Academic Center for Lysosomal and Metabolic Diseases

Last updated: 365 days ago.

The center for Lysosomal and Metabolic diseases, an internationally recognized Academic center of excellence for children and adults, has unique knowledge of rare metabolic diseases and how to address unmet medical needs.

In the oncoming years we will use this knowledge to further improve the perspectives and outcome and quality of care of patients with rare metabolic diseases. The long lasting structural multidisciplinary collaboration between the different departments- Pediatrics, Internal Medicine, Neurology, Hospital Pharmacy, Clinical Genetics and patient organizations and on ad hoc basis with other departments- is unique for Erasmus MC, the Netherlands and internationally.

By combining knowledge and expertise we make "the essential difference" in highly specialized multidisciplinary patient care, diagnostics, education, research and development of innovative therapies. In the oncoming years the center will solidify these unique collaborations. The center will also solidify and expand its collaborations with international expert centers and its leading position in international networks for rare disease such as EPOC (European Pompe Consortium); MetabERN (European Reference Network for Metabolic Diseases), EuroNMD (European Network for Neuromuscular Diseases) and the European Porphyria Network.

These networks are instrumental for research, education, attracting international students, improved transborder health care, and the development of unambiguous guidelines for optimal, individualized treatment regimens. The center has a track record in clinical and translational research. We developed recombinant human alpha-glucosidase as therapy for Pompe disease from bench to bedside and implement more innovative therapies. Translational research focuses on disease modelling, gene therapy, regenerative medicine (using iPS cells and adult stem cells), and RNA based therapies. In the oncoming years we will expand our research and valorize our new intellectual property. The center has been appointed by the Ministry of Health as expert center for the sensible implementation of orphan drugs for lysosomal storage disorders, including Pompe disease, MPS I, II, VI, mannosidosis and NCL and has become a designated expert center by the Minestry of Health (VWS) for Pompe disease, lysosomal storage disorders and hypophosphatasia, Organic acidurias and urea cycle defects and porphyria

It investigates the societal impact of costly orphan drugs in collaboration with the institute of Medical Technology Assessment (iMTA).All these activities are distinctive and highly relevant for the ambition of Erasmus MC.

Academic Center of Excellence

Research Activities

The center and its partners have a long history in studying and treating inborn errors of metabolism, and in particular lysosomal storage diseases. For the development of enzyme replacement therapy we cloned the GAA (alpha-glucosidase) gene, generated a mouse model for the disease, used the gene to explore production of recombinant human alpha-glucosidase GAA in Chines Hamster Ovary (CHO) cells and transgenic animals (mice and rabbits) and were the first worldwide to treat Pompe patients with ERT in 1999. With this achievement Pompe disease became the first treatable inherited neuromuscular disorder.

The knowledge obtained has been and is currently used to expand our translational research program to other lysosomal storage disorders and to the development of other innovative therapies: stem cells (iPS cells and adult stem cells) for muscle and bone regeneration (regenerative medicine); lentiviral gene therapy via hematopoietic stem cell transplantation (as target for CNS related diseases), RNA based therapy (Antsense oligonucleotides to be used for splicing modulation) and has led to Collaborations on development of AAV gene therapy for MPS VI (European seventh framework program), In addition, innovative diagnostic tools are developed (e.g. biomarkers, splicing assay).

Our multidisciplinary clinical research programs focus on the collection and analysis of standardized clinical follow-up data, patient reported outcomes and biological materials (biobanks; metabolomics/genomics/transcriptomics). Within the field of Porphyrias our center was actively involved in the landmark trial that gave Afamelanotide marketing authorization for erytropoetic protoporphyria (EPP). Currently our center treats the largest number of patients with EPP in a single center worldwide.

Our center participates in the acute porphyria natural history study and participates in a phase 3 trial with ALN-AS1 an subcutaneously administered RNA interference (RNAi) for the treatment of recurrent acute porphyria.

There is a broad collaboration with both national and international partners, these include: LUMC Leiden, Nl (Prof. van der Maarel, Prof. Hoeben, Prof. Staal); MUMC Maastricht, Nl (Dr. Verdijk); MPI Munster, Germany (Prof Schoeler); Stanford School of Medicine, USA (Prof. Rando); Kumamoto University, Japan (Prof. Okumiya) and others.

