ALSA-funded collaborative study demonstrates that enterovirus genetic sequences could not be detected in spinal cord from ALS patients

May 7, 2004

This study published in the April 27, 2004, edition of Neurology was initiated and funded by the ALSA-initiated research program led by Dr. Tom Maniatis, who chairs ALSA’s Lou Gehrig Challenge committee. The committee recognized the importance of determining whether there is an association between ALS and enteroviruses because reports in the literature were contradictory. To carry out the study, the committee approached the Centers for Disease Control and Prevention (CDC) and Dr. Martina Berger to participate in a double-blind study. Human samples were provided by Dr. Robert Brown from Massachusetts General Hospital and Dr. Benjamin Brooks of the University of Wisconsin, Madison, and control samples from mice were provided by Drs. Eugenia Dragunsky and Konstantin Chumakov from the U.S. Food and Drug Administration. Dr. Lucie Bruijn, Science Director and Vice President of The ALS Association, Dr. Tom Maniatis and Dr. Raymond Roos, University of Chicago, contributed to the study design, ensured that comparable techniques were established at the two centers and participated in the data analysis.

“This was an important collaborative effort involving ALSA, The University of California, Irvine and the CDC”, commented Dr. Bruijn. “The study results from UC, Irvine and the CDC failed to find evidence of an association of enterovirus infection with ALS in this sample set. Due to the challenges of maintaining a high sensitivity for this assay, a great deal of time was spent optimizing experimental conditions in order to further validate the strength of this study.”

The goal of this study was to test the association between ALS and enteroviruses by using a sensitive detection method. The samples consisted of 24 frozen spinal cord samples from ALS cases, 17 frozen spinal cord samples from non-ALS cases and 5 frozen spinal cord samples from positive controls. The positive controls were human spinal cord samples spiked with poliovirus and 2 poliovirus transgenic mice. These control samples were used to determine the sensitivity of the assays and standardize the analysis of the two study centers. There was no association between enteroviruses and ALS found in either of the centers.

Most ALS cases are sporadic and of unknown cause.  A viral infection has long been considered as a potential factor involved in the disease, in part because motor neurons are a target for certain viral infections. For example, poliovirus, which is an enterovirus, is known to infect motor neurons and can at times lead to a weakening condition called the post-polio syndrome years after paralytic poliomyelitis; however, there is no convincing evidence that poliovirus leads to ALS. Prior to this recent report, the data associating enteroviruses with ALS has been contradictory, and both negative and positive associations have been reported. In addition, there has been an anecdotal report that pleconaril, a compound that blocks and ameliorates the effect of enterovirus infections, showed benefit in an ALS patient.  The recent report in Neurology fails to support an association between enterovirus infection and ALS and provides no rationale for the treatment of this disease with anti-enteroviral drugs.

“In this study, a meticulous process validated the sensitivity and accuracy of enterovirus detection before the comparison of ALS and control samples,” said Dr. Brown.  “The results appear definitive.  This is an excellent model for an outside agency, such as The ALS Association, to play a neutral and supportive role in settling a key clinical question with important therapeutic implications.”

Questions and Answers:

1. Does this study mean that no virus is involved in the cause of ALS?

This study did not conclusively rule out an involvement of an enterovirus in ALS.  There are other viruses that this study did not measure that may potentially play a role in ALS.

2. Will more studies be done to determine the possible role of viruses and ALS?

Other groups are currently looking into whether retroviruses play a role.