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More MS news articles for May 2003

More Evidence Points to Direct Involvement of HHV-6 in MS Pathogenesis

May 09, 2033
By Karla Gale
Reuters Health
New York

Powerful molecular techniques used to evaluate brain tissue at different stages in the development of multiple sclerosis (MS) support the theory that human herpesvirus 6 (HHV-6) is present in MS lesions and may be actively involved in disease pathology, according to two reports in the Journal of Infectious Diseases for May 1.

The first study established that HHV-6 DNA is present at high frequencies in glial cells of acute-phase lesions in patients with MS. In the second report, HHV-6 was significantly more common in MS plaques than in normal-appearing white matter of patients with long-standing MS, healthy control subjects, or brains individuals with other neurologic diseases.

The results are so powerful that the two research groups are now in the planning stages of a clinical trial to test the efficacy of antiviral agents for treatment of MS.

Dr. Andrew D. Goodman and colleagues at the University of Rochester School of Medicine and Dentistry, New York, obtained biopsy specimens of lesions that presented as cerebral tumors in 5 patients subsequently diagnosed with MS. None had received immunomodulatory therapy at the time of biopsy.

A sensitive in situ polymerase chain reaction (ISPCR) method recently developed by Dr. Goodman's group revealed HHV-6 DNA in oligodendrocytes, lymphocytes and microglia in all five lesions.

"In our study, viral DNA does locate to oligodendrocytes, the cells that make the myelin that is the target of inflammation," Dr. Goodman told Reuters Health. "The implication is that this could be the target of the immune response that causes inflammation and ultimately scars the nervous system."

What is unique about the University of Rochester study, he added, is that the findings "couldn't have been impacted by treatment or years of chronic illness."

Dr. Goodman cautioned that his group's study "does not provide evidence of direct active infection" because they only found latent virus, and his group has yet to test tissue for the presence of other viral agents. "But other groups have previously reported active infection," he added, and his laboratory is close to developing ISPCR tests for additional herpes and non-herpes viruses.

Meanwhile, Dr. Steven Jacobson and colleagues, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, examined the frequency of HHV-6 DNA in brain tissue samples from MS patients, both MS plaques and normal-appearing white matter (NAWM), as well as from patients with non-MS brain disorders and from healthy control subjects.

They obtained 64 samples from 30 MS plaques of 13 patients with MS, as well as 44 samples of NAWM from 10 of the same patients. Thirty-seven (75.8%) MS plaques and seven (15.9%) NAWM samples were positive for HHV-6 specific DNA sequences, a significant difference (p < 0.0005).

"The NAWM specimens...were dissected in close proximity to lesion areas, suggesting that HHV-6 positivity is associated with MS lesions in particular, rather than with brain regions where lesions are common," writes the NIH research group.

The frequency in MS plaques was also significantly higher than in samples from 12 pathologically normal brains (26.8%; p > 0.0170) and in 13 patients with other neurologic diseases (21.7%; p > 0.003).

Results of both studies suggest that "the increased presence of HHV-6 DNA may not be reflective of a generalized reactivation that may occur during neuroinflammation," Dr. Jacobson and his colleagues note.

In an interview with Reuters Health, Dr. Jacobson remarked that genital and oral herpes virus infections are known to cycle through quiescent and reactivated states. He postulated, "Could a similar process be occurring in MS?"

Positive results from clinical trials testing antiviral drugs would provide supportive evidence that HHV-6 is actively involved in the disease process, he said. "But there are a lot of nitty-gritty details to be worked out" before clinical trials can be conducted, such as type of patients to include and how to monitor clinical efficacy, including reduction in MRI lesion load, disease course, or reduction and viral load.

J Infect Dis 2003;187:1365-1387.

Copyright © 2003 Reuters Ltd