Examples of funded collaborative clinical research of the center are:

  • MRI Studies on the function of the diaphragm a PhD project funded by de Prinses Beatrix Spierfonds which is performed in collaboration with the department of radiology

  • Patient reported outcome and validation of new outcome tools such as the RPAcT (Rotterdam Activity Scale) for Pompe disease. The tool has been validated for the UK, US and the Netherlands and is currently validated for Germany, France, Spain and Italy in collaboration with various centers across and partners of the European Pompe Consortium (EPOC). The tool has been licensed to various industries that are active in the field of development of next generation therapies for Pompe disease. This research is supported by a research support agreement obtained from the industry and TKI (topsectoren voor Kennis en Innovatie)

  • Long term neurological outcome in infants with Pompe disease, a PhD project funded by Prinses Beatrix Spierfonds. In this project the center collaborates with LUMC leiden and Radboud UMC.

  • Natural course Long term effects of enzyme therapy for Pompe disease, NCL, MPS II and VI, Mucilipidosis by ZonMw, Stofwisselkracht, research support agreement by the industry (Sanofi/Genzyme) and TKI (topsectoren voor Kennis en Innovatie). These are collaborative projects with many clinical and diagnostic departments and our research laboratory

Clinical Trials & Registries

  • AAV gene therapy –Funded by two consecutive programs of the seventh EU framework program (EUCLYD and MeuSix). This program is led by Fondazione Telethon and is collaborative project with Erasmus MC University and Hacettepe University in Ankara. The project has resulted in a phase I clinical study on AAV gene therapy which has started to enroll the first patients, we at Erasmus MC are in the final stage of the CCMO process and awaiting approvalParticipation in various international industry driven clinical trials for next generation therapies for Pompe disease (Biomarin, Amicus, Genzyme-Sanofi)Participation in various industry driven registries (Morquio, PKU, MPS II, MPS VI, Pompe disease)

Preclinical and translational research

  • Muscle on a chip (TKI), a collaborative project between LUMC Leiden en Erasmus MC University supported by Prinses Beatrix Spierfonds and TKI (topsectoren voor Kennis en Innovatie)

  • Regenerative Medicine – iPS cells, muscle stem cells (TexNet) and cartilage (PhD project funded by WeFoundation & Vriendeloterij)

  • Development of lentiviral gene therapy via hematopietic stem cells for Pompe disease (PhD project funded by SSWO) and Hunter disease (Hunter foundation), acollaborative project with LUMC Leiden (Hoeben & Staal) and Manchester (Bigger).

  • Development of Antisense oligonucleotides as a treatment for Pompe disease (Postdoc funded by SSWO)

Type of

Collaborations

a. Within Erasmus MC the Center for Lysosomal and Metabolic Diseases provides a structural collaboration between the departments- Pediatrics, Internal Medicine, Neurology, Hospital Pharmacy, Clinical Genetics. These centers work together and take joint responsibility for patients (children and adults) with lysosomal and other metabolic disorders. Delegates of these departments form the “indicatie commissie” with has been appointed by the Board of Directors and which was appointed to implement expenisve orphan drugs for several lysosomal storage disorders in the most sensible way. The “indicatie commissie” also evaluates outcomes of patients treated with expensive orphan drugs and plays a role in adaptation of inclusion and exclusion criteria for treatment of lysosmal storage disorders . The committee has an independent external chair (UMC Utrecht). Expensive orphan drugs – (weekly/biweekly) intravenous enzyme replacement therapy for Pompe disease, MPS I (Hurler/Scheie); MPS II (Hunter), MPS VI (Maroteaux-Lamy, Mannosidosis and intraventricular enzyme replacement therapy (biweekly) for NCL2 (Neuronal Ceroid Lipofucsinosis) are evaluated by the committee. For all of these diseases (except for MPS I) Erasmus MC is the single reference center in the Netherlands. For Pompe disease it is largest center of expertise worldwide. Over 5000 infusions for the aforementioned diseases are administered in hospital and at home under the supervision of the center.

