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Platt Lab, Personnel     Lab Scientists Prof. Fran M. Platt Celeste Chuang Dr. Emyr Lloyd-Evans Ksenia Peterneva Dr. David A. Priestman Viv Reeve Dave Smith Dr. Annie Speak Danielle Taylor-te Vruchte Dr. Kerri-Lee Wallom Dr. Ian Williams Oscar Chen ______________________________________________________________________________________________________     Publications @ PubMed Click for my papers Related Images > Oxford University Press Site Fran M. Platt, PHD, Professor Background Professor Platt obtained a BSc in Zoology at Imperial College University of London and a PhD from University of Bath, in Animal Physiology. She was a post-doctoral fellow at Washington University Medical School in St Louis, USA. Since returning to the UK in 1989 (to the Biochemistry Department, University of Oxford) she has focused on how the abnormal accumulation of glycosphingolipids results in pathology in the lysosomal storage diseases. She was a Lister Institute Senior Research Fellow from 1996-2002. A major focus of her work has been on the development of substrate reduction therapy (SRT) to treat several of these disorders. Proof of principle of SRT was demonstrated in mouse models of these primarily neurodegenerative diseases.  Dr Platt’s research, in collaboration with Dr Terry Butters, has led to the development of a drug (miglustat/Zavesca) for glycosphingolipid storage disease therapy. In 2002 miglustat was approved by the regulatory authorities for clinical use in the commonest of these diseases (type 1 Gaucher disease) and is currently in clinical trials in the neuronopathic forms of these disorders. Her current interests focus on the cell biology and pathobiology of glycosphingolipids and on the development of novel therapies for treating diseases resulting from defects in gycolipid metabolism. She moved to the Department of Pharmacology in April 2006. Key Research Areas • The cell biology of glycosphingolipids • How defects in glycosphingolipid metabolism cause disease • The effects of glycosphingolipid storage on the immune system • Development of cell based assays to monitoring storage disease patients receiving experimental therapies • The development of novel therapies for diseases caused by defects in glycolipid metabolism < to top         Publications @ PubMed Click for my papers Related Images   Celeste Chuang PhD Project • The mechanism behind imino sugar-induced infertility in male mice. • The biological role of the FAPP2 glycolipid-transfer protein in glycosphingolipid biosynthesis. Techniques • Glycosphingolipid analysis by HPLC. • Sub-cellular fractionation of mouse testicular cells. • Imino-sugar-affinity chromatography.    Publications Wu PL, Lee SC, Chuang CC, Mori S, Akakura N, Wu WG, and Takada Y. (2006) Non-cytotoxic cobra cardiotoxin A5 binds to integrin αvβ3 and inhibits bone resorption: Identification of cardiotoxins as non-RGD integrin-binding proteins of the Ly-6 family. J. Biol. Chem.281, 7937–45. D’Angelo G, Polishchuk E, Di Tullio1 G, Santoro M, Di Campli1 A, Godi1 A, West G,  Bielawski J, Chuang CC, van der Spoel AC, Platt FM, Hannun YA, Polishchuk R, Mattjus P, and De Matteis A. (2007) Non-vesicular transport of glucosylceramide via FAPP2is required for glycosphingolipid synthesis and membrane transport to the plasma membrane. Nature. 449(7158), 62-7. Walden CM, Sandhoff R, Chuang CC, Yildiz Y, Butters TD, Dwek RA, Platt FM, van der Spoel AC. (2007) Accumulation of glucosylceramide in murine testis, caused by inhibition of beta-glucosidase 2: Implications for spermatogenesis. J. Biol. Chem. 282, 32655-64. Rabionet M, van der Spoel AC, Chuang CC, von Tümpling-Radosta B, Litjens M, Bouwmeester D, Hellbusch CC, Körner C, Wiegandt H, Gorgas K, Platt FM, Gröne HJ, Sandhoff R. Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: A link to ceramide synthase-3. (2008) J. Biol. Chem. Epub 2008 Feb 27. Funding Sources Schering AG, Berlin < to top         Publications @ PubMed Click for my papers Related Images Emyr Lloyd-Evans, PhD Background I study the basic cell biology of the lysosome and how lysosomal function is altered in neurodegenerative disorders. The lysosome has long been known to be the cellular recycling centre. However, emerging evidence points to important roles for lysosomes in cellular signalling, immunology and wound healing. My research investigates the machinery that regulates normal lysosomal function and the events that unfold in neurodegenerative lysosomal storage disorders, following mutation or inhibition of this machinery (Fig. 1). I am particularly interested in the mechanisms that regulate lysosomal calcium homeostasis and the subsequent requirement of lysosomal calcium release for normal endocytic lipid transport and recycling (Fig. 2).   