M. Cucchiarini (Homburg/Saar, DE)

Saarland University Medical Center Center of Experimental Orthopaedics
Dr. Magali Cucchiarini; PhD; is an Associate Professor; Group Leader; and Vice-Director of the Center of Experimental Orthopaedics; Saarland University Medical Center; Homburg/Saar; Germany. She graduated from the University of Nice-Sophia Antipolis; Nice; France in 1992 (Biochemistry and Pharmacology) and received her PhD Thesis with summa cum laude from this University in 1995 (Virology and Molecular Biology). Before joining the Saarland University; Dr. Cucchiarini was a senior post-doctoral fellow for three years at Harvard (Harvard Institutes of Medicine); Boston; MA in the field of anti-HIV gene therapy. Prior to moving to the USA; she worked for two years at the University Hospital Inselsspital; Bern Switzerland on HCV immunology and vaccination at the Department of Internal Medicine. Dr. Cucchiarini’s major research interest lies in generating novel cell-; gene-; and tissue engineered-based systems to treat orthopaedic disorders of the cartilage; bone; meniscus; tendons; and ligaments; with a focus on using the clinically relevant recombinant adeno-associated viral (rAAV) gene therapy vectors. Dr. Cucchiarini made over 138 national and international presentations; co-authored 13 books chapters and edited one book (Regenerative therapy for the musculoskeletal system using recombinant adeno-associated viral vectors); and is an author of over 150 peer-reviewed articles. Dr. Cucchiarini sits on the Editorial Boards for OAC Open; Journal of Experimental Orthopaedics; BioMed Research International; Orthopedic Journal of Sports Medicine; Current Pharmaceutical Design; Journal of Rheumatology and Orthopaedics; and Journal of Organ Biology. She also serves as a reviewer for Acta Biomaterialia; American Journal of Sports Medicine; Arthritis & Rheumatology; Arthritis Research and Therapy; Biomaterials; Clinical Epigenetics; Current Gene Therapy; Current Pharmaceutical Biotechnology; Current Pharmaceutical Design; Current Stem Cell Research and Therapy; European Cells and Materials; Experimental Cell Research; Expert Opinion on Biological Therapy; Gene Therapy; International Journal of Molecular Sciences; Journal of Gene Medicine; Journal of Molecular Medicine; Journal of Orthopaedic Research; Molecular Medicine; Molecular Therapy; Nanomedicine; Osteoarthritis Cartilage; PLoS One; Regenerative Medicine; Scientific Reports; Stem Cell Research & Therapy; Stem Cells International; Tissue Engineering. She serves as a Board Member of the Orthopaedic Research Society (ORS) and is involved at the ICRS and American Society of Gene & Cell Therapy (ASGCT).

Presenter Of 1 Presentation

Extended Abstract (for invited Faculty only) Cartilage and Meniscus

15.2.4 - Biomaterial-Guided Clinical Gene Therapy

Presentation Topic
Cartilage and Meniscus
Date
14.04.2022
Lecture Time
10:30 - 10:45
Room
Bellevue
Session Type
Special Session
Disclosure
No Significant Commercial Relationship

Abstract

Introduction

Lesions in the adult articular cartilage are prevalent, unsolved problems in clinical orthopaedics and they may lead to osteoarthritis if left untreated in affected patients. A variety of therapeutic options are available to manage sites of articular cartilage damage in the clinics but thus far, none are capable of reliably and permanently regenerating the original hyaline cartilage in cartilage defects with its full structural and mechanical integrity. Gene therapy is an attractive tool to durably enhance the processes of tissue repair in cartilage lesions over extended periods of time based on the administration of (chondro)reparative gene candidates in sites of cartilage damage. Gene transfer vehicles derived from the replication-defective human adeno-associated virus (AAV), in the form of genetically manipulated, gutless recombinant AAV (rAAV) vectors (1), are particularly well adapted shuttles to deliver a number of therapeutic genes capable of enhancing cartilage repair in translational settings, including sequences coding for growth, transcription, and signaling factors. However, this therapeutic strategy still faces critical challenges in applications in vivo due to the presence of numerous obstacles potentially impeding effective and durable gene transfer. These limitations include the presence of physical barriers (synovial fluid), of biological barriers (inflammatory mediators), of neutralizing compounds (pre-existing humoral responses against viral capsids and vectors), and the undesirable dissemination of the vectors to non-target sites. Clinical application of gene transfer vectors via controlled vector delivery approaches upon vector coating or encapsulation in biocompatible hydrogel, solid, or hybrid scaffolds (biomaterial-guided clinical gene therapy) is a valuable concept to support the persistent and localized release of the gene treatments in a spatiotemporally precise manner. Such a system may restrict gene vector dissemination, augment its temporal availability, prevent the loss of the therapeutic gene product, and protect viral vector capsids from neutralization (1-3). This innovative experimental procedure, showing a strong potential for cartilage repair and perifocal osteoarthritis protection in vivo (4,5), may be safely adapted to clinical applications in patients in a close future.

