• Clarke, Lorne


    Investigator, BC Children's Hospital
    Professor, Department of Medical Genetics, University of British Columbia

    Degrees / Designations
    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Lab Phone
    Mailing Address

    BC Children's Hospital
    Room C234
    4500 Oak Street
    Vancouver, BC V6H 3N1

    Affiliate Websites
    Research Areas
    • Lysosomal storage disease
    • Inborn errors of metabolism
    • Genetic therapies

    The main focus of my work is the investigation of the complex series of events at the cellular and tissue level that are at play in the evolution and of genetic disease. It is hoped that an understanding of disease at this level will result in the development of specific forms of therapy for rare genetic disease. My group has chosen to focus on a series of devastating progressive disorders termed lysosomal storage diseases.

    Current Projects

    Clinical trial of recombinant iduronidase in the treatment of MPSI
    Clinical trial of recombinant iduronidase in the treatment of MPSI. This is a complex multicenter multinational clinical trial of the use of iduronidase for the treatment of the genetic disease MPS I.

    Proteomic approach to the identification of biomarkers of MPS disease
    This project involves the identification, through serum proteomic studies, markers of disease severity and responsiveness. Markers will initially be identified in a murine model and subsequently validated in human samples.

    Clinical trial of BH4 for the treatment of classical PKU 
    It has now been suggested that small molecules can act as chemical chaperones for misfolded proteins that are caused by point mutations of genes. PKU is an inborn error of metabolism that is currently treated by very restrictive diet. In vitro studies have shown that BH4 can stabilize mutant PAH enzyme and lead to greater tolerance of PHE in the diet.

    Selected Publications

    Muenzer J, Wraith JE, Clarke LA; International Consensus Panel on Management and Treatment of Mucopolysaccharidosis I.: Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009 Jan;123(1):19-29.

    Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Sidman M, Kakkis ED, Cox GF.: Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis. Pediatrics. 2009 Jan;123(1):229-40.

    Feillet F, Clarke L, Meli C, Lipson M, Morris AA, Harmatz P, Mould DR, Green B, Dorenbaum A, Giovannini M, Foehr E; Sapropterin Research Group.: Pharmacokinetics of sapropterin in patients with phenylketonuria. Clin Pharmacokinet. 2008 Dec; 47(12):817-25.

    Tyson C, Qiao Y, Harvard C, Liu X, Arbour L, Bernier FP, McGillivray B, Farrell SA, Chudley AE, Clarke L, Gibson W, Dyack S, McLeod R, Costa T, Van Allen MI, Yong S-L, Graham GE, MacLeod P, Patel MS, Hurlburt J, Holden JJA, Lewis SME, Rajcan-Separovic E.: Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH. Molecular Cytogenetics. 2008 Nov 11;1:23.

    Randall DR, Colobong KE, Hemmelgarn H, Sinclair GB, Hetty E, Thomas A, Bodamer OA, Volkmar B, Fernhoff PM, Casey R, Chan AK, Mitchell G, Stockler S, Melancon S, Rupar T, Clarke LA.: Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Mol Genet Metab. 2008 August;94(4):456-61.

    Rempel, B.P., Clarke, L.A. , Withers, S.G. A homology model for human alpha-L-iduronidase: insights into human disease. Molecular Genetics and Metabolism, 2005, available online February 2005.

    James E. Wraith, Lorne A. Clarke, Michael Beck, Edwin H. Kolodny, Gregory M. Pastores, Joseph Muenzer, David Rapoport, Kenneth Berger, Stuart Swiedler, Emil Kakkis, Tanja Braakman, Elenie Chadbourne, Karen Walton-Bowen, Gerald Cox. Enzyme replacement therapy for Mucopolysaccharidosis I: A randomized, double-blind, placebo-controlled, multinational study of recombinant human a-L-iduronidase (Laronidase). Journal of Pediatrics, 144(5):581-8, May 2004.

    Vallance, H., Chaba, T., Clarke, L.A. , Taylor , G. Pseudo-lysosomal storage disease caused by EMLA cream.Journal of Inherited Metabolic Dis., 27(4):507-11, 2004.

    Nieman, C.E., Wong, A.W., He, S., Clarke, L.A., Hopwood, J. J., Withers, S. Family 39 a-L-iduronidases and B-D-Xylosidases react through similar glycosylenzyme intermediates: Identification of the human iduronidase nucelophile. Biochemistry, 42, 8054 - 8065, 2003.

    Gillet, P.M., Scheiber, R.A., Jevon, G.P/, Israel , D.M., Warshawski, T., Vallance, H., Clarke, L.

    Mucopolysaccharidosis type VII (Sly syndrome) presenting as neonatal cholestasis with hepatomegaly. J Ped Gastro Nutri. 33, 216-220., 2001.

    Russell, C., Hendson, G., Jevon, G., Matlock, T., Yu, J., Aklujkar, M., Ng, K-Y, and Clarke, L.A. Murine MPS I: Insights into the Pathogenesis of Hurler Syndrome. Clinical Genetics Vol. 53, 349-361, 1998. Russell, C.S., Clarke, L.A. Recombinant proteins for genetic disease. Clin. Genet. 25 t. 55:389-394, 1999.

    Clarke L.A., Russell, C.S., Pownall, S., Warrington , C.L., Borowski, A., Dimmick, J.E., Toone, J., Jirik, F.R. Murine Mucopolysaccharidosis Type I: Targeted disruption of the Murine a-L-iduronidase gene. Human Molecular Genetics 4503-511, 1997.

    Honours & Awards

    Canadian Glyconomics network Award- 2017

    Canadian Organization for Rare Disorders (CORD) Rarity Award for Scientific Excellence - 2013. 

    Canadian Society for Clinical Investigation Schering Research Award ($25,000/year) – 1993-1995

    B.C. Children’s Hospital Research Foundation Fellowship – 1992-1993

    Research Group Members

    • Dr. Elly Hetty – Clinical study coordinator
    • Karin Yip – Chief technician
    • Graham Sinclair – Postdoctoral fellow
    • Derrick Randall – Graduate student