My current research focuses on abnormal lysosomal calcium homeostasis in the lysosomal disorders Niemann-Pick C1 and mucolipidosis type IV. Using the information gained from this research we are developing new therapies that target early steps in the pathogenesis of these disorders. I am also interested in the secondary lysosomal dysfunction that occurs in other disorders such as cystic fibrosis, tuberculosis and Smith-Lemli-Opitz Syndrome. We have discovered some mechanistic similarities between these disorders and Niemann-Pick C1 that we are using to develop novel therapies.   Current research interests and projects Cell biology of Niemann-Pick C and function of the NPC1 protein in neuronal lysosomal lipid transport and calcium homeostasis. The role of altered NPC1 function in inducing secondary lysosomal storage in disorders such as tuberculosis, cystic fibrosis and the cholesterol biosynthetic disease Smith-Lemli-Opitz. Function of Mucolipin 1 (TRPML1) in maintaining lysosomal ion homeostasis, with respect to mucolipidosis type IV a disease in which this protein is mutated. Requirement of the lysosomal calcium store for normal endocytosis and its involvement in disease processes. Development of novel therapies for neurodegenerative disorders with abnormal lysosomal function. Collaborations Dr. Forbes Porter, NIH, USA. Secondary NPC1 phenotype in Smith-Lemli-Opitz Syndrome. Prof. Antony Galione, Dept. Pharmacology, University of Oxford. Defective lysosomal calcium in NPC1. Dr. Mukram Mackeen, Dept. Chemistry, University of Oxford. Development of natural product therapies for lysosomal storage disorders. Funding Sources Birth Defects Foundation Newlife, UK National Niemann-Pick disease Foundation, USA SLOS Foundation, USA SPARKS (UK) < to top         Ksenia Peterneva Current research interests and projects The project focuses on the accelerated development of new ways of monitoring and treating Niemann-Pick disease type C (NPC). Currently, the research focuses on cell based screening assays and combination therapy in a mouse model of NPC disease. Funding Sources NPC-SOAR (a USA-based consortium of NPC charities) < to top         Publications @ PubMed Click for my papers David A. Priestman, PhD 1. The effects of disrupted glycosphingolipid biosynthesis. Human GM3 Synthase Deficiency: A Novel Form of Hereditary Childhood  Epilepsy. This is the first proven example of a disease resulting from a defect in ganglioside biosynthesis. This disorder is inherited as an autosomal recessive trait and results in an infantile onset symptomatic epilepsy syndrome associated with developmental stagnation and blindness. It seems that a lack of complex gangliosides and/or the accumulation of precursors of ganglioside synthesis result in neuronal instability in the CNS. We are currently elucidating the mechanism(s) through which this disease phenotype develops. These studies will shed light on ganglioside functions in the brain and offer new insights for the development of therapies for this novel form of childhood epilepsy. (link to Simpson et al, Nat Gen) 2. The Fabry mouse The mouse model of Fabry disease has targeted disruption of the gene encoding alpha-galactosiadase A.  These mice show a complete lack of enzyme activity and have significant storage of Gb3 in most organs and tissues.  Unlike human patients with Fabry disease the mice have a normal lifespan and don’t develop renal or cardiovascular complications leading pathology.  However, the mild phenotype in the mouse makes it amenable to the evaluation of new therapeutic strategies.  In this regard, we have been able to show that Fabry mice have endothelial cell dysfunction, which responds to treatment with NB-DNJ (add links to Heare et al papers).  In addition to this work, we have also been studying the biochemistry, cardiophysiology and neurophysiology of the Fabry mice.   3. Glycosphingolipid profiling in tissues from mouse model of the human lysosomal storage disorders We study several mouse models of human lysosomal storage disorders (LSDs) as they are of considerable value for understanding disease pathophysiology and development of new LSD therapies.  In a significant proportion of the human LSDs there is primary or secondary storage of glycosphingolipids (GSLs) and this is also true of the mouse models.  