Judith C.T. van Deutekom, PhD
Dr.
Judith C.T. van Deutekom was project leader of the DMD Genetic Therapy Group, and
as research staff member (UHD) employed by the Department of Human Genetics of
the Leiden University Medical Center (LUMC) until February 2007. As a molecular biologist she has an
extensive track record in the genetic research of muscular dystrophies since
1991, and is dedicated to the development of a genetic therapy for Duchenne
Muscular Dystrophy (DMD) since her postdoctoral studies at the University of
Leiden (The Netherlands) and the University of Pittsburgh Medical Center
(Pennsylvania, USA). She has been awarded for her research on antisense
oligoribonucleotides as small molecule drugs for DMD by the Princess
Beatrix fund in 2001 and by the LUMC (C.J. Kok Award) in 2003.
She is currently working as Head of Research for Prosensa B.V., where one of
her tasks is to make the antisense therapy clinically applicable for DMD.
Publication List
van Deutekom, J.C.T., Wijmenga, C., van Tienhoven, E.A.E., Gruter, A‑M., Hewitt, J.E., Padberg, G.W., van Ommen, G‑J.B., Hofker, M.H., Frants, R.R. (1993) FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum. Mol. Genet., 2, 2037‑2042.
Bruyn, R.P.M., Van Deutekom, J.C.T., Frants, R.R., Padberg, G.W. (1993) Hereditary spastic paraparesis: Clinical and genetic data from a large Dutch family. Clinical Neurology and Neurosurgery, 95, 125‑129.
Wijmenga, C., Frants, R.R., Hewitt, J.E., van Deutekom, J.C.T., van Geel, M., Wright, T.J., Padberg, G.W., Hofker, M.H., van Ommen, G-J. (1993) Molecular genetics of facioscapulohumeral muscular dystrophy. Neuromuscular Disorder, 3, 487-491.
Van Deutekom, J.C.T, Bruyn, R.P.M., Van den Boorn, N., Sandkuijl, L.A., Padberg, G.W., Frants, R.R. (1994) Pure hereditary spastic paraparesis: An exclusion map covering more than 40% of the autosomal genome. Hum Genet, 93, 408‑414.
Hewitt, J.E., Lyle, R., Clark, L.N., Valleley, E.M., Wright, T.J., Wijmenga, C., Van Deutekom, J.C.T., Francis, F., Sharpe, P.T., Hofker, M., Frants, R.R., Williamson, R. (1994) Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum Mol Genet, 3, 1287‑1295.
Wijmenga, C., van Deutekom, J.C.T., Hewitt, J.E., Padberg, G.W., van Ommen, G‑J.B., Hofker, M.H., Frants, R.R. (1994) Pulsed field gel electrophoresis of the D4F104S1 locus reveals the size and parental origin of the FSHD associated deletions. Genomics, 19, 21‑26.
Frijns, C.J., Van Deutekom, J., Frants, R.R., Jennekens, F.G. (1994) Dominant congenital benign spinal muscular atrophy. Muscle Nerve, 17,192-197.
Hazan, J., Fontaine, B., Bruyn, R.P., Lamy, C., van Deutekom, J.C., Rime, C.S., Durr, A., Melki, J., Lyon-Caen, O., Agid, Y., et al. (1994) Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. Hum Mol Genet., 3,1569-1573.
van Deutekom, J.C.T., Hofker, M.H., Romberg, S., van Geel, M., Rommens, J., Wright, T.J., Hewitt, J.E., Padberg, G.W., Wijmenga, C., Frants, R.R. (1995) Search for the FSHD gene using cDNA selection in a region spanning 100 kb on chromosome 4q35. Muscle & Nerve, Suppl 2, S19‑S26.
Boerman, R.H., Ophoff, R.A., Links, T.P., van Eijk, R., Sandkuijl, L.A., Elbaz, A., Vale-Santos, J.E., Wintzen, A.R., van Deutekom, J.C., Isles, D.E., et al. (1995) Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis. J Med Genet., 32, 44-47.
Tijssen, M.A., Shiang, R., van Deutekom, J., Boerman, R.H., Wasmuth, J.J., Sandkuijl, L.A., Frants, R.R., Padberg, G.W. (1995) Molecular genetic reevaluation of the Dutch hyperekplexia family. Arch Neurol., 52, 578-582.
van Deutekom, J.C.T., Lemmers, R.J.L.F., Grewal, P., van Geel, M., Romberg, S., Dauwerse, H.G., Wright, T.J., Padberg, G.W., Hofker, M.H., Hewitt, J.E., Frants, R.R. (1996) Identification of the first gene (FRG1) from the FSHD region on human chromosome 4q35. Hum. Mol. Genet., 5, 581-590.
Grewal, P.K., van Deutekom, J.C.T., Frants, R.R., Hewitt, J.E. (1996) A search for genes in the facioscapulohumeral muscular dystrophy region. Biochem. Society Transactions, 24, 282S.
van Deutekom, J.C.T., Bakker, E., Lemmers, R.J.L.F., van der Wielen, M.J.R., Bik, E., Hofker, M.H., Padberg, G.W., Frants, R.R. (1996) Evidence for subtelomeric exchange of 3.3 kb tandemly repeated units between chromosomes 4q35 and 10q26: implications for genetic counseling and etiology of FSHD1. Hum. Mol. Genet., 5, 1997-2003.
