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Elevated serum angiogenin levels in ALS

From the Department of Physiology (S.C., D.K., J.H.M.P.), Royal College of Surgeons in Ireland; Department of Neurology (S.C., O.H.), Beaumont Hospital; National Centre for Medical Genetics (M.J.G., S.E., A.G.), Our Lady's Hospital for Sick Children; and Department of Clinical Neurological Sciences (S.C., M.J.G., O.H.), Royal College of Surgeons in Ireland, Dublin, Ireland.

Address correspondence and reprint requests to Dr. Simon Cronin, The Irish ALS Research Group, Neurology Department, Beaumont Hospital, Dublin 9, Ireland; e-mail: scronin{at}rcsi.ie

Background: The role of hypoxia responsive genes in the pathogenesis of ALS was first suggested when deletions of the hypoxia-responsive element of vascular endothelial growth factor (VEGF) promoter caused a motor neuron disease phenotype in mice. The discovery of ALS-associated mutations in ANG, a hypoxia responsive gene coding for the protein angiogenin, has further supported this pathogenic mechanism in human ALS. In endothelium, angiogenin can regulate expression of VEGF. To date, the patterns of serum angiogenin expression among patients with ALS have not been assessed.

Methods: Serum angiogenin and VEGF levels were quantified at diagnosis in 79 patients with definite or probable ALS and 72 healthy controls, using a quantitative sandwich enzyme-linked immunoassay.

Results: Patients with ALS exhibited higher serum angiogenin (p = 0.006) but not VEGF (p = 0.55) levels than matched control subjects. Subgroup analysis showed a greater elevation in angiogenin levels for spinal- (p < 0.001) than bulbar- (p = 0.11) onset ALS vs controls. At 12 months, angiogenin levels remained elevated. No correlation was noted between angiogenin and VEGF levels (r = –0.08, p = 0.49) in ALS patient serum.

Conclusion: These data suggest a modest elevation in serum angiogenin in ALS at diagnosis. Further investigation will be required to assess the utility of serum angiogenin as a biomarker for ALS and as a predictor of disease progression.

Supported by a translational research grant from the Charitable Infirmary Charitable Trust (S.C.) and by the Health Research Board of Ireland (M.G., O.H.).

Disclosure: Royal College of Surgeons in Ireland hold a patent on angiogenin for therapeutic uses in ALS. The College asserts its rights over this patent and all proceeds generated thereof for its charitable aims (Registered Charity No. CHY 127). The authors M.J.G. and O.H. are listed as inventors on this patent.

Received May 31, 2006. Accepted in final form July 28, 2006.

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				D. Irwin, C. F. Lippa, and J.M. Swearer Cognition and Amyotrophic Lateral Sclerosis (ALS) American Journal of Alzheimer's Disease and Other Dementias, September 1, 2007; 22(4): 300 - 312. [Abstract] [PDF]