Using a highly sensitive and quantitative HPLC method, we have analysed and quantified GSLs in brain, liver, kidney, spleen, serum, thymus, heart, lungs and testis of control mice and several mouse models of human disease.  The data acquired from these studies are accessible here  (LINK). 4. The molecular mechanism of weight-loss in mice treated with NB-DNJ Mice treated with relatively high doses of the imino sugar drug NB-DNJ (miglustat) lose weight in the form of adipose tissue.  We have recently established that this weight loss is a result of central appetite suppression (link to pdf here) and that imino sugars may prove to be useful as a therapy for obesity.  Although NB-DNJ causes appetite suppression when injected into the brain, its precise mechanism of action in the central nervous system remains unknown. Funding Sources Epilepsy Research UK The Wellcome Trust, UK < to top               Viv Reeve Background Genotyping technician supporting the development of  therapies for lysosomal storage diseases,  studying the effects of novel clinical intervention strategies in mouse models of these disorders Funding Sources NPC-SOAR (a USA-based consortium of NPC charities)         < to top         Publications @ PubMed Click for my papers Dave Smith Background I am studying the effects of adjunctive therapies alone or in combination with substrate reduction therapy (SRT) in a mouse model of NPC1 disease. We plan on using the information gained from these studies (funded by NNPDF) to aid in the design of future clinical trials in patients with NPC. Publications Jeyakumar M, Smith DA, Williams IM, Borja MC, Neville DC, Butters TD, Dwek RA, Platt FM. (2004) NSAIDs increase survival in the Sandhoff disease mouse: synergy with N-butyldeoxynojirimycin. Ann. Neurol. 56(5), 642-9.  Andersson U, Smith D, Jeyakumar M, Butters TD, Borja MC, Dwek RA, Platt FM. (2004) Improved outcome of N-butyldeoxygalactonojirimycin-mediated substrate reduction therapy in a mouse model of Sandhoff disease. Neurobiol. Dis. 16(3), 506-15.  Jeyakumar M, Thomas R, Elliot-Smith E, Smith DA, van der Spoel AC, d'Azzo A, Perry VH, Butters TD, Dwek RA, Platt FM. (2003) Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain. 126(Pt 4), 974-87.  Jeyakumar M, Smith D, Eliott-Smith E, Cortina-Borja M, Reinkensmeier G, Butters TD, Lemm T, Sandhoff K, Perry VH, Dwek RA, Platt FM. (2002) An inducible mouse model of late onset Tay-Sachs disease. Neurobiol. Dis. 10(3), 201-10. Funding Source National Niemann-Pick Disease Foundation, USA < to top         Publications @ PubMed Click for my papers Annie Speak, PhD Research area I am interested in the role glycosphingolipids play in the immune system. In particular I am interested in presentation of lipids by CD1d, a non-polymorphic MHC class I like molecule, to a subset of T cells known as invariant Natural Killer T (iNKT) cells. iNKT cells are found in rodents, primates and humans. They have an invariant T cell receptor (TCR) with conserved gene segments used in humans and mice. The conservation of iNKT cells is such that human iNKT cells can recognise ligands presented by mouse CD1d and vice versa. iNKT cells are able to very rapidly release cytokines after TCR engagement enabling them to function in the innate immune system. iNKT cells can release both IL-4 and IFN-y (and many others) after TCR engagement. Much research has now established that iNKT cells are important for host defence against multiple pathogens, in linking with the adaptive immune system and may play a role in autoimmune disorders. Despite their important roles in host immunity the ligands that activate iNKT cells are poorly understood. Several pathogen-derived lipids have been identified but the self-lipids that direct iNKT cell selection in the thymus are not characterised. Research focus • Determine the glycosphingolipid content of mouse and human thymus. • Identify any changes in glycosphingolipid profile associated with maturation of mouse and human dendritic cells. • Develop methods for lipid preparation for in vitro testing of iNKT cell activation. Techniques • Normal phase HPLC to study glycosphingolipids. • Lipid chromatography and TLC methods. Funding Source Medical Research Council, UK < to top         Publications @ PubMed Click for my papers Danielle Taylor-te Vruchte Background In work previously sponsored by Action Medical Research and the UK Niemann-Pick Disease Group we have developed assays to evaluate the efficacy of substrate reduction therapy (SRT). SRT (using the drug miglustat) slows the rate of GSL biosynthesis and shows benefit in mouse models of Sandhoff and NPC1. We have developed assays to allow us to monitor the efficacy of SRT using peripheral blood samples from patients. The assays are based upon cell biological changes in response to GSL storage. We are investigating the degree to which the changes we observe in the peripheral blood assays correlates with clinical response in a larger group of patients. We are also involved in a natural history study (sponsored by the NIH) on a large group of untreated NPC patients to determine the range of abnormal baseline values against which treated patients can be compared.  