiple sclerosis?
"Most MS patients have remitting-relapsing phases of the disease," said Whitacre. "We would give patients this kind of therapy while they're in remission in an attempt to forestall further progression of the disease."
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Contact: Caroline Whitacre, (614) 292-5889
Written by Darrell E. Ward, (614) 292-8456