As with many neurodegenerative diseases, viruses have waxed and waned in popularity as possible causative agents in amyotrophic lateral sclerosis (ALS, known as Lou Gehrig’s disease in the U.S.). A study in this month’s issue of Neurology, which finds RNA fragments of an enterovirus in spinal tissue of deceased ALS patients, may revive the viral theory in this disease.
Viruses are especially attractive causative candidates for ALS, write George Karpati of the Montreal Neurological Institute and Marinos Dalakas of NINDS in an editorial in the same issue, because the symptoms and pathology of the disease have a number of similarities to polio, which is caused by the poliovirus, the prototypical enterovirus. Yet efforts to isolate viruses from CSF and other nervous system components, or to transmit the disease experimentally with these substances, have failed to show a clear viral association with ALS.
Martina Berger (now at the University of California-Irvine), Bruno Lina, and their colleagues in Lyon, France, now armed with new, and more sensitive, variations on polymerase chain reaction (PCR) show that 15 of 17 ALS patients in their study had specific enteroviral RNA sequences in neural tissue from formalin-fixed spinal cord tissue, compared to only one of 29 control subjects (with miscellaneous neurologic diseases). When they sequenced the enteroviral RNA, they found that it had a high degree of homology with echovirus serotype 7, an enterovirus that usually avoids brain and spinal cord tissues.
Enteroviruses are ubiquitous in humans and the authors are careful to say that their results could simply mean that motor neurons damaged by some other mechanism in ALS might be more susceptible to infection by a ubiquitous virus. But the other intriguing possibility is that the virus has a causal role. It may have escaped detection until now because it remains dormant within neuronal nuclei for long periods (viral latency), or replicates at such low levels that it is not detected by the immune system (persistent infection).-Hakon Heimer.
Reference:Berger MM, Kopp N, Vital C, Redl B, Aymard M, Lina B. Detection and cellular localization of enterovirus RNA sequences in spinal cord of patients with ALS. Neurology 2000 Jan;54:20-25. Abstract
Karpati G, Dalakas MC. Viral hide-and-seek in sporadic ALS: a new challenge. Neurology 2000 Jan 11;54:6-7. Abstract
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