Publications Neville DC, Coquard V, Priestman DA, te Vruchte DJ, Sillence DJ, Dwek RA, Platt FM, Butters TD. (2004) Analysis of fluorescently labeled glycosphingolipid-derived oligosaccharides following ceramide glycanase digestion and anthranilic acid labeling. Anal. Biochem. 331(2), 275-82.  Lachmann RH, te Vruchte D, Lloyd-Evans E, Reinkensmeier G, Sillence DJ, Fernandez-Guillen L, Dwek RA, Butters TD, Cox TM, Platt FM. (2004) Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick disease type C. Neurobiol. Dis. 16(3), 654-8.  te Vruchte D, Lloyd-Evans E, Veldman RJ, Neville DC, Dwek RA, Platt FM, van Blitterswijk WJ, Sillence DJ. (2004) Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J. Biol. Chem. 279(25), 26167-75.  Funding Source Action Medical Research UK < to top         Publications @ PubMed Click for my papers       Kerri-Lee Wallom, PhD Background My current research investigates the role of glycosphingolipids in peripheral nerve regeneration and as targets for novel treatments of autoimmune neuropathies. Guillain Barré syndrome (GBS) is the leading cause of neuromuscular paralysis, affecting 1 in a 1000 individuals worldwide at some point in their lives, and leaving 20% disabled or dead. In many cases, an antibody response to infectious agents inadvertently attacks identical sugar epitopes on gangliosides on the surface of peripheral nerves, leading to severe nerve damage. Current therapies comprise primitive, non-specific immunotherapies that are only partially effective. Antigen depletion is being explored as a novel strategy using NB-DNJ (miglustat) which is already an approved drug for treating type 1 Gaucher disease. The specific aims are to establish the kinetics of GSL depletion induced by NB-DNJ in the mouse PNS and to investigate whether the GSL depletion interferes with the development and functional regeneration of peripheral nerve after autoimmune injury. These studies will investigate the potential of antigen depletion to reduce nerve damage in GBS and therefore potentially provide a novel therapeutic strategy for GBS. Collaborators Prof. Hugh Willison, Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow Funding Source Medical Research Council, UK < to top         Publications @ PubMed Click for my papers Ian M. Williams, PhD.  Background  I study brain development and the neurodegenerative environment in order to understand the processes that lead to neuropathology and to find novel ways in which to repair or alleviate CNS damage.   My previous research involved studying the embryonic and postnatal cerebellum to see how the host brain interacts with transplanted neurons and to understand why transplants work well in developing networks but poorly in the mature CNS.   I am now looking at the neurobiology of CNS disease, using the cerebellar pathology of Niemann-Pick disease type C type 1 (NPC1) as a model to determine how this neurodegenerative disease alters cerebellar development and function. In addition I am exploring how the disease microenvironment influences processes such as the migration and integration of both endogenous and exogenous neurons.  Current research projects Elucidate the neuropathology of NPC1, focusing on the chronology of NPC1 phenotypes in cerebellar projection neurons, the onset of gliosis and the development/maintenance of neuronal networks in the NPC1 cerebellum.    Investigating the mechanism behind the resistance of a subset of cerebellar Purkinje cells to NPC1 disease.    Evaluating the transplantation of cerebellar progenitor cells in NPC1, establishing how the neurodegenerative environment impacts the differentiation, migration and integration of new neurons and how newly added cells may ameliorate disease pathology.      Funding Sources  Niemann-Pick Disease Group (UK)  NNPDF Peter G. Pentchev Research Fellowship < to top         Oscar Chen PhD Project The project focused on the molecular mechanism of altered iron homeostasis in the mouse model of Sandhoff disease.   