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New evidence of retroviral involvement in amyotrophic lateral sclerosis


Project A.L.S. funds breakthrough research

A significant proportion of patients suffering from ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease or motor neuron disease, have a marker of retrovirus activity in their blood, reports the February 8 issue of the medical journal Neurology. The study was led by Dr. Jeremy A. Garson of University College London, UK and Dr. Ammar Al-Chalabi of King’s College London, UK, and was funded in full by Project A.L.S.

The research confirms and extends the results of earlier work by Drs Garson and Al-Chalabi in which they had found evidence of retroviral involvement in a group of UK patients with ALS. The present study on Americans with ALS, done in collaboration with Drs. Robert H. Brown, Jr. and Merit Cudkowicz at the Massachusetts General Hospital/Harvard Medical School, shows that 47% of ALS patients have reverse transcriptase activity detectable in their serum.

"This is a very exciting finding that points towards the possibility of retrovirus involvement in ALS. However, much work remains to be done and we are very much aware that in virology, as in other branches of medical science, finding an association is not the same as proving a cause," said Dr. Garson.

Reverse transcriptase is an enzyme associated with retroviruses. The presence of this enzyme activity in serum therefore implies that a retrovirus may be involved in ALS. It is not yet known whether the enzyme activity detected in this study reflects activation of a so-called endogenous retrovirus, which is already present in human DNA, or infection with an external exogenous retrovirus.

Retroviruses have been known for many years to be implicated in the pathogenesis of ALS-like syndromes in certain strains of mice and in rare cases of individuals with HIV infection. Drs. Garson and Al-Chalabi have demonstrated that the previously described human retroviruses HIV and HTLV are not involved in typical ALS cases. Future work will determine whether an endogenous retrovirus is activated in ALS, or whether there is infection with a novel, exogenous ALS-associated retrovirus.

The next phase of this exciting work, funded by Project A.L.S., has recently commenced. It is hoped that further progress in this area will lead to the development of improved diagnostic tests and novel therapeutic strategies, and to a greater understanding of the fundamental causes of this progressive and ultimately fatal neurological disease.

"The important study from King’s College and University College gives new life to the hypothesis that ALS is a consequence of an atypical infection; follow-up studies will now be essential to pin down the actual offending agent," said Dr. Brown.

Valerie Estess | EurekAlert!
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