b. Patient care is performed with a multidisciplinary team consisting of physicians (e.g. pediatricians and internists specialized in metabolic diseases), (child)neurologist, rehabilitation physician, clinical geneticists, cardiologists, pulmonologists, (orthopedic/neuro) surgeons, (research) nurses, physiotherapists, dieticians, (neuro)psychologists and social workers. The center targets the whole spectrum of metabolic diseases from birth to late adulthood and as such it collaborates with many departments and and ACEs of the Sophia Children’s Hospital and ErasmusMC in a broader sense. , both when it comes to patient care and research.

c. Examples of collaborations with other ACES are those with the pediatric thorax center and (adult) thorax center, department of radiology (MRI studies), plastic surgery (ACE for Congenital Anatomical Malformations) and ACE for Bone and Joint.

d. On the national level the Center it should be noted that the center also chairs the pediatric metabolic department in Leiden and thereby the center is responsible for the diagnosis, care and treatment of metabolic patients in LUMC Leiden. In addition, the center has a regional consultancy function for diagnosis, and treatment of patients with potential metabolic disorders in the South-West of The Netherlands (which covers about 4 million Dutch inhabitants). The center collaborates with many centers in the region. It also plays a role in neonatal screening for the region for 13 different metabolic disorders. The Gezondheidsraad and the Ministry of Health have recently decided that the neonatal screening program for metabolic diseases will be expanded to 24 metabolic diseases in the next years.

e. Another development is the recent formation of United for Metabolic Diseases. This a new collaboration between all metabolic centers in the Netherlands and Metakids (a public fund for research on metabolic diseases) in the field of research and patient care aimed at improving diagnosis, outcome and innovative treatment options for patients.

f. The International Collaborative activities of the center have also expanded over the years and include among others

g. - European Reference Networks: The center participates in the European Reference Network MetabERN and Euro-NMD. The chair of the Center for Lysosomal and Metabolic Diseases (Prof A.T. van der Ploeg) has been appointed as vice-coordinator of MetabERN. She is also also leader of the Lysosomal Storage Disorders (LSD) subnetwork of metabERN. The MetabNetwork and EuroNMD network meet on a regulare basis and there are monthly teleconferences for metabERN. The center will host the LSD subnetwork meeting in Rotterdam on November 3 2018.

h. - MetabERN and EuroNMD are among the largest European Reference Networks that have been formed. MetabERN represents 69 Healthcare Providers from 18 countries and EuroNMD 61 Healthcare Providers from 14 countries

i. - In the field of Pompe disease, the center (chair of the center) serves as co-chair of European Pompe Consortium. This network includes caregivers and researchers for 13 countries (EPOC).

j. - George Ruijter, head of the metabolic lab of the center and dept of clinical Genetics is chair of ERNDIM that has set up a validation and certification program for European Centers to improve metabolic diagnostics

k. - The head of the research lab (Pim Pijnappel) is treasurer of the ESGLD (European Study Group on Lysosomal Storage Disorders) a research collaborative

l. - For the porphyrias we collaborate internationally via the European Porphyria network (EPNET). Dr. J. Langendonk is treasurer of EPNET.In the field of Organic Acidurias and Urea Cycle defects the center plays an active role (Monique Williams) in EIMD (Study group of intoxication type of Inborn Errors of Metabolic Diosrders)

m. Research collaborations on the national and international level, include among others those with LUMC Leiden, NL (Prof. van der Maarel, Prof. Hoeben, Prof. Staal); MUMC Maastricht, NL (Dr. Verdijk); MPI Munster, Germany (Prof. Schoeler); Stanford School of Medicine, USA (Prof. Rando); Kumamoto University, Japan (Prof. Okumiya), TIGEM – Telethon Institute of Genetics and Medicine, Napels, Italy (Prof. Parenti, Prof. Auricchio), Genethon, Paris, France (Prof Frederico Mingozzi) and Institut de Myologie, Paris, France (Prof. Laforet), Universität Heidelberg, Germany (Prof. Kölker).

n. The center works closely together with patients organizations on the national and international level both when it comes to improvement of patient care and research. An example of a long lasting collaborative research activity is the IPA/Erasmus MC Pompe Survey. Since 2002 Pompe patients all over the world fill in an annual survey. Through these questionnaires we obtain better insight in the natural course of Pompe disease, Quality of Life and other PROMS (patient reported outcome measures) and effects of therapy.

