Aldenhoven, M., Jones, S.A., Bonney, D., Borrill, R.E., Coussons, M., Mercer, J., Bierings, M.B., Versluys, B., van Hasselt, P.M., Wijburg, F.A., van der Ploeg, A.T., Wynn, R.F., Boelens, J.J., n.d. Hematopoietic Cell Transplantation for MPS patients is safe and effective: results after implementation of international guidelines. Biology of Blood and Marrow Transplantation. doi:10.1016/j.bbmt.2015.02.011
This treatment paper shows outcomes for 56 Hurler Syndrome patients using new international standards for hematopoietic stem cell transplantation. Experimental groups experienced in increase in survival rates (95% from 78% for transplant done under old standards a decade ago). Updated techniques for donor selection and receiver conditioning are detailed.
Baldo, G., Lorenzini, D.M., Santos, D.S., Mayer, F.Q., Vitry, S., Bigou, S., Heard, J.M., Matte, U., Giugliani, R., 2015. Shotgun proteomics reveals possible mechanisms for cognitive impairment in Mucopolysaccharidosis I mice. Molecular Genetics and Metabolism 114, 138–145. doi:10.1016/j.ymgme.2014.12.301
This paper details the mechanism of disease using proteomics. They show 32 proteins differentially expressed in diseased mice and implicate neuroinflammation and decreased synaptic plasticity as the causes of the diseased state cognitive impairment.
Bie, H., Yin, J., He, X., Kermode, A.R., Goddard-Borger, E.D., Withers, S.G., James, M.N.G., 2013. Insights into mucopolysaccharidosis I from the structure and action of α-L-iduronidase. Nat Chem Biol 9, 739–745. doi:10.1038/nchembio.1357
This structure paper includes structures with bound inhibitors and describes the catalytic mechanism as a double displacement using Glu182 as an acid/base. It also details a structural correlation to the disease state resulting from a P533R mutation.
Chiaro, J.A., O’Donnell, P., Shore, E.M., Malhotra, N.R., Ponder, K.P., Haskins, M.E., Smith, L.J., 2014. Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs. J Bone Miner Res 29, 2610–2617. doi:10.1002/jbmr.2290
This treatment paper showed the effects of neonatal enzyme replacement therapy and simvastatin on spine health in the Hurler Syndrome dog model. While full rescue was not achieved, the ERT minimize the severity of the disease state.
Gabrielli, O., Polonara, G., Regnicolo, L., Petroni, V., Scarabino, T., Coppa, G.V., Salvolini, U., 2004. Correlation between cerebral MRI abnormalities and mental retardation in patients with mucopolysaccharidoses. Am. J. Med. Genet. 125A, 224–231. doi:10.1002/ajmg.a.20515
This paper shows how Hurler Syndrome can manifest itself in the pathophysiology of the central nervous system.
Gatti, R., DiNatale, P., Villani, G.R.D., Filocamo, M., Muller, V., Guo, X.-H., Nelson, P.V., Scott, H.S., Hopwood, J.J., 1997. Mutations among Italian mucopolysaccharidosis type I patients. J Inherit Metab Dis 20, 803–806. doi:10.1023/A:1005323918923
The authors show the frequency of common mutations in the IDUA gene in Italian patients and identify a novel mutation unique to Sicily.
Hinderer, C., Bell, P., Gurda, B.L., Wang, Q., Louboutin, J.-P., Zhu, Y., Bagel, J., O’Donnell, P., Sikora, T., Ruane, T., Wang, P., Haskins, M.E., Wilson, J.M., 2014. Intrathecal Gene Therapy Corrects CNS Pathology in a Feline Model of Mucopolysaccharidosis I. Molecular Therapy 22, 2018–2027. doi:10.1038/mt.2014.135
The authors used a cat model to show the neurological outcomes of gene therapy using spinal cord injections. While the neurological model isn’t fully developed in the cat, the histological evidence showed a full rescue from the disease state, supporting possible future translational therapies.
Heppner, J.M., Zaucke, F., Clarke, L.A., 2015. Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I. Molecular Genetics and Metabolism 114, 146–155. doi:10.1016/j.ymgme.2014.09.012
The authors used genomics and proteomics in the rat model to show how clinical symptoms of the disease, which are often overlooked, are caused. Downregulation of 14 proteins indicate that the extracellular matrix is disrupted early on in the disease state.
Liu, Y., Xu, L., Hennig, A.K., Kovacs, A., Fu, A., Chung, S., Lee, D., Wang, B., Herati, R.S., Mosinger Ogilvie, J., Cai, S.-R., Parker Ponder, K., 2005. Liver-directed neonatal gene therapy prevents cardiac, bone, ear, and eye disease in mucopolysaccharidosis I mice. Mol Ther 11, 35–47. doi:10.1016/j.ymthe.2004.08.027
This paper is the first paper to show a full rescue of clinical symptoms in mice using retroviral gene therapy.
Maita, N., Tsukimura, T., Taniguchi, T., Saito, S., Ohno, K., Taniguchi, H., Sakuraba, H., 2013. Human α-l-iduronidase uses its own N-glycan as a substrate-binding and catalytic module. PNAS 110, 14628–14633. doi:10.1073/pnas.1306939110
This structure paper shows that mannose on the N-glycan of IDUA forms part of the binding site. Kinetics studies showed that deglycosylated protein was less active, indicating the glycan’s role in catalysis as well.