Currently, we extend our previous studies to the mouse model of Niemann-Pick type C (NPC) disease and investigate the molecular mechanisms which result in altered iron homeostasis. Also, we will use biophysical methods to determine whether the defect is specific to iron or involves other metal ions.   Publication Chen CW, Hwang JJ, Tsai CT, Su YN, Hsueh CH, Shen MJ, Lai LP. (2009) The g.-762T>C polymorphism of the NPC1L1 gene is common in Chinese and contributes to a higher promoter activity and higher serum cholesterol levels.J Hum Genet. 2009; 54 (4):242-7.  Funding Source              Clarendon Fund, Oxford University Press, UK    < to top     Lab Alumni     Publications @ PubMed Click for my papers Related Images Aarnoud C. van der Spoel, PhD Aarnoud C. van der Spoel, Ph.D. Atlantic Research Centre Department of Pediatrics Dalhousie University 5849 University Avenue Halifax, NS B3H 4H7 Canada Phone +1-902-494-7084 Fax +1-902-494-1394 MSc Medical Biology, Utrecht University, The Netherlands PhD Cell Biology & Genetics, Erasmus University, Rotterdam, The Netherlands / St. Jude Children’s Research Hospital, Memphis, TN, USA  Research Interests – Development of Male Germ Cells I am interested in a developmental biological process that takes place throughout adult life: the development of male germ cells. It is important to identify factors that control the course of the development of male germ cells and to understand how they work.  Although multiple proteins have been identified to be required for the development of the male gamete, many features of spermatogenesis are only partially understood in biochemical and molecular terms.  A complementary approach to enhance our understanding of the regulation of this process may lie in giving attention at the metabolic level, to “other biomolecules“.  Our findings and those of others suggest that a potential avenue for intervention in the development of male germ cells may be the targeting of glycosphingolipids and glycoproteins.  Within this framework, I am investigating the following issues. Meiosis of male germ cells & complex glycosphingolipids Complex glycosphingolipids are essential for spermatogenesis, in particular for meiotic cytokinesis, and subsequent development of the haploid germ cells.  A number of complex glycosphingolipids with an unusual lipid moiety have been found to be associated with male germ cells.  It appears that these complex glycosphingolipids are first produced during meiosis, during the pachytene phase, after which their levels rapidly increase.  Together with Dr Roger Sandhoff (German Cancer Research Center, Heidelberg, Germany) I am investigating how complex glycosphingolipids contribute to completion of meiosis of male germ cells, and how they set the stage for the further development of haploid male germ cells. Organelle formation in post-meiotic germ cells & glucosylceramide After completion of meiosis, male germ cells gradually form a specialised secretory vesicle that eventually becomes a prominent component of the spermatozoon.  This secretory vesicle, the acrosome, first appears as a dense-core vesicle.  I have discovered that the early steps in acrosome formation can be regulated by glucosylceramide, a glycosphingolipid.  Elevated levels of glucosylceramide can strongly disturb early acrosome formation.  In collaboration with Richard Oko (Queen’s University, Kingston, Canada) we have seen that such conditions also affect the intracellular transport of acrosomal proteins.  Therefore, I aim to resolve what the role is of glucosylceramide in organelle (acrosome) formation in male germ cells. I am approaching these questions using a combination of pharmacological, biochemical and cell biological methods.  In addition I am following a genetic strategy to identify quantitative trait loci that are linked to acrosome formation; this work is being done in collaboration with Dr Richard Mott and Dr Ioannis Ragoussis (Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK). < to top         Publications @ PubMed Click for my papers Related Images Barry Boland, PhD (Visiting Fellow) Dr. Barry Boland Laboratory for Neurodegenerative Research University College Dublin Belfield, Dublin 4, Ireland. Email:barry.boland@ucd.ie Background Neuronal health and long-term viability relies on the constitutive delivery and degradation of intracellular substrates by the endosomal/autophagic/lysosomal system. Impaired degradative flux of substrates through this system leads to an accumulation of undegraded substrates in these compartments, which compromises neuron function and can cause neurodegeneration. My