Educational

Contributions

Within the ACE an educational program (bachelor and/or master) is in place for students medicine and molecular medicine, nursing and pediatric physiotherapy of the Erasmus University.

The center has 20 PhD and 1 MSc students with 5 nationalities (Colombia, China, Brasil, Spain, Italy, The Netherlands) who participate in different programs. These include the Molecular Medicine Master program (2 year, 120 ECTs; NVAO accreditation, top rated program by the Dutch Study Choice Guide;www.erasmusmc.nl/mscmolmed/). Netherlands Institute for Health Sciences (Nihes, (www.Nihes.com)) and Medical Genetics Centre South-West Netherlands (MGC; recognized by the Royal Academy of Arts and Sciences (KNAW), www.medgencentre.nl) program (30 ECTs per student in 4 years), and also follow several other innovative lecture series and advanced courses within the Erasmus MC.

The Centre provides education to internists, pediatricians, (child-)neurologists, clinical geneticists and neonatologists in training as well as post academic education to nurses and physicians. Basic science teaching involves: Molecular Medicine master program: lecturers, examiners, and course directors (30 students), supervisor literature studies (4 students); AIOS Clinical Genetics: lecturer diagnostics Pompe disease (15 specialists); Summerschool Junior Med: lecturer stem cells for 30 talented high school students; Minor Genetics in Society: lecturer on gene therapy and stem cells (15 students); Molecular Biology in Cardiovascular Research: lecturer stem cells in cardiovascular research (master program, 15 students). Several lectures in courses outside the Erasmus MC (Utrecht University).

The post academic education is both on a national (PAOG, Boerhaave, national medical specialist societies) as well as on an international level (e.g. international course on lysosomal storage disorders (Nierstein), Metabolic Myopathies, Recordati Rare Diseases Academy, Pompe Academy, International Pompe Expert Days. Evaluation of the educational activities vary from good to excellent (set-Q, DRECT and others). In October 2018 the center will organize the scientific meeting and general assembly of EPNET in Rotterdam.

In the 2019 the center will organize the SSIEM congress (Society for the Study of Inborn Errors of Metabolism) in Rotterdam (2-6 september). This congress will accomodate 3000 visitors (clinicians, basic scientists and students) in the field of metabolic diseases. The title of the Congress is "Building Bridges". and aims to share knowledge with other fields of interest and to bridge the gap between bench and bedside. The PI of the Center for Lysosomal and Metabolic Diseases will chair the Congress.

Patient

Care Activities

The treatment and clinical follow-up of patients with a metabolic disorder explicitly requires academic expertise (ROBIJN: 100% academic). The catchment area of the center covers metabolic care for approximately 25% of the total Dutch population (children and adults) and is thereby the largest metabolic center in the Netherlands. The center provides the metabolic care for both LUMC and Erasmus MC.

The center is the single national reference center for Pompe disease, MPS II and MPS VI and provides more than 5000 in hospital and home based enzyme replacement therapies on a yearly basis. Furthermore it is the single national reference center for the Porphyrias and the only center in the Netherlands that treats patients with EPP with afamelanotide. The center covers the patient care for the NFU and ministry of health recognized expert centers for rare diseases: Center for Lysosomal and Metabolic Diseases, the Pompe Center, Center for PKU, organic acidurias, and urea cycle disorders and the Netherlands Porphyria Center.

Recently we performed the first combined liver-kidney transplantations in the Netherlands in 2 adults with methylmalonic aciduria. As the role of liver transplantation for the treatment of organic acidurias is expanding we will perform more of these highly complex transplantations in the future, and aim to further optimize this care.

The center plays a leading role in European Reference Networks (ERNs). Multi-disciplinary care pathways and guidelines have been developed and will be kept at the at the highest up to date level to warrant optimal patient care and treatment of patients. In the oncoming years we aim to expand the number of 'care paths' following the principles of 'Value Based Health Care' with a special focus on outcome measurements and reporting of the results.

In line with our continuous efforts to improve the quality of care we aim to further develop unambiguous guidelines for optimal, individualized treatment regimens, in collaboration with international partners e.g. within the European Pompe Consortium (EPOC) , MetabERN and EuroNMD, and the European Porphyria Network (EPNET).

