Genethon Presents Significant Advances in Gene Therapy at European Society for Gene and Cell Therapy, Oct 19-22, 2021

Genethon’s R&D will be featured in 6 oral presentations and 10 e-posters at the virtual conference.

PARIS, FRANCE (October 18, 2021) – Genethon, a unique non-profit gene therapy R&D organization founded by the French Muscular Dystrophy Association (AFM-Telethon), announced today its researchers will report significant advances in gene therapy at the 28th International Congress of the European Society for Gene and Cell Therapy (ESGCT). The conference, which is virtual October 19-22, 2021, brings together thousands of scientists, clinicians and industry executives from across the globe.

“The extent of our participation in this global conference reflects the enormous progress Genethon is making in bringing gene therapies to patients suffering from rare  diseases,” said Frederic Revah, Genethon CEO. “Our scientists will be presenting some of the most significant advances to date in the field of gene therapy.”

The accomplishments of Genethon, which has pioneered the development of gene therapy for 30 years, will be featured in six oral presentations and in 10 e-posters depicting innovative technologies and therapeutics.

At ESGCT on Wednesday October 20th

Gene editing – Aboud Sakkal, a doctoral student at Genethon; “MMEJ-mediated IDLV knock-in via CRISPR/Cas9 in human hematopoietic stem/progenitor cells.” His work on correcting genetic dysfunction uses CRISPR technology combined with a modified lentivirus to target all cell types, including muscle and nerve cells which have little or no capability to regenerate. Tests on cell lines to treat hemophilia B, immune deficiency (X-SCID) and on hematopoietic cells demonstrated efficacy.

Muscle diseases – Isabelle Richard, Ph.D., head of the progressive muscular dystrophies team at Généthon and CNRS research director; “Gene replacement therapy in LGMD-R1.” Dr. Richard will demonstrate the effectiveness of gene therapy in an animal model of calpaïnopathy, one of the most frequent forms of limb-girdle muscular dystrophy.

Muscle diseases – Fanny Collaud, Ph.D., researcher on the immunology and liver diseases team at Genethon; “Artificial miRNA-mediated glycogen synthase silencing as effective substrate reduction therapy in glycogen storage diseases mouse models.” Dr. Collaud will present a gene therapy strategy adopted to fight the accumulation of glycogen in the muscles in two forms of glycogenosis, Pompe disease and Cori disease. Rather than expressing the missing enzyme (GAA for Pompe disease and GDE for Cori disease), the researchers regulated, with an AAV combined with a microRNA, the expression of the enzyme responsible for the synthesis of glycogen (GYS1) in muscles.

At ESGCT on Thursday October 21st

Gene editing – Mario Amendola, Ph.D., head of the gene editing team at Genethon, will chair a session dedicated to genome editing and gene therapy approaches to treating rare genetic diseases in vivo and ex vivo.

At ESGCT on Friday October 22nd

Metabolic and liver diseases

Dr. Lorenzo D’Antiga, one of the investigators working on the study at the Pope John XXIII Hospital in Bergamo, Italy, will share results observed in the last three patients treated. These results suggest that in patients with Crigler Najjar syndrome, GNT0003 at the dose of 5×1012 vg/kg is safe and restores UGT1A1 expression to levels allowing safe phototherapy withdrawal.

Louisa Jauze, a doctoral student on the immunology and liver diseases team at Genethon; “Overcoming anti-AAV pre-existing immunity to achieve safe and efficient gene transfer in clinical settings.” Ms. Jauze will present the results of work carried out for the development of a gene therapy treatment for Von Gierke disease (type 1A glycogenosis). The disease, which affects the liver and kidneys and causes severe hypoglycemia and tumors, is linked to the lack of expression (weak or completely absent) of the enzyme glucose-6-phosphasate. The researchers corrected this dysfunction in mice models of the disease with an AAV vector. The team is now working on optimizing the products for more efficiency with a view to entering the clinical phase.

Immunology and AAV Giuseppe Ronzitti, Ph.D., head of the immunology and liver diseases team at Genethon; “Overcoming anti-AAV pre-existing immunity to achieve safe and efficient gene transfer in clinical settings.” Dr. Ronzitti will present two studies on the immune response linked to AAV. As part of a collaboration with the Cure CN network, Dr. Ronzitti and his team have succeeded in using the enzyme, IdeS, to inhibit, in animal models, the immune response against AAV present in the context of natural or follow-on gene therapy. This significant and promising breakthrough can improve the effectiveness of gene therapy and expand the number of patients with access to it.