Research and publications

Lysosomal Disorders Unit

Current clinical trials at CUH | Key publications

At CUH we are always looking to improve both the quality of care and the treatment options available to all our patients. We are actively involved in both academic and clinical research, funded independently and in conjunction with our partners in the pharmaceutical industry.

From time to time there may be the opportunity for patients to participate in these studies and your physician will let you know whether it is suitable for you.

Current clinical trials at CUH:


Amicus 1001-012 ATTRACT study

This is a phase 3 multicentre study sponsored by the pharmaceutical company Amicus.  Migalastat is a new (unlicensed) tablet treatment. This study is looking at  both the safety and efficacy of this treatment in patients with a very specific genotype.

Current status: Recruitment now closed

Fabrystudy – The ATTRACT study


Zavesca switch study

This is a Phase 3b multi centre study sponsored by the pharmaceutical company Actelion. Miglustat (Zavesca) is a tablet treatment currently licensed for use in Gaucher disease. This study is looking at whether stable type 1 Gaucher patients continue to remain stable when switched to Zavesca for a period of  2 years. 

Current status: trial complete – report due soon

AT2101 naïve study

This is a Phase 2 multi centre study sponsored by the pharmaceutical company Amicus. Plicera (AT2101) is a new (unlicensed) tablet  treatment. This study is looking at safety and side effects in treatment naïve patients (ie patients who have not received ERT/SRT) with type 1 Gaucher disease. It is also hoped to see some efficacy in managing disease/symptoms. This treatment is thought to work as a pharmacological chaperone rather than as with Enzyme replacement therapy (ERT) or Substrate reduction therapy (SRT) and the intention is to treat eligible patients with AT2101 for about 6 months.

Current status: trial complete – report due soon

Gaucher - Genzyme GZGD02507 ENGAGE & GZD02607 ENCORE.

These are 2 trials:  ENGAGE – for new patients and ENCORE for existing Gaucher patients. The trials aim to look at safety and efficacy of an oral preparation (eliglustat)  in Gaucher patients.

Current status: trials completed – extension phase ongoing

Genzyme studies

Gaucher - Protalix  PB06-002

This is a phase 3 openlabel switchover study  of intravenous  infusion of prGCD. This is an ERT derived from a plant cell for treating gaucher disease. The trial will be  looking at both safety and efficacy.

Current status: trial completed report awaited


Currently none - watch this space.

Lysosomal Acid Lipase Deficiency/ Cholesterol ester Storage Disease (CESD)


This is a phase 1/2 study sponsored by the pharmaceutical company Synageva.  SBC-102 is a replacement form of the natural enzyme (Lysosomal Acid Lipase) administered by intravenous infusion every 2 weeks.  The study aims to find out whether the drug is safe and whether it has any side effects- this is the first time the drug has been studied in humans and the infusions will take place in our purpose built hospital research facility. – NCT01307098

Current status: recruitment now closed - trial completed report awaited


This is a phase 3 study sponsored by the pharmaceutical company Synageva.  SBC-102 is a replacement form of the natural enzyme (Lysosomal Acid Lipase) administered by intravenous infusion every 2 weeks.  The study aims to find out whether the drug is safe and  how effective it is in a placebo controlled double blind trial.

Current status: recruitment now closed NCT01757184


This is a descriptive natural history study looking at the course of the disorder before any treatments become available. The trial requires participants to complete a set  of questionnaires & to allow  access to their medical records. The re is the option to participate in a small sub section of the study having a liver MRI in Newcastle.

Current status: trial completed report awaited


Other research:


Bone project

A multi centre UK  adult/children study looking at progression and features of Gauchers disease including its effects on mobility and quality of life. recruitment now completed – report writing /analysis ongoing.

Funded by the Gaucher Association


Gene therapy in mouse model of Sandhoff disease  

Progress continues

Professor Timothy Cox - Department of Medicine, University of Cambridge



Genetic Variation of LIMP-2 in neuronopathic Gaucher Disease

This is a multi centre UK study coordinated by Dr Nick Smith looking at genetic changes in LIMP -2 – a modifier gene thought to be associated with Gaucher disease. The intention is to compare findings between those who have neurology symptoms with those who do not. Recruitment will be starting imminently.  If you would like to know more please contact us.


International, multicentre, long term observational database studies

FOS & HOS (Fabry & Hunter Outcome surveys  - Shire)
Research nurse: Debbie Hugh

Genzyme registries (Gaucher, Fabry & Pompe)
Research nurse: Jill Daines

IS3 safety surveillance program (Zavesca - Actelion)


Penninsular Medical School/HTA project

A longitudinal cohort study of people with lysosomal storage disorders  

The Peninsula Medical School, in collaboration with the treatment centres and the support groups, is looking at how effective and cost effective therapies for lysosomal disorders are. 