Grewal, P.K., van Deutekom, J.C.T., Mills, K.A., Lemmers, R.J.L.F., Mathews, K.D., Frants, R.R., Hewitt, J.E. (1997) The mouse homologue of FRG1, a candidate gene for FSHD, maps to the syntenic region of chromosome 8. Mamm Genome., 8, 394-398.
Floyd, S.S., Booth, D.K., Van Deutekom, J.C.T., Day, C.S., and Huard J. (1997) Autologous Myoblast Transfer: A combination of myoblast transplantation and gene therapy. Basic Appl Myol, 7, 241-250.
Van Deutekom, J.C.T., Hoffman, E.P., and Huard J. (1998) Muscle Maturation: Implications for Gene Therapy. Mol Med Today, 4, 214‑220.
Van Deutekom, J.C.T., Floyd, S.S., Booth, D.K., Oligino, T., Krisky, D., Marconi, P., Glorioso, J.C., and Huard, J. (1998) Implications of maturation for viral gene delivery to skeletal muscle. Neuromuscul Disord, 8, 135‑148.
Qu, Z., Balkir, L., van Deutekom, J.C.T., Robbins, P.D., Pruchnik, R., and Huard, J. (1998) Development of approaches to improve the cell survival in Myoblast Transfer Therapy. J Cell Biol, 142, 1257‑1267.
Lemmers, R.J., van der Maarel, S.M., van Deutekom, J.C., van der Wielen, M.J., Deidda, G., Dauwerse, H.G., Hewitt, J., Hofker, M., Bakker, E., Padberg, G.W., Frants, R.R. (1998) Inter‑ and intrachromosomal sub‑telomeric rearrangements on 4q35: implications for facioscapulohumeral muscular dystrophy (FSHD) aetiology and diagnosis. Hum Mol Genet, 7, 1207‑1214.
Van Deutekom, J.C.T., Cao, B., Pruchnic, R., Wickham, T.J., Kovesdi, I., Huard, J. (1999) Extended tropism of an adenoviral vector does not circumvent the maturation-dependent transducibility of mouse skeletal muscle. J Gene Med., 1, 393-399.
Ginjaar, I.B., Kneppers, A.L., vd Meulen, J.D., Anderson, L.V., Bremmer-Bout, M., Van Deutekom, J.C., Weegenaar, J., Den Dunnen, J.T., Bakker, E. (2000) Dystrophin nonsense mutation induces different levels of exon 29 skipping and leads to variable phenotypes within one BMD family. Eur J Hum Genet., 8, 793-796.
van Geel, M., van Deutekom, J.C., van Staalduinen, A., Lemmers, R.J., Dickson, M.C., Hofker, M.H., Padberg, G.W., Hewitt, J.E., de Jong, P.J., Frants, R.R. (2000) Identification of a novel beta-tubulin subfamily with one member (TUBB4Q) located near the telomere of chromosome region 4q35. Cytogenet Cell Genet., 88, 316-321.
Van Deutekom, J.C., Bremmer-Bout, M., Janson, A.A., Ginjaar, I.B., Baas, F., Den Dunnen, J.T., Van Ommen, G.J. (2001) Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum Mol Genet.,10,1547-1554.
Havenga, M.J., Lemckert, A.A., Ophorst, O.J., van Meijer, M., Germeraad, W.T., Grimbergen, J., van Den Doel, M.A., Vogels, R., van Deutekom, J.C., Janson, A.A., de Bruijn, J.D., Uytdehaag, F., Quax, P.H., Logtenberg, T., Mehtali, M., Bout, A. (2002) Exploiting the natural diversity in adenovirus tropism for therapy and prevention of disease. J Virol., 76, 4612-4620.
Aartsma-Rus, A., Bremmer-Bout, M., Janson, A.A., den Dunnen, J.T., van Ommen, G.J., and van Deutekom, J.C.T. (2002) Targeted antisense-induced exon skipping as a gene correction therapy for Duchenne muscular dystrophy. Neuromuscul. Disord., 12, S71-77.
Aartsma-Rus, A., Janson, A.A., Kaman, W.E., Bremmer-Bout, M., den Dunnen, J.T., Baas, F., van Ommen, G.J., and van Deutekom, J.C.T. (2003) Therapeutic antisense-induced exon skipping in muscle cells from 6 different DMD patients. Hum Mol Genet., 12, 907-914.
Van Deutekom, J.C.T. and van Ommen, G.J.B. (2003) Advances in Duchenne Muscular Dystrophy gene therapy. Nat. Rev. Genet., 4, 774-783.
Aartsma-Rus, A., Janson, A.A., Kaman, W.E., Bremmer-Bout, M., van Ommen, G.J.B., den Dunnen J.T. and van Deutekom, J.C.T. (2004) Antisense-induced multi-exon skipping for DMD makes more sense. Am. J. Hum. Genet., 74, 83-92.
