Detection of serum reverse transcriptase activity in patients with ALS and unaffected blood relatives
Abstract
Background Retroviral involvement in the etiology of sporadic ALS has been suspected for several years since the recognition that both murine and human retroviruses can cause motor neuron disease-like syndromes. In a pilot study, an increased prevalence of a retroviral marker (reverse transcriptase [RT] activity) was demonstrated in the serum of British patients with ALS. The current investigation was designed to confirm and extend these findings in a geographically distinct patient cohort under blinded testing conditions. Methods A highly sensitive product-enhanced RT assay was employed to test coded sera obtained from 30 American patients with sporadic ALS and from 14 of their blood relatives, 16 of their spouses, and 28 nonrelated, nonspousal control subjects. Results Serum RT activity was detected in a higher proportion of ALS patients (47%) than in non-blood-related controls (18%; p = 0.008). The prevalence of RT activity in the serum of spousal controls (13%) was similar to that in other non-blood-related controls. Unexpectedly, the prevalence of serum RT activity in blood relatives of ALS patients (43%) approached that in the ALS patients themselves. Conclusions These results confirm that patients with ALS have a significantly higher prevalence of serum reverse transcriptase (RT) activity than that seen in unrelated control subjects. The finding of a similarly increased prevalence in blood relatives of ALS patients raises the possibility that the observed RT activity m…
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Earlier reports found relatively high levels of reverse transcriptase enzymatic activity in blood and cerebrospinal fluid from ALS subjects and blood relatives.
“earlier reports of relatively high levels of reverse transcriptase enzymatic activity in blood and cerebrospinal fluid from ALS subjects and blood relatives”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Steele et al. 2005
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“These results suggest that there may be an accumulation of LINE1 nucleic acids in TDPneg nuclei, consistent with the previously reported increase in reverse transcriptase activity in ALS (McCormick et al., 2008; Steele et al., 2005), which can potentially increase LINE1 DNA content even in the absence of complete retr…”
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- Authors
- Steele, A. J., Al-Chalabi, A., Ferrante, K., Cudkowicz, M. E., Brown, R. H., & Garson, J. A.
- Affiliations
- King's College London (GB)
- From the Centre of Virology (Drs. Steele and Garson), Department of Infection, University College London, and Department of Neurology (Dr. Al-Chalabi), Institute of Psychiatry, King’s College London, UK; and Department of Neurology (Drs. Cudkowicz and Brown, K. Ferrante), Massachusetts General Hospital, Boston, MA.
- Venue
- Neurology
- Published
- 2005-02-08
- Volume
- 64
- Issue
- 3
- Pages
- 454-458
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2008949845
- Cited by
- 112
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 8 · 2019: 9 · 2018: 14 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- amyotrophic lateral sclerosis, retroviral etiology, motor neuron disease, blood relatives, familial ALS, endogenous retroviruses
- MeSH terms
- Adult, Amyotrophic Lateral Sclerosis, Family, Female, Humans, Male, Middle Aged, RNA-Directed DNA Polymerase, RNA, Messenger, Sensitivity and Specificity, Cohort Studies, Single-Blind Method, Polymerase Chain Reaction, Age of Onset, DNA, Complementary, Spouses, Endogenous Retroviruses
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