Content

Lesions in the adult articular cartilage are prevalent, unsolved problems in clinical orthopaedics and they may lead to osteoarthritis if left untreated in affected patients. A variety of therapeutic options are available to manage sites of articular cartilage damage in the clinics but thus far, none are capable of reliably and permanently regenerating the original hyaline cartilage in cartilage defects with its full structural and mechanical integrity. Gene therapy is an attractive tool to durably enhance the processes of tissue repair in cartilage lesions over extended periods of time based on the administration of (chondro)reparative gene candidates in sites of cartilage damage. Gene transfer vehicles derived from the replication-defective human adeno-associated virus (AAV), in the form of genetically manipulated, gutless recombinant AAV (rAAV) vectors (1), are particularly well adapted shuttles to deliver a number of therapeutic genes capable of enhancing cartilage repair in translational settings, including sequences coding for growth, transcription, and signaling factors. However, this therapeutic strategy still faces critical challenges in applications in vivo due to the presence of numerous obstacles potentially impeding effective and durable gene transfer. These limitations include the presence of physical barriers (synovial fluid), of biological barriers (inflammatory mediators), of neutralizing compounds (pre-existing humoral responses against viral capsids and vectors), and the undesirable dissemination of the vectors to non-target sites. Clinical application of gene transfer vectors via controlled vector delivery approaches upon vector coating or encapsulation in biocompatible hydrogel, solid, or hybrid scaffolds (biomaterial-guided clinical gene therapy) is a valuable concept to support the persistent and localized release of the gene treatments in a spatiotemporally precise manner. Such a system may restrict gene vector dissemination, augment its temporal availability, prevent the loss of the therapeutic gene product, and protect viral vector capsids from neutralization (1-3). This innovative experimental procedure, showing a strong potential for cartilage repair and perifocal osteoarthritis protection in vivo (4,5), may be safely adapted to clinical applications in patients in a close future.

References

1. Cucchiarini M. Human gene therapy: novel approaches to improve the current gene delivery systems. Discov Med 2016;21:495-506.

2 . Rey-Rico A, Cucchiarini M. Controlled release strategies for rAAV-mediated gene delivery. Acta Biomater 2016;29:1-10.

3. Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat Rev Rheumatol 2019;15:18-29.

4. Madry H, Gao L, Rey-Rico A, Venkatesan JK, Müller-Brandt K, Cai X, Goebel L, Schmitt G, Speicher-Mentges S, Zurakowski D, Menger MD, Laschke MW, Cucchiarini M. Thermosensitive hydrogel based on PEO-PPO-PEO poloxamers for a controlled in situ release of recombinant adeno-associated viral vectors for effective gene therapy of cartilage defects. Adv Mater 2020;32:e1906508.

5. Maihöfer J, Madry H, Rey-Rico A, Venkatesan JK, Goebel L, Schmitt G, Speicher-Mentges S, Cai X, Meng W, Zurakowski D, Menger MD, Laschke MW, Cucchiarini M. Hydrogel-guided, rAAV-mediated IGF-I overexpression enables long-term cartilage repair and protection against perifocal osteoarthritis in a large-animal full-thickness chondral defect model at one year in vivo. Adv Mater 2021;33:e2008451.

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Moderator Of 1 Session

Potsdam 1 Plenary Session
Session Type
Plenary Session
Date
12.04.2022
Time
13:15 - 14:15
Room
Potsdam 1
Session Description
Worldwide experts present the current therapeutic regimens and the future options to achieve effective cartilage repair
CME Evaluation

Meeting Participant Of

Glienicke Board Room (18) ICRS Committee Meeting

Scientific Programme Committee Meeting

Session Type
ICRS Committee Meeting
Date
14.04.2022
Time
10:45 - 11:30
Room
Glienicke Board Room (18)