Aartsma-Rus, A., Kaman, W.E., Janson, A.A., Bremmer-Bout, M., den Dunnen, J.T., van Ommen, G.J.B., and van Deutekom, J.C.T. (2004) Comparative analysis of antisense oligonucleotide analogs for targeted exon skipping in muscle cells. Gene Ther.,11, 1391-1398.
Bremmer-Bout, M., Aartsma-Rus, A., de Meijer, E.J., Kaman, W., Janson, A.M., Vossen, R.H.A.M., van Ommen, GJ.B., den Dunnen, J.T., and van Deutekom, J.C.T. (2004) Targeted exon skipping in hDMD mice: a model for direct pre-clinical screening of human-specific antisense oligonucleotides. Mol Ther.,10, 232-240.
Sterrenburg, E., Turk,, R., 't Hoen, P.A., van Deutekom, J.C., Boer, J.M., van Ommen, G.J., den Dunnen, J.T. (2004) Large-scale gene expression analysis of human skeletal myoblast differentiation. Neuromuscul Disord., 14, 507-518.
Rijkers T, Deidda G, van Koningsbruggen S, van Geel M, Lemmers RJ, van Deutekom JC, Figlewicz D, Hewitt JE, Padberg GW, Frants RR, van der Maarel SM. (2004) FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating primary myoblast cultures of FSHD patients. J Med Genet., 41, 826-836.
Van Deutekom, J.C. (2005) The 'pro-sense' approach to Duchenne muscular dystrophy. Eur J Hum Genet. 13, 518-519.
Aartsma-Rus,A., De Winter,C.L., Janson,A.A.,
Kaman,W.E., van Ommen,G.J., Den Dunnen,J.T., and van Deutekom,J.C. (2005) Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping:
indication for steric hindrance of SR protein binding sites. Oligonucleotides.,
15, 284-297.
't Hoen,P.A.,
van der Wees,C.G., Aartsma-Rus,A., Turk,R., Goyenvalle,A., Danos,O.,
Garcia,L., van Ommen,G.J., Den Dunnen,J.T., and van Deutekom,J.C. (2006) Gene expression profiling to monitor therapeutic and adverse effects of antisense
therapies for Duchenne muscular dystrophy. Pharmacogenomics., 7,
281-297.
Aartsma-Rus,A., Janson,A.A., Heemskerk,J.A.,
De Winter,C.L., van Ommen,G.J., and van Deutekom,J.C. (2006) Therapeutic
modulation of DMD splicing by blocking exonic splicing enhancer sites with
antisense oligonucleotides. Ann.N.Y.Acad.Sci., 1082, 74-76.
Aartsma-Rus,A., van Deutekom,J.C.,
Fokkema,I.F., van Ommen,G.J., and Den Dunnen,J.T. (2006) Entries in the Leiden
Duchenne muscular dystrophy mutation database: an overview of mutation types and
paradoxical cases that confirm the reading-frame rule. Muscle Nerve,
34, 135-144.
Aartsma-Rus,A., Kaman,W.E., Weij,R., Den Dunnen,J.T., van Ommen,G.J., and
van Deutekom,J.C. (2006) Exploring the frontiers of therapeutic exon skipping
for Duchenne muscular dystrophy by double targeting within one or multiple exons.
Mol Ther, 14, 401-407.
Aartsma-Rus,A., Janson,A.A., van Ommen,G.J., and van Deutekom,J.C. (2007) Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy.
BMC.Med.Genet., 8, 43.
Arechavala-Gomeza, V., Graham, I.R., Popplewell, L.J., Adams, A.M., Aartsma-Rus, A., Kinali, M., Morgan, J.E., van Deutekom, J.C.T., Wilton, S.D., Dickson, G. and Muntoni, F. (2007) Comparative analysis of antisense oligonucleotide sequences for targeted skipping of exon 51 during dystrophin pre-mRNA splicing in human muscle. Hum Gen Ther, epub Sept 3.
Van Deutekom, J.C.T., Janson, A.A.M., Ginjaar, H.B., Frankhuizen W.S., Aartsma-Rus, A., Bremmer-Bout, M. den Dunnen, J.T., Koop, K., van der Kooi, A.J., Goemans, N.M., de Kimpe, S.J., Ekhart, P.F., Venneker, E.H., Platenburg, G.J., Verschuuren, J.J. and van Ommen, G-J.B. (2007) Local dystrophin restoration with antisense oligonucleotide PRO051.. N Engl J Med 357: 2677-86
Van Ommen, G-J.B., Van Deutekom, J.C.T. and Aartsma-Rus, A. (2008) The therapeutic potential of antisense-mediated exon skipping. Curr Opin Mol Ther 10:140-9
Aartsma-Rus A, van Vliet L, Hirschi M, Janson, A.A., Heemskerk, J.A. De Winter, C.L...Van Deutekom, J.C.T. et al. (2008) Guidelines for antisense oligonucleotide design and insight in splice modulating mechanisms. Mol Ther 2008; in press
Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar HB...Van Deutekom, J.C.T. et al. (2008): Applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Human Mutation; Accepted manuscript