Matte, U., Yogalingam, G., Brooks, D., Leistner, S., Schwartz, I., Lima, L., Norato, D.Y., Brum, J.M., Beesley, C., Winchester, B., Giugliani, R., Hopwood, J.J., 2003. Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients. Molecular Genetics and Metabolism 78, 37–43. doi:10.1016/S1096-7192(02)00200-7
This paper identified 13 novel mutations, and highlighted three repeating mutations, in Brazilian patients with Hurler Syndrome.
Ou, L., Herzog, T., Koniar, B.L., Gunther, R., Whitley, C.B., 2014. High-dose enzyme replacement therapy in murine Hurler syndrome. Molecular Genetics and Metabolism 111, 116–122. doi:10.1016/j.ymgme.2013.09.008
The authors used very high doses of laronidase to cross the blood-brain barrier in enzyme replacement therapy to treat the neurological effects of Hurler Syndrome in mice. They showed that high dosage is successful in achieving BBB crossing and that cognitive function improved in treated subjects.
Poe, M.D., Chagnon, S.L., Escolar, M.L., 2014. Early treatment is associated with improved cognition in Hurler syndrome. Ann. Neurol. 76, 747–753. doi:10.1002/ana.24246
This treatment paper shows the outcomes of 31 patients before, during, and after umbilical cord blood transplantation. It indicates “cure” outcomes for newborns younger than 9 months at the time of treatment and asserts that newborn screening is a key factor in treating the disease.
Scott, H.S., Litjens, T., Hopwood, J.J., Morris, C.P., 1992. A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype. Hum. Mutat. 1, 103–108. doi:10.1002/humu.1380010204
This is the first time W402X, one of the two common mutation that cause severe cases of Hurler Syndrome, was identified.
Resnick, J.M., Whitley, C.B., Leonard, A.S., Krivit, W., Snover, D.C., 1994. Light and electron microscopic features of the liver in mucopolysaccharidosis. Hum. Pathol. 25, 276–286. link
This paper correlates the biochemistry to the macroscopic disease state, specifically in the liver.
Scott, H.S., Litjens, T., Nelson, P.V., Thompson, P.R., Brooks, D.A., Hopwood, J.J., Morris, C.P., 1993. Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes. Am J Hum Genet 53, 973–986.
This paper identifies four novel mutations in the IDUA genes of patients with severe cases of Hurler Syndrome. link
Voskoboeva, E.Y., Krasnopolskaya, X.D., Mirenburg, T.V., Weber, B., Hopwood, J.J., 1998. Molecular Genetics of Mucopolysaccharidosis Type I: Mutation Analysis among the Patients of the Former Soviet Union. Molecular Genetics and Metabolism 65, 174–180. doi:10.1006/mgme.1998.2745
This article shows the frequency of the two common mutations in 25 Hurler Syndrome patients in the Former Soviet Union.
Wang, D., Shukla, C., Liu, X., Schoeb, T.R., Clarke, L.A., Bedwell, D.M., Keeling, K.M., 2010. Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation. Molecular Genetics and Metabolism 99, 62–71. doi:10.1016/j.ymgme.2009.08.002
This paper shows how the disease state features dysfunctions of cells that have lots of intracellular connections.
Watson, H.A., Holley, R.J., Langford-Smith, K.J., Wilkinson, F.L., Kuppevelt, T.H. van, Wynn, R.F., Wraith, J.E., Merry, C.L.R., Bigger, B.W., 2014. Heparan Sulfate Inhibits Hematopoietic Stem and Progenitor Cell Migration and Engraftment in Mucopolysaccharidosis I. J. Biol. Chem. 289, 36194–36203. doi:10.1074/jbc.M114.599944
The authors identify hyper-sulfated extracellular heparan sulfate as a cause of poor engraftment in hematopoietic stem cell transplant treatments.
Wolf, D.A., Lenander, A.W., Nan, Z., Belur, L.R., Whitley, C.B., Gupta, P., Low, W.C., McIvor, R.S., 2011. Direct gene transfer to the CNS prevents emergence of neurologic disease in a murine model of mucopolysaccharidosis type I. Neurobiology of Disease, Autophagy and protein degradation in neurological diseases 43, 123–133. doi:10.1016/j.nbd.2011.02.015
This paper shows a gene therapy strategy for treating diseased rats. It is limited in scope as they injected the vector directly into the brains, but the overall success of the study possibly lays groundwork for further therapy development and ultimate translation into humans.
Yang, J.S., Min, H.K., Oh, H.J., Woo, H.I., Lee, S.-Y., Kim, J.-W., Song, J., Park, H.-D., 2015. A Simple and Rapid Method Based on Liquid Chromatography-Tandem Mass Spectrometry for the Measurement of α-L-Iduronidase Activity in Dried Blood Spots: An Application to Mucopolysaccharidosis I (Hurler) Screening. Ann Lab Med 35, 41–49. doi:10.3343/alm.2015.35.1.41
This paper shows how a new LC-MS/MS method improves upon previously used techniques for diagnosing Hurler Syndrome based on IDUA activity.