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NEUROLOGY 2008;70:278-283
© 2008 American Academy of Neurology

Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate
A. L. McCormick, PhD, R. H. Brown, Jr, MD, DPhil, M. E. Cudkowicz, MD, MSc, A. Al-Chalabi, PhD, FRCP and J. A. Garson, MD, PhD
From the Centre for Virology, Department of Infection, University College London, London, UK (A.L.M., J.A.G.); Department of Neurology, Massachusetts General Hospital, Boston, MA (R.H.B., M.E.C.); Medical Research Council Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London, UK (A.A.-C.); and Department of Virology, University College London Hospitals National Health Service Foundation Trust, London, UK (J.A.G.).

Address correspondence and reprint requests to Dr. Jeremy A. Garson, University College London Centre for Virology, Windeyer Institute, 46, Cleveland St., London, W1T 4JF, UK j.garson@ucl.ac.uk

Background: Retroviral involvement in amyotrophic lateral sclerosis (ALS) has been suspected for several years since the recognition that both murine and human retroviruses can cause ALS-like syndromes. Nonquantitative studies have demonstrated the retroviral enzyme reverse transcriptase (RT) in ALS patients' sera, but the amount and source of RT activity are unknown. We therefore developed a quantitative assay to study RT levels in ALS and examined the possibility that the recently discovered human gammaretrovirus XMRV (xenotropic MuLV–related virus) might be the source of the RT activity.

Methods: A quantitative product-enhanced RT assay was used to measure RT activity levels in serum and CSF. XMRV sequences were sought by PCR analysis of DNA and RNA extracted from blood.

Results: Fifty percent of ALS patients' sera contained >6 x 10–8 RT units/mL as opposed to 7% of control sera (p = 0.008). The levels of RT activity in ALS patients were comparable to the levels observed in patients infected with HIV. RT activity was detected in only 1 of 25 CSF samples tested. XMRV sequences were not found in any of 25 nucleic acid extracts obtained from ALS patients' blood.

Conclusions: These findings further support the concept of retroviral involvement in amyotrophic lateral sclerosis (ALS) and demonstrate that serum is more suitable than CSF for assay of reverse transcriptase (RT) activity in this disease. The levels of serum RT activity detected are comparable to those found in HIV infection. XMRV is not detectable in the blood of ALS patients, and the agent responsible for ALS-associated RT activity therefore remains unidentified.


Abbreviations: ALS = amyotrophic lateral sclerosis; BMV = brome mosaic virus; cDNA = complementary DNA; HTLV = human T-lymphotropic virus; MuLV = murine leukemia virus; PERT = product-enhanced reverse transcriptase; qPERT = quantitative real-time product-enhanced reverse transcriptase; rec-MMuLV-RT = recombinant Moloney murine leukemia virus reverse transcriptase; RT = reverse transcriptase; XMRV = xenotropic MuLV–related virus.


http://www.neurology.org/cgi/content/short/70/4/278
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Supplemental data at www.neurology.org

Supported by Project ALS (New York).