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.
Project A.L.S., a 501©3 that is committed to finding and funding treatments and a cure, began supporting this study in 2001 after learning that Drs. Garson and Al-Chalabi, who led the intriguing original investigation, had run out of funding. "This was a dormant study, a forgotten study, which Project A.L.S. discovered in a simple literature search on the internet," said Valerie Estess, director of research for Project A.L.S. "I am pleased that Project A.L.S. was able to give this work a second life, and that it is yielding solid clues as to the possible causes of ALS."
Journal
Neurology