Evidence of Retrovirus in Blood of ALS Patients
March 2, 2005
[QUICK SUMMARY: Footprints of Retrovirus Found in ALS Patient Samples Leaves Researchers Unsure of Role of Retrovirus in the Disease]
Researchers reported in Neurology this month that blood samples collected from patients with amyotrophic lateral sclerosis (ALS) contain evidence of a retroviral enzyme more often than samples from controls without the disease. The genes for the enzyme, reverse transcriptase, could be carried silently in the human genome, or the virus might be associated with ALS. Much more work is required to settle the issue.
The findings reintroduce the notion that ALS, at least in some instances, could be linked to viral infection, a concept that has reappeared periodically when research focuses on the issue. Scientists have also considered viral infection for many other disorders of the nervous system from schizophrenia to multiple sclerosis, as well as ALS. A concrete link to viral infection has never been documented in any of these diseases.
In the February 8, 2005 issue of Neurology, British researchers including Ammar Al-Chalabi, Ph.D. at King's College, London; Jeremy Garson, M.D., Ph.D., at the University College, London; and U.S. collaborators including Robert Brown, Jr., M.D., D.Phil. and Merit Cudkowicz, M.D. at Massachusetts General Hospital, reported that blood serum from patients with ALS contained an enzyme of a retrovirus more often than did samples from controls who were not related to the patients. They found activity of the enzyme, reverse transcriptase, in 47 percent of serum samples drawn from 30 American ALS patients, and in 18 percent of 44 controls.
The scientists also found that 13 percent of samples collected from 16 patient spouses showed reverse transcriptase activity. Blood relatives of the ALS patients had about the same prevalence of the enzyme activity, at 43% of these 14 samples, as the patients themselves.
"The finding of a similarly increased prevalence in blood relatives of ALS patients raises the possibility that the observed (viral enzyme) activity might be due to an inherited endogenous retrovirus," the researchers wrote in their report.
If the presence of the enzyme activity reflected an actual viral infection, the marker would be expected to appear also in spouses, the researchers wrote, as retroviruses are readily passed in sexual intercourse.
The researchers noted that bits of retrovirus are common in all vertebrate genomes, and likely "represent the remnants of ancient ... infections by exogenous retroviruses." In mice, a specifically expressed retrovirus carried in the genome produces "an age-related motor neuron disease with a striking similarity to ALS in humans," they noted.
HIV can produce neurological symptoms in people. Historically, the polio virus's ability to infect and damage the nervous system led doctors to question whether a virus is involved in ALS. “Many different viral candidates have been proposed over the last three decades,” the researchers wrote, "but conclusive proof of a viral etiology has remained elusive."
“We typically explain to patients that the weight of evidence argues against a role for enteroviruses in ALS,” Brown commented. “A role for retroviruses is inconclusive thus far, but the (new) data clearly indicate that further research is warranted.”
The ALS Association (ALSA) has recognized the debate over a viral role in ALS, and funded a collaborative study between the Centers for Disease Control and several university centers that failed to confirm any link with enterovirus. Polio virus, an enterovirus, infects motor neurons and can at times lead to a weakening condition called the post-polio syndrome years after the initial infection. The report by the collaboration in the May 2004 edition of Neurology shows there is no rationale for the treatment of ALS with anti-enteroviral drugs.
In an accompanying editorial in the journal, Wim Robberecht of the University Hospital in Leuven, Belgium, and Burk Jubelt of SUNY Upstate Medical University in Syracuse, write that the enzyme activity found may be coming from an inherited retrovirus in the genome, but another factor is needed to cause disease as the blood relatives have similar prevalence of retrovirus, but do not have ALS. Or, the editorial writers suggest, the presence of reverse transcriptase activity “may be an epiphenomenon, linked to another (as yet unknown), pathogenically important factor.”
“These study results are interesting but should not encourage patients to seek antiviral treatment,” conclude Robberecht and Jubelt.