Current status: trial complete – report awaited


Therapeutic targeting of enzyme glycoforms in Fabry and Hunter 

MPS society funded research

Patient recruitment continues (Cambridge study only).

This study is looking at how therapy gets to where it is needed and whether this can be improved.


Study of the aetiology and prodrome of Parkinson’s disease:

Joint project with the Royal Free Hospital. The  aim is  to study individuals  and their families  with gaucher disease and look for any relationships with Parkinson’s disease

Current status: project completed – report awaited.


Generation of patient specific stem cells for research in neurodegenerative disorders of CNS

Joint project with  Dr Roger Barker, Consultant Neurologist, University of Cambridge

Status: currently recruiting  please do contact us if you are


The utility of ALT and HDL for identifying Lysosomal Acid Lipase Deficiency

Joint project with  Professor Tim Reynolds, Consultant Chemical Pathologist, Queens Hospital, Burton –on-Trent.

Status: currently recruiting please do contact us if you are


Please do contact us if you would like to receive further information about any of these or other Lysosomal disorders research programs you are aware of.

Research interests

We work closely with Professor Cox's team in the university department of medicine:

Professor Timothy Cox - Department of Medicine, University of Cambridge

The broad aim of our scientific studies is to improve the diagnosis, monitoring and treatment of lysosomal disorders: we thus investigate the natural course and molecular pathogenesis of these diseases; we have discovered novel biomarkers and have introduced innovative treatments. As part of the latter, a gene transfer programme has been initiated; this involves pre clinical research designed to translate our recent therapeutic discoveries rapidly from the laboratory to the clinic. 

Some of our current research interests include:

Biomarkers of disease

Pathogenesis of Gaucher disease

Gene therapy - with a specific interest in the Lysosomal storage disorders that cause neurological disease

Key publications

Professor Cox

Professor Timothy Cox - Department of Medicine, University of Cambridge

Mistry, P.K., Wraight, E.P. and Cox, T.M. (1996)
Delivery of proteins to macrophages: implications for treatment of Gaucher Disease.  Lancet 348: 1555-1559.

Moran, MT, Schofield J., Hayman A.R., E. Young, Shi G-P and Cox T.M.(2000) Pathologic gene expression in Gaucher’s disease with upregulation of cysteine proteinases including osteoclastic Cathepsin K. Blood 56: 1969-1978.

Cox, T.M. (2001) Gaucher’s disease: understanding the molecular pathogenesis of sphingolipidoses. Journal of Inherited Metabolic Disease 24: (suppl.2): 97-105.Boot R.G., Verhoek M., de Cost M, Hollak CE, Maas M, Bleijtevens B., Van Breemen  MJ. van Meurs M., Boven LA., Laman JD., Moran MT, Cox TM.,  Aerts JM (2004)  Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate  marker for assessing therapeutic intervention. Blood 103: 33-39.

Deegan, PB., Moran, M-T., McFarlane, I., Schofield, JP., Boot, RG.,      Aerts, JMFG., and Cox, TM. (2005) Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease. Blood Cells, Molecules and Disease 35:259-267

Cox T., Lachmann R., Hollak C., Aerts J., van Weely S., Hrebicek M., Platt F., Butters T., Dwek R., Moyses C., Gow I., Elstein D., Zimran A. (2000)  A Novel Oral Treatment of Gaucher’s Disease with N- butyldeoxynojirimycin (OGT 918) to decrease Substrate Biosynthesis. Lancet 355: 1481-1485

Elstein D., Hollak C., Aerts JM, van Weely S., Maas M., Cox T.M.,  Lachmann RH., Hrebicek M., Platt FM., Butters TD., Dwek RA, Zimran      A (2004)  Sustained  therapeutic effects of oral miglustat (Zavesca, N-     butyldeoxynojirimycin, OGT 918) in  type 1 Gaucher disease. Journal of Inherited Metabolic Disease 27: 757-766.

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. Neurobiology of Disease 16: 654-658.

Whitfield PD., Calvin J, Hogg S, O’Driscoll E., Halsall D., Burling K., Maguire G., Wright N., Cox TM, Meikle PJ.,and  Deegan, PB. (2005) Monitoring enzyme replacement therapy in Fabry disease – role of urine globotriasoylceramide. Journal of Inherited Metabolic Disease 28: 21-33.

Cachón-González M.B., Wang S.Z., Lynch A., Ziegler R., Cheng, SH &  Cox, TM. (2006) Effective gene therapy in an authentic model of Tay-Sachs related diseases. Proceedings of the National Academy of Sciences (USA) 103: 10373-10378.