Patients are followed by IRB approved standardized clinical follow-up protocols and by patient reported outcome. Data are used to improve the quality of patient care, personalized medicine and define new possible targets for development of new therapies

The center participates in several industry driven clinical trials on innovative orphan drugs and is successful in performing translational research to find new therapeutic strategies The center and its departments have taken part in several audits such as NIAZ. It has received various audits on clinical trials including one of the FDA with very good results.

The center is currently making preparations to participate in a Phase I/II AAV gene therapy trial for MPS VI and is in the final stage of evaluation by CCMO and waiting for final approval (EU funded program).

Our research has led to the development and implementaion of aninnovative therapy in the past. The center has obtained various patents in the field of development of RNA based therapy and regenerative medicine (muscle stem cells) and explores the possibilities to implement and valorize the findings and

The chair of the center for lysosomal and metabolic diseases has been appointed as "kwartiermaker speerpunt Zeldzame Ziekten" which will be one of the four focus area's of the new Sophia Children's Hospital As such she collaborates with all departments/ACESof Thema Sophia. . In depth interviews have shown that all departments participating in Thema Sophia play an important role in the care of patients with rare diseases. A prolinminary inventory revelaed that the percentage of care for patients with rare diseases perfomed by the various departments of thema Sophia ranged from 40-100%.

Societal Relevance to Research, Education and Patient Care

Societal and/or economic valorization of knowledge, patents: The center has previously developed enzyme replacement therapy for Pompe disease (cloning of the GAA gene, generation of a knock-out mouse model; biotechnological production of GAA in milk of transgenic animals and Chinese Hamster Ovary Cells) and valorized this. In the last three years the center has generated new IP (patents) on innovative treatment strategies. Newly developed clinical assessment tools have been out licensed to various industries.

The center has been chosen as center of excellence by industrial partners. Our research of private public partnership has recently been acknowledged as innovative and granted by a TKI-LSH grant (Topconsortia for kennis en innovatie, life science and health). The center has been appointed by the ministry of health to implement costly orphan drugs in the most sensible way for several lysosomal storage disorders, including Pompe disease, MPS II and VI, as single center in the Netherlands. The societal relevance of the subject is reflected by the extensive attention in the media. With the Institute of Medical technology Assessment we work on cost effectiveness studies.

The center plays a key role in international consortia and European Reference Networks (metabERN, EuroNMD). The center is one of the drivers behind EPOC (European Pompe Consortium). This consortium has members of 11 European countries and among others generates international guidelines for start stop criteria of costly orphan drugs (enzyme replacement therapy). Education: We have recently contributed to the book: "Toegewijde dokters. Waarom de niet-medische competenties geen bijzaak zijn". This book is currently used as basis for courses/symposia.

The center performs teaching activities in various (inter)national courses and/or serves as organizer. The center has proven to be attractive for international colleagues, PhD and master students. Prevention: Neonatal screening programs on rare metabolic diseases has been expanded over the last years and the "Gezondheidsraad" has advised to further increase the number of Dutch screening programs for metabolic diseases from 14 to 27 in the next years. This will increase the number of referrals of the patients, who are selective referred by the RIVM to Academic Metabolic Centers. The center for Lysosomal and Metabolic Diseases at Erasmus MC is the largest metabolic center in the Netherlands and covers the metabolic care for approximately 25% of the Netherlands.

Viability of Research, Education and Patient Care

Our aim is to improve prospects of patients with metabolic diseases by providing state-of-the art clinical care, education and performing both clinically applied, translational, and basic research aimed at the development of innovative new therapies. This by a close collaboration of physicians, clinical biochemical geneticists and molecular cell biologists at both the senior and junior level. Weekly research meetings are held to discuss study results and future directions of research.

Within our ACE 20 PhD students with different backgrounds (e.g. medical, biochemical, biological) are working and being trained, several are international students (currently 3 international PhD students and 2 Master students) funded through exchange programs. Four senior staff members have been temporarily been employed in acknowledged international institutes (e.g. Max Planck Institute Munster, Stanford University, School of Medicine, Palo Alto).