research is aimed at investigating the involvement of endosomal/autophagic/lysosomal dysfunction in the early pathogenesis of Alzheimer’s disease (AD). The primary goal of my research in Dr. Platt’s laboratory is to understand the impact of GSL storage on the intraneuronal metabolism of amyloid precursor protein (APP). Considering different glycosphingolipid (GSL) storage diseases affect different brain regions and organelles to varying degrees, I am interested in studying the impact different GSL storage diseases have on intraneuronal APP metabolism. GSL storage diseases recapitulate many features of accelerated brain aging, such as oxidative stress, neuroinflammation and lipofuscin accumulation. Interestingly, a hallmark of degenerating neurons in one of these diseases, Niemann Pick Type C1 (NPC1), is the endosomal accumulation of aggregated beta-amyloid (Ab) peptide and the presence of neurofibrillary tangles in affected brain regions of human cases.  By understanding how GSL storage affects neuronal endosomal/autophagic/lysosomal function and exploring the occurrence of intraneuronal hallmarks of AD pathogenesis in GSL storage diseases, we aim to identify therapeutic targets that may prove to be useful in correcting neuronal dysfunction and degeneration found in these diseases.   Current Research Delineation of endosomal/autophagic/lysosomal dysfunction in Alzheimer's Disease. Understanding the relevance of altered APP metabolism in GSL storage diseases to AD pathogenesis. Identifying intracellular compartments that accumulate metabolites of APP when endosomal/autophagic/lysosomal system is impaired. Assessing the effect of GSL-lowering therapies on intraneuronal clearance of APP metabolites. Collaborators Dr. Dominic Walsh, Laboratory for Neurodegenerative Research, Conway Institute of Biomedical and Biomolecular Research, University College Dublin. Prof. Ralph Nixon, Department of Psychiatry, New York University School of Medicine/Nathan Kline Institute, U.S.A. < to top         Publications @ PubMed Click for my papers Related Images Jey Mylvaganam Jeyakumar, PhD (Visiting Fellow) Jey M Jeyakumar, PhD Plasticell Ltd Imperial Incubator Besemer Building South Kensington London SW7 2BP Tel: +44 07811 168 177 Fax: +44 02075 941 333 Email:jey@plasticell.co.uk Background Dr Jeyakumar conducts research into the potential of using stem cells for lysosomal storage disorders (LSD). Current research interest include: Neural repair and regeneration strategies for lysosomal storage CNS diseases. Neural stem cells patho-tropism; molecular and cellular characterization. Immune-modulatory capacity of grafted neural stem cells in chronic disease brain. Directed cell delivery; feasibility of intravenous administration of NSCs for global CNS cell delivery. Role of iron in the pathogenesis of the gangliosidoses Neural stem cell (NSC) therapy is attractive in LSDs as stem cells have the capacity to migrate from the site of injection to other areas of the brain to mediate repair. This includes donor-to-recipient cross correction via enzyme secretion-recapture, cell replacement, cell rescue through tropic support, growth factor secretion, neurogenic or gliogenic regulator secretion, and/or other various homeostatic forces such as anti-inflammatory or immune modulatory effects. His research interest focuses on this area and study how the disease environment influences the stem cell behaviour and cellular reparative mechanisms. One of the clinical challenges in treating many neurological disorders is developing therapies that are effective in symptomatic individuals, as most patients exhibit clinical signs at the time of diagnosis. Also, the most appropriate route of stem cell administration, the best approach to achieve an appropriate, functional, and long-lasting integration of transplanted stem cells into the host tissue, are not been resolved. Dr Jeyakumar has recently been involved in a proof-of-principle study that was published in Nature Medicine (April, 2007) jointly with Evan Snyder laboratory. Much of the detail and full potential of this approach remain to be elucidated in further studies. This work is especially relevant to the treatment of neurodegenerative metabolic disorders. Key publications: Lee, J.-P., M. Jeyakumar, F.M. Platt, and E.Y. Snyder et al. (2007) Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nature Medicine, 13(4) p. 439-447. Jeyakumar, M., R.A. Dwek, T.D. Butters, and F.M. Platt (2005) Storage solutions: treating lysosomal disorders of the brain. Nat Rev Neurosci, 6(9): p. 713-725.   < to top