Advisory Board

Dr. Sarah J. Tabrizi

The Scientific American article New Targets for Treating Huntington’s Disease Discovered said

Researchers have discovered early blood markers in people genetically predisposed to develop Huntington’s disease, a mysterious neurodegenerative disorder. These signs may provide future targets for staving off or even preventing symptoms from developing.
 
“In gene carriers, before they show signs of the disease, the neurodegeneration process has already started,” says Sarah Tabrizi, a neurologist at University College London and coauthor of the study, which appears in The Journal of Experimental Medicine. “This indicates that the process of neuronal dysfunction which goes on to neuronal degeneration is theoretically rescuable.”
 
Tabrizi and her team collected blood samples from 194 people with the gene to determine whether there were early markers that could be targeted to delay the disease’s onset. They found that they all produced an excess of cytokines (immune system scouts that signal other disease-fighting cells to combat invading germs or to fix damaged tissue) — some as early as 16 years before researchers would have expected symptoms to appear.

Sarah J. Tabrizi, MD FRCP PhD is Reader in Neurology and Neurogenetics, Institute of Neurology, MRC Prion Unit, University College London and is Fellow of the Royal College of Physicians.
 
After studying Biochemistry and Medicine at Edinburgh University, Sarah trained in Neurology at the Royal Free Hospital and the National Hospital for Neurology and Neurosurgery. She undertook her PhD as an MRC Clinical Training Fellow studying the role of mitochondria in mechanisms of cellular neurodegeneration with Tony Schapira at UCL. In 2002 she was awarded a 5-year National Clinician Scientist Fellowship, which has enabled her to establish her own laboratory research group, studying basic cellular mechanisms of neurodegeneration, concentrating on protein misfolding diseases, particularly prion disease and Huntington’s disease.
 
Her prion lab group works closely with John Collinge and the MRC Prion Unit and is interested in the cell biology of prions. Prion diseases, such as BSE in cattle and variant CJD (vCJD) in humans, are rare but deadly diseases of the brain. In these diseases, normal prion protein in our cells becomes abnormally shaped and forms toxic prions. These prions start to accumulate in the brain, and cause previously healthy brain cells to die. However, the exact mechanism by which this abnormal prion protein kills cells is not known.
 
Sarah’s work suggests that a problem with the ubiquitin-proteasome system (UPS) might be involved. The UPS is a type of cellular recycling machinery that breaks up damaged proteins into small units and helps dispose of them. This protects the cells from a potentially toxic build-up of faulty proteins inside the cell. Her group is working on studying this cellular garbage disposal system to help her understand how prions cause brain cells to die. Some of her work was recently summarized in an article in The Economist.
 
She also leads a large research program in Huntington’s disease, focusing on the search for biomarkers of disease progression and disease pathogenesis to power therapeutic trials. She is PI of TRACK-HD, a major international research initiative aimed at understanding the biology of the degenerative changes in premanifest and early stage HD gene carriers, both in the central nervous system and peripherally.
 
Sarah coauthored Expression of mutant {alpha}-synuclein causes increased susceptibility to dopamine toxicity, Disease-related Prion Protein Forms Aggresomes in Neuronal Cells Leading to Caspase Activation and Apoptosis, Prion diseases, Gene expression in Huntington’s disease skeletal muscle: a potential biomarker, Disease-Associated Prion Protein Oligomers Inhibit the 26S Proteasome, Somatic and germline mosaicism in sporadic early-onset Alzheimer’s disease, Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6/2 transgenic mouse model of Huntington’s disease, Learning and Recall in Subjects at Genetic Risk for Alzheimer’s Disease, and Hsp27 overexpression in the R6/2 mouse model of Huntington’s disease: chronic neurodegeneration does not induce Hsp27 activation.
 
Read Prions Block Cell Recycling System To Cause Disease.