Several staff members participate in young talent programs e.g. female career development program . The high standard of research performed in our ACE is reflected by our output: - 115 publications within the last 5 years in peer-reviewed journals of which 21.8% were in Q1 journals with 12.5% in the top 10% of the respective fields (including the New England Journal of Medicine, Nature, Neurology).

The staff of the center provides (key note) lectures on a regular basis at international scientific meetings. The center has been elected to organize the international Society for the Study of Inborn Errors of Metabolism ( SSIEM) congress 2019 with about 3000 participants. The center has keye positions in European Pompe Consortium (EPOC, initiator) and European Reference Networks (MetabERN and Euro-NMD) and EPNET.

Key and relevant publications of the last five years

  • Ebbink BJ, Poelman E, Plug I, Lequin MH, van Doorn PA, Aarsen FK, van der Ploeg AT, van den Hout JM. 2016. Cognitive decline in classic infantile Pompe disease: An underacknowledged challenge. Neurology. 2016 Mar 29;86(13):1260-1.
  • de Vries, JM, Esther Kuperus, E, Hoogeveen- Westerveld, M, Kroos, MA, Wens, SCA, Stok M, van der Beek, MD NAME, Kruijshaar, ME, Rizopoulos, D, van Doorn, PA, Van der Ploeg, AT, Pijnappel, WPPM Pompe disease in adulthood: Effects of antibody formation on enzyme, Genet Med 2016, in press
  • Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FP, Sijbrands EJ, de Rooij FW, Lebwohl M, Naik H, Goding CR, Wilson JH, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59.
  • Bergsma AJ, Kroos M, Hoogeveen-Westerveld M, Halley D, van der Ploeg AT, Pijnappel WW. 2015. Identification and Characterization of Aberrant GAA pre-mRNA Splicing in Pompe Disease Using a Generic Approach. Hum Mutat. 2015 Jan;36(1):57-68.
  • Pijnappel WW, Esch D, Baltissen MP, Wu G, Mischerikow N, Bergsma AJ, van der Wal E, Han DW, Bruch Hv, Moritz S, Lijnzaad P, Altelaar AF, Sameith K, Zaehres H, Heck AJ, Holstege FC, Schöler HR, Timmers HT. A central role for TFIID in the pluripotent transcription circuitry. Nature. 2013 Mar 28;495(7442):516-9.
  • van der Beek NAME, de Vries JM, Hagemans MLC, Hop WCJ, Kroos MA, Wokke JHJ, de Visser M, van Engelen BGM, Kuks JBM, van der Kooi AJ, Notermans NC, Faber CG, Verschuuren JJGM, Reuser AJJ, van der Ploeg AT, van Doorn PA. 2012. Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study. Orphanet J Rare Dis. 2012 Nov 12;7:88.
  • Kroos M, Hoogeveen-Westerveld M, Michelakakis H, Pomponio R, Van der Ploeg A, Halley D, Reuser A; GAA Database Consortium:, Augoustides-Savvopoulou P, Ausems M, Llona JB, Bautista Lorite J, van der Beek N, Bonafe L, Cuk M, D'Hooghe M, Engelen B, Farouk A, Fumic K, Garcia-Delgado E, Herzog A, Hurst J, Jones S, Kariminejad MH, Küçükçongar A, Lissens W, Lund A, Majoor-Krakauer D, Kumamoto S, Maravi E, Marie S, Mengel E, Mavridou I, Munteis Olivas E, Najmabadi H, Okumiya T, Peric S, Paschke E, Plecko B, Robberecht W, Serdaroglu P, Shboul M, Tansek MZ, Tarnutzer A, Stojanovic VR, Tylki-Szymanska A, Venâncio M, Verhoeven K. 2012. Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants. Hum Mutat. 2012 Aug;33(8):1161-5.
  • Ebbink BJ, Aarsen FK, van Gelder CM, van den Hout JMP, Weisglas-Kuperus N, Jacken J, Lequin MH, Arts WFM, van der Ploeg AT.. Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy. Neurology. 2012 May 8;78(19):1512-8.
  • van Til NP, Stok M, Aerts Kaya FS, de Waard MC, Farahbakhshian E, Visser TP, Kroos MA, Jacobs EH, Willart MA, van der Wegen P, Scholte BJ, Lambrecht BN, Duncker DJ, van der Ploeg AT, Reuser AJ, Verstegen MM, Wagemaker G. Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood. 2010 Jul 1;115(26):5329-37.
  • van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, Herson S, Kishnani PS, Laforet P, Lake SL, Lange DJ, Leshner RT, Mayhew JE, Morgan C, Nozaki K, Park DJ, Pestronk A, Rosenbloom B, Skrinar A, van Capelle CI, van der Beek NA, Wasserstein M, Zivkovic SA. A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Engl J Med. 2010 Apr 15;362(15):1396-406.
  • van der Ploeg AT. The Dilemma of Two Innovative Therapies for Spinal Muscular Atrophy. N. Engl J Med 2017 Nov 2;377(18):1786-1787
  • Kuperus E, Kruijshaar ME, Wens SCA, de Vries JM, Favejee MM, van der Meijden JC, Rizopoulos D, Brusse E, van Doorn PA, van der Ploeg AT, van der Beek NAME. Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study. Neurology. 2017 Dec 5;89(23):2365-2373.
  • Bergsma AJ, van der Wal E, Broeders M, van der Ploeg AT, Pijnappel WWM. Alternative Splicing in Genetic Diseases: Improved Diagnosis and Novel Treatment Options. Int Rev Cell Mol Biol. 2018;335:85-141. doi: 10.1016/bs.ircmb.2017.07.008. Epub 2017 Sep 12.

