What we do
About our project
Lentiviral gene therapy involves the ex vivo engineering of hematopoietic stem and progenitor cells to reintroduce the genetic information needed to produce a specific protein that is missing in a given disorder.
This strategy has been used in the clinic and has shown efficacy for several indications over the past decades. We have developed this approach preclinically for Pompe disease and Hunter disease, and we are now moving it into the clinic.
For these developments, we have used modified lentiviral vectors with enhanced targeting of muscle and brain, the key tissues affected in Pompe disease and Hunter disease.
We are progressing to clinical studies for both disorders, starting with Pompe disease, and we are expanding these approaches for the treatment of CLN2 and CLN3.
Another major challenge in the field is the commercialization of such therapies. Even when preclinical and sometimes clinical research demonstrates strong efficacy, these therapies often fail to reach patients for profit-related reasons: if the disease is very rare, companies may judge the program to be commercially non-viable. As a result, effective therapies may never reach patients. To address this, we have founded Lenticure, a non-profit company 100% owned by Erasmus MC, which aims to develop and commercialize these therapies without a profit-driven business model.
Our research focus
For Pompe disease, we have developed next-generation lentiviral vectors expressing codon-optimized, IGF2-tagged acid α-glucosidase (GAA), which enhance uptake via the mannose-6-phosphate/IGF2 receptor. In murine models, these approaches correct glycogen storage, normalize the skeletal muscle proteome, and induce robust immune tolerance to GAA, supporting further clinical development. For Hunter syndrome, we are applying similar stem cell–based lentiviral strategies to achieve durable systemic enzyme delivery. Overall, our aim is to translate these stem cell gene therapies into safe, one-time treatments for patients with rare neuromuscular and metabolic diseases.
Funds & Grants
Our gene therapy program has obtained funding from the Prinses Beatrix Spierfonds, The Sophia Foundation, Metakids, Hersenstichting, Dioraphte, Health Holland, For Wishdom Foundation, Finding a Cure For Hunter Disease, StichtingZiekte van Pompe, Erasmus Foundation, ZonMW-NWA, Bobby & Robine Foundation.
Collaborations
Internal Collaboration
We collaborate with clinicians from Pediatrics (Dr. Hannerieke van den Hout, Dr. Esmee Oussoren, Dr. Hidde Huidekoper), and Neurology (Dr. Nadine van der Beek), with the Hospital Pharmacy (Dr. Sofieke de Wilde), with the genomics facility of the Erasmus MC
External Collaboration
We are part of United for Metabolic Diseases (UMD), the National Consortium for clinicians and scientist on metabolic diseases.
We collaborate with LUMC for clinical development of gene therapy (Prof. Frank Staal, Dr. Karin Pike-Overzet, Prof. Arjan Lankester), with Hannover Medical School for genotoxicity assays (Dr. Michael Rothe. Prof. Axel Schambach).
We collaborate with LentiCure for clinical development of lentiviral gene therapy for Pompe disease. Prof Pijnappel is unpaid Chief Scientifc Officer of LentiCure.
We are part of the European Pompe Consortium (EPOC).
Publications
Domain-substituted IGF2 tag modulates targeting of lentiviral gene therapy for Hunter syndrome. Catalano F, Stevic D, Zundo G, Huizer TF, Dammou Z, Vlaar EC, Katsavelis D, van den Bosch JC, van den Hout HJMP, Oussoren E, van der Ploeg AT, Ruijter GJG, Schaaf G, Pijnappel WWM. (2025) EMBO Molecular Medicine. 17. 11. 3197–3226.
Lentiviral gene therapy with IGF2-tagged GAA normalizes the skeletal muscle proteome in murine Pompe disease.Liang Q, Vlaar EC, Pijnenburg JM, Rijkers E, Demmers JAA, Vulto AG, van der Ploeg AT, van Til NP, Pijnappel WWMP. (2024) Journal of Proteomics. 291. 105037.
Lentiviral Gene Therapy for Mucopolysaccharidosis II with Tagged Iduronate 2-Sulfatase Prevents Life-Threatening Pathology in Peripheral Tissues But Fails to Correct Cartilage.Catalano F, Vlaar EC, Dammou Z, Katsavelis D, Huizer TF, Zundo G, Hoogeveen-Westerveld M, Oussoren E, van den Hout HJMP, Schaaf G, Pike-Overzet K, Staal FJT, van der Ploeg AT, Pijnappel WWMP. (2024) Human Gene Therapy. 35. Issues 7–8. Pages 256–268.
Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II. Catalano F, Vlaar EC, Katsavelis D, Dammou Z, Huizer TF, van den Bosch JC, Hoogeveen-Westerveld M, van den Hout HJMP, Oussoren E, Ruijter GJG, Schaaf G, Pike-Overzet K, Staal FJT, van der Ploeg AT, Pijnappel WWMP. (2023) Molecular Therapy – Methods & Clinical Development. 31. Article 101149.
IGF2-tagging of GAA promotes full correction of murine Pompe disease at a clinically relevant dosage of lentiviral gene therapy. Liang Q, Catalano F, Vlaar EC, Pijnenburg JM, Stok M, van Helsdingen Y, Vulto AG, van der Ploeg AT, van Til NP, Pijnappel WWMP. (2022) Molecular Therapy – Methods & Clinical Development. 27. Pages 109–130.
Lentiviral gene therapy prevents anti-human acid α-glucosidase antibody formation in murine Pompe disease.* Liang Q, Vlaar EC, Catalano F, Pijnenburg JM, Stok M, van Helsdingen Y, Vulto AG, Unger WWJ, van der Ploeg AT, Pijnappel WWMP, van Til NP. (2022) Molecular Therapy – Methods & Clinical Development. 25. Pages 520–532.
Our team
Prof. Pim Pijnappel, PhD
Fabio Catalano, PhD
Gerben Schaaf, PhD
Giacomo Zundo, MSc
Tessa Huizer, BSc
Dejan Stevic, MSc
Max Hennink, MSc
Miro Weitzel, MSc
Wassim Ouhammou, BSc
Tess van der Loo, MSc
