s Hopkins Researchers Discover Key Protein Linked To TM & MS

[Guest guest]

s Hopkins researchers discover key protein linked to transverse

myelitis and multiple sclerosis

Hopkins researchers have discovered a single molecule that is a cause

of an autoimmune disease in the central nervous system, called

transverse myelitis , that is related to multiple sclerosis.

In a study published in the October issue of The Journal of Clinical

Investigation, psychiatrist Adam Kaplin, M.D., Ph.D., an assistant

professor at The s Hopkins University School of Medicine, and

neurologist Kerr, M.D., Ph.D., also an assistant professor at

Hopkins, showed that the levels of the protein, IL-6, are

dramatically elevated in the spinal fluid of transverse myelitis

patients.

Although the majority of TM patients suffer a single attack, 15

percent to 30 percent of patients go on to develop full-blown MS. TM

evolves rapidly and without warning and usually results in permanent

impairment, including weakness of the legs and arms, bowel and

bladder dysfunction, pain and paralysis.

IL-6 is a chemical messenger that cells of the immune system use to

communicate with one another. One of the cell types injured by high

levels of IL-6 includes oligodendrocytes, which help produce the

protective myelin sheath coating around nerve cells. The findings

offer one possible mechanism responsible for demyelinating disorders,

such as TM and MS, and may aid in the development of effective

therapies against these disorders, the researchers say.

" This is the first time a single culprit has been identified as

causing a CNS autoimmune disease, " said Kaplin.

The researchers began investigating the protein IL-6 when they became

aware that TM patients suffered from memory impairment and

depression. IL-6 has been implicated in mood and concentration

disorders.

" This discovery is a success story that begins with listening

carefully to what patients are telling us about their suffering and

then collaborating across disciplines to open up new avenues of

investigation, " said Kaplin.

" TM is related to other autoimmune disorders of the nervous system,

including Guillain-Barré syndrome, MS and acute disseminated

encephalomyelitis. This study may give us a foothold in understanding

all of these disorders and how they are linked together. The benefit

is, therefore, not only to those who are paralyzed by TM, but to

those who have disabilities due to a variety of autoimmune disorders.

We are actively using these findings to aid in developing future

diagnostic, prognostic and therapeutic advancements, " said Kerr,

director of the s Hopkins Transverse Myelitis Center, the only

center devoted to TM in the world.

Researchers analyzed 42 inflammatory proteins in the cerebrospinal

fluid of both TM and healthy patients. They found that IL-6 was

consistently elevated in TM patients' spinal fluid. Further, the

level of IL-6 directly correlated with the severity of paralysis.

Using cell culture and animal studies, the researchers confirmed that

elevated IL-6 levels were directly injurious to the spinal cord. They

showed that spinal fluid from TM patients induced death of spinal

cord cells when cultured in a dish and that IL-6, when infused in

adult rats, induced paralysis. Under the microscope, tissue from IL-6-

infused rats showed demyelination and injury of axons, pathology that

was nearly identical to that seen in human patients with TM.

Kerr and Kaplin also deduced that the reason IL-6 elevations injure

only the spinal cord and not other regions of the nervous system was

because distinct regions of the nervous system have different

responses to IL-6. They concluded that these different types of

responses might be a part of why different autoimmune disorders of

the nervous system affect distinct regions and cause distinct

symptoms.

" When we started, we knew nothing about the bad players in this drama

in the spinal cord of CNS autoimmune diseases - it was a classic

murder mystery and we set out together to find out 'who done it', "

said Kaplin. " We've answered who could have done it, and how, and

where. "

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Funding for this study was provided by the National Institutes of

Health.

Other investigators involved in this study, conducted solely at

Hopkins, were Deepa M. Deshpande, M.S.; k , B.S.; Chitra

Krishnan, M.S.; S. Carmen, B.S.; Irina Shats, M.S.; Tara

ez, B.S.; Drummond, B.S.; Sonny Dike, M.D.; Mickail

Pletnikov, M.D., Ph.D.; Sanjay C. Keswani, M.B.; H. Moran,

Ph.D.; A. Pardo, M.D., and A. Calabresi, M.D.