Recent studies of phosphorylated neurofilament nf-h (pnf-h) as a biomarker of axonal injury and degeneration

           

Georgia World Congress Center: Room C305

Wednesday, Oct 18, 2006, 10:45 AM -11:00 AM

Authors:

           

*G. SHAW¹, S. B. LEWIS², R. WOLPER², M. WEISS³, K. ANDERSON⁴, C. YANG⁵, Y. WANG⁶, D. BORCHELT¹, D. HOWLAND^1,7;

 

¹Neuroscience, McKnight Brain Institute, Gainesville, FL, ²Neurosurgery, McKnight Brain Institute, Gainesville, FL, ³Division of Neonatology, University of Florida College of Medicine, Gainesville, FL, ⁴Department of Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, ⁵Neuroscience, McKnight Brain Institute, Gainesville, FL, ⁶ELISA, EnCor Biotechnology Inc., Alachua, FL, ⁷Neuroscience, Malcom Randall VA Med Center, Gainesville, FL.

 

We have recently described an ELISA allowing the sensitive detection of a promising biomarker of neuronal injury, the phosphorylated, axonal variants of the major neurofilament subunit NF-H (pNF-H; see Shaw et al. BBRC 336:1268-1277 2005). We showed that pNF-H is readily detectable in the blood of rodents with experimental CNS injuries, but not in the blood of uninjured animals. Here we describe more recent studies which show that informative levels of pNF-H can be reliably detected in the CSF and blood of a variety of animal models and humans with a range of damage and disease states. In particular we have performed a study of individuals prone to aneurysmal subarachnoid hemorrhage, with samples of blood and CSF taken every 6 hours over several days. The levels of pNF-H detected in the CSF of these patients are variable, and sudden sharp peaks in pNF-H expression appear to correlate well with the onset of vasospasm. We also detected pNF-H in the blood of some of these patients, generally those with a poorer outcome. In another study we showed that pNF-H can be readily detected in the blood of rodents transgenic for variants of human SOD1 which cause an ALS like pathology, but not in the blood of control mice or mice transgenic for unmutated human SOD1. Interestingly, pNF-H can be readily detected in the blood of G93A SOD1 mice well before symptoms of the ALS like disease state become apparent, a finding that has obvious diagnostic implications if it can be translated to humans. Finally, a directed search for other potential neuronal injury and degeneration biomarkers led to the discovery of several novel candidates, including ubiquitin C-terminal hydrolase 1 (UCHL1). UCHL1 is, like pNF-H, an abundant neuron specific protein which is released from damaged and degenerating neurons in large amounts, and can be readily detected with an appropriate ELISA. We will compare this biomarker with pNF-H in a variety of experimental and clinical contexts.

 

Disclosures:

           

G. Shaw, EnCor Biotechnology Inc., E. Ownership Interest (stock, stock options, patent or other intellectual property) ; S.B. Lewis, None; R. Wolper, None; M. Weiss, None; K. Anderson, None; C. Yang, None; Y. Wang, None; D. Borchelt, None; D. Howland, None.

Support:

           

NIH NS049134-01 project 3, NIH NS049134-01 project 3

           

EnCor Biotechnology Inc., EnCor Biotechnology Inc.

           

VA Medical Center, VA Medical Center