Genethon’s teams present their progress at the ASGCT meeting

Limb girdle muscular dystrophies, rare diseases of the liver or production of vectors on a large scale: these are some of the topics presented by Genethon’s teams at the annual meeting of the American Society for Gene and Cell Therapy (ASGCT), to be held virtually from May 11 to 14.

ASGCT: Genethon’s oral presentations

• Giuseppe Ronzitti, manager of the “Liver gene transfer and immune tolerance” laboratory, will present results concerning X-linked hypophosphatemia. This disease is characterized by excessive loss of phosphate in the urine, leading to disorders of the skeleton, muscles and teeth.

Giuseppe Ronzitti’s team managed to demonstrate in mouse models that the use of targeted AAV gene therapy on the liver, inhibiting a signaling pathway for the FGF23 protein involved in this pathology, reduced problems in the bone, after a single injection.

AAV Liver Gene Therapy-Mediated Inhibition of FGF23 Signaling as a Therapeutic Strategy for X-linked Hypophosphatemia

When? Tuesday May 11 at 6.15 PM (US Eastern Time)

• Isabelle Richard, Head of the Progressive Muscular Dystrophies Laboratory, will present results of research in limb girdle muscular dystrophy LGMD-R9.

This disease is caused by anomalies in the gene coding the FKRP protein. This FKRP protein contributes to the stability and resistance of the muscle fibers. Isabelle Richard’s team managed to demonstrate the effectiveness of a gene therapy treatment, using an AAV vector to provide the non-mutated FKRP gene.  The treatment is effective at reduced doses, in relation to those used for other neuromuscular diseases. These promising results will be useful in establishing the doses to be used in upcoming trials.

Unprecedented Low Dose of AAV-Mediated Gene Transfer Corrects the Pathology in a Model for Fukutin-Related-Protein Deficiencies

When? Friday May 14 at 1:00pm (US Eastern time)

• Anne Galy, head of the Immunology and Biotherapies laboratory, and Patrick Santambien, Technological Development Director, will hold an “Education” session to discuss the scientific and technological challenges related to large-scale production of AAV and lentiviral vectors.

Large scale production of AAV and lentiviral vectors

When? Thursday May 13 at 10:00am (US Eastern time)

ASGCT: Genethon’s posters

• Gaelle Chauveau, from the Immunology and Biotherapies team, supervised by Sylvain Fisson, will present a poster detailing a new antigen-specific immunosuppression strategy, aiming to mitigate the inflammatory response triggered by certain ocular gene therapy treatments with AAV in the context of hereditary retinal pathologies.

Sub-retinal injection of AAV causes an inflammatory response, in a dose-dependent manner, that could lead to activation of T-cells specific to the transgene and/or the AAV vector. This immune response is suspected to be detrimental in certain clinical trials. The team managed to demonstrate that by injecting the AAV vector under the retina and peptides from the transgene at the same time, the immune response can be controlled, without the many side effects of non-specific immunosuppressing drugs that are traditionally used in a clinical setting.

Systemic Anti-Transgene T-Cell Immune Response Induced by Subretinal AAV Gene Transfer Can Be Inhibited by a Simultaneous Co-Injection of Peptides from the Transgene Product in Pathophysiological Conditions

When? Tuesday May 11 at 8 AM (US eastern time)

• Louisa Jauze, post-doctoral fellow in the “Liver gene transfer and immune tolerance” laboratory, will present a poster on her research to improve the effectiveness of gene therapy in hepatic glycogen storage diseases.

To increase the effect of gene therapy, she compares the effectiveness of two promoters, that aim to help the gene express itself in the hepatocytes affected by the disease.

Liver-Directed AAV Gene Transfer for Glycogen Storage Disease Type IA

When? Tuesday May 11 at 8:00am (USA Eastern time)

ASGCT: Genethon’s contributions

Several projects to which Genethon employees have contributed will also be presented.

• Novel Lentiviral Vectors for Gene Therapy of Sickle Cell Disease Combining Gene Addition and Gene Silencing Strategies

When? Tuesday May 11 at 8:00am (USA Eastern time)

• Transplantation of CRISPR/Cas9 Corrected Hematopoietic Stem and Progenitor Cells into a Mouse Model of Friedreich’s Ataxia

When? Tuesday May 11 at 8:00am (USA Eastern time)

• Follow-Up of a Phase I/II Gene Therapy Trial in Patients with Fanconi Anemia, Subtype A

When? Friday May 14 at 1:00pm (USA Eastern time)