Cox, T.M., Platt, F.M. and Aerts, J.M.F.G. (2007)
Medicinal Use of Iminosugars Chapter 13, in: 
Iminosugars from Synthesis to Therapeutic Applications
pp.295-328. Edited P. Compain & O. Martin, Wiley, Chichester, UK.

Cox, T.M. (2008) Gaucher’s Disease. A Model Disorder for 
Therapeutic Exploration of the Lysosome, in: Mechanisms of
Disease, Edited by S.Tomlinson, A.M. Heagarty, A.P. Weetman,
R.A. Malik, 2nd edition, Cambridge University Press, pp.42-68. 

Chen Y, Allegood J, Liu Ying, Wang E, Cachón-González MB, 
Cox TM, Merrill A, Sullards M. (2008) Imaging MALDI Mass Spectrometry Using an Oscillating Capillary Nebulizer Matrix Coating System and Its Application to Analysis of Lipid in Brain from a Mouse Model of Tay-Sachs/Sandhoff Disease. Analytical Chemistry e-pub 4 March

Cox, T.M. Aerts, J.M.F.G., Belmatoug, N., Capellini, M.D., 
vom Dahl, S., Goldblatt, J., Grabowski, G.A., Hollak, C.E.M., 
Hwu, P., Maas, M., Martins, A.M., Mistry, P.K., Pastores, G.M.,
Tylki-Szymanska, A., Yee, J. and  Weinreb, N. (2008)
Management of non-neuronopathic Gaucher disease with
special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. Journal of Inherited Metabolic Disease 2008 Jun;31(3):319-36. Epub 2008 May 23.

Roos, J.C.P., Lachmann, R. H.,Carpenter, R.H.S., Cox, T.M. (2008)
Saccadic latency as an objective biomarker of cerebral injury in lysosomal storage disease. Lancet Neurology (submitted)

Wang, S.Z., Cachón-González, M.B., Stein, P.E., Lachmann, R.H.,
Woods, G., Corry, P.C., Wraith, J.E.,  Cox, T.M. (2008)
Molecular analysis of the human HEXB gene in Juvenile
Jatzkewitz-Sandhoff disease in two extended Pakistani
pedigrees. Human Genetics (submitted)


Abstracts for presentation

M. B. Cachón-González, S. Wang, R. Ziegler, S. H. Cheng & T. M. Cox (2008) Functional Outcome and Survival Correlates with Time of Gene Transfer and Viral Titres in a Mouse Model of Sandhoff Disease (Boston: Am. Soc. Hum. Gene Therapy)

E.V. Pavlova, M.T. Moran, P.B. Deegan, T.M. Cox (2008)
Enhanced Abundance and Processing of Cathepsin S: 
a potential Biomarker of Gaucher disease (Budapest: EWGGD)

E.V. Pavlova, J.E. Tindall, D.A. Hughes, A.Mehta, J.E. Wraith, T.M. Cox, and P.B. Deegan (2008) Biomarkers of Avascular Necrosis in Gaucher Disease (Budapest: EWGGD)

Deegan PB, Tindall JE, Stein PE, Mehta A, Hughes DA, Wraith JE, Waldek S, Cox TM (2008). 
Osseous Complications of Gaucher Disease: a National Survey (Paris: 4th X-LSD Meeting) 

M.B. Cachón-González, S.Z. Wang and T.M Cox (2007)
Combination Therapy for Tay-Sachs and Related Neurodegenerative Diseases (Bilbao: Int. Soc. Sphingolipid Res.)

Cox, T.M. (2007) Prospects for Stem-Cell and Gene Therapy for Lysosomal Storage Disorders (Porto: Treatment of Inborn Errors)

Marchesan D, Cox TM and Deegan PB (2007)
Mechanism of Uptake of Therapeutic Alpha Galactosidase A in Cells Relevant to Fabry Disease (Perrugia: Eur. Study Group Lysosomal Diseases)

M.B. Cachón-Gonzaléz, S. Z Wang, R. Ziegler, S H Cheng 
and T M Cox.(2007) Successful Gene Therapy for Tay-Sachs and related Neurodegenerative Diseases (Bristol: Association of Physicians of Great Britain & Ireland)

Lachmann RH, Wright N, Parker A, Ramaswami U, Coleman M, Roos J, Bernstein R, Gillard J, Harding S, Platt FM, Wraith E, Cox TM (2006) Substrate reduction therapy in Sandhoff disease: evidence for improvement in nervous function in patients treated with miglustat  (Japan: SSIEM J. Inherit. Metab. Dis)