PhD theses of the last five years

  • Atze Bergsma: Pre-mRNA splicing: Prospects for antisense therapy, 20 september 2016
  • Stephan C.A. Wens, Neuromuscular Imaging and Phenotypical Variation in Pompe Disease. Erasmus Univeristy, 18 May 2016.
  • Carine I. van Capelle, Children with Pompe disease: clinical characteristics, peculiar features and effects of enzyme replacement therapy. Erasmus University, 18 June 2014.
  • Linda E.M. van den Berg, The Musculoskeletal System in Pompe Disease. Pathology consequences and treatment options. Erasmus University, 24 June 2014.
  • Juna M. de Vries, Natural Course, Effects of Enzyme Therapy and Prognostic Factors in Adults with Pompe Disease. Erasmus University, 10 June 2014.
  • Carin M. van Gelder, Enzyme- replacement therapy in classic infantile Pompe disease. Erasmus University, 11 December 2013.
  • Deniz Güngör, Survival, Quality of Life and Effects of enzyme replacement therapy in adults with Pompe disease. Outcomes of the IPA/Erasmus MC Pompe Survey. Erasmus University, 19 November 2013.
  • Merel Stok, Stem cell based gene therapy for Pompe’s Disease. Erasmus University, 22 October 2013.
  • Marion M.M.G. Brands, Enzyme-replacement therapy in mucopolysaccharidoses with a specific focus on MPS VI. Erasmus University, 15 October 2013.
  • Nadine A.M.E. van der Beek, Clinical features, disease course, and effects of enzyme therapy in Pompe disease, Erasmus University, 23 April 2013.
  • J. Chris van der Meijden, Pompe Disease in Children and Adults: Further Insights into the Clinical Presentation and Long-Term Effects of ERT : An example of sustainable data collection in rare diseases, 12 December 2017
  • B. Johanneke Ebbink, Long-term Neuropsychologic Outcome in Children Diagnosed with a Lysosomal Storage Disease, 14 November 2017
  • Tim A. Kanters, Health Technology Assessment Of Orphan Drugs : The example of Pompe disease, 8 December 2016
  • Qiushi Liang, A Step Forward: Lentiviral gene therapy as a cure for Pompe disease, 26 September 2017
  • Erik van der Wal, Modeling of Pompe Disease using Induced Pluripotent Stem Cells for the Development of Novel Therapies, 12 October 2017
  • Esther Poelman, Classic infantile Pompe disease: Effects of dosing and immunomodulation on long-term outcome, 12 December 2018
  • Esther Kuperus, Effects of long-term enzyme-replacement therapy and modifying factors in adults with Pompe Disease, 20 November 2018
  • Esmee Oussoren, Study on bone and cartilage disease in Mucopolysaccharidoses and Mucolipidoses, 4 December 2018

Non-scientific publications related to the ACE

Principal coordinator(s)