Trials and treatments developed with our support 

AFM-Telethon has supported and continues to support the development (clinical trials underway or in preparation) of over forty drugs in gene therapy, cell therapy and pharmacology. Almost half of them concern neuromuscular diseases, the other concern rare diseases. 

Some are already available for patients, and others are still in development. 

Table of drugs developed with the support of AFM-Telethon

• Cuprior® (trientane tetrahydrochloride), a copper chelator for Wilson’s disease. 
• Firdapse® (3,4-diaminopyridine) for Lambert-Eaton syndrome. 
• Lumevoq® (gene therapy) for Leber Hereditary Optic Neuropathy. 
• Namuscla® (mexiletine) for myotonic syndromes (dystrophic and non-dystrophic). 
• Metformin (N,N-dimethyl-biguanide) for Steinert myotonic dystrophy. 
• Skysona® (gene therapy) for adrenoleukodystrophy. 
• Strimvelis® (gene therapy of the bone marrow stem cells) for X-linked severe combined immune deficiency. 
• Zynteglo® (gene therapy of the bone marrow stem cells) for beta thalassemia. 
• Zolgensma® (onasemnogene abeparvovec: first gene therapy treatment derived partly from research conducted at Genethon) for spinal muscular atrophy linked to SMN1.  

In 2023, AFM-Telethon is supporting 39 trials underway or in preparation in 30 rare diseases. 

Rare autoimmune disease 

• Systemic lupus erythematosus. A phase I/II trial by allogeneic mesenchymal stem cells for patients with systemic lupus erythematosus with kidney damage resistant to traditional treatments is underway. Find out more. 

Rare diseases of the brain and nervous system 

• Multiple sclerosis. A pilot phase I clinical trial to assess the effects of cell therapy using autologous Epstein-Barr virus-specific cytotoxic T-lymphocytes in individuals presenting for the first time signs of multiple sclerosis is underway. Find out more. 
• Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease :
  • Two gene therapy treatments, one for forms related to mutations of superoxide dismutase 1 (SOD 1), and the other for forms related to the C9ORF72 gene, are currently being developed (preclinical development). 
  • A phase IIB trials, the MIROCALS trials, assessed the effects of interleukin-2 at low dose, including on biomarkers to be identified. 
• Phelan-McDermid syndrome: Molecule screening on human motor neurons produced from pluripotent stem cells helped identify the therapeutic potential of lithium in this genetic form of autism. A phase I/II trial is underway in France (Professor Richard Delorme - Robert Debré hospital in Paris), to assess the effect of lithium in this rare genetic form of autism.
• Wolfram syndrome.A phase II valproic acid trial began at the end of 2021. Find out more. 

Rare disease of the liver 

• Crigler-Najjar syndrome.A phase I/II gene therapy trial with an AAV vector carrying a normal copy of the relevant gene is underway. Find out more. 

Diseases of the muscle 

Duchenne muscular dystrophy 

• Gene therapy trial to assess a microdystrophin (abbreviated version of the Duchenne muscular dystrophy gene) associated with an AVV vector. The trial is currently recruiting. It takes place in several investigative centers in France, as well as in the United Kingdom, the United States and Israel. This innovative gene therapy product is the result of research conducted by Genethon, the laboratory of the AFM-Telethon, in collaboration with the team of Prof. George Dickson (University of London) and the Nantes-based team of Caroline Le Guiner (gene therapy laboratory, CHU/Inserm). Find out more. 
• A natural history study without gene therapy treatment is a prerequisite to the microdystrophin gene therapy trial: this trial is currently recruiting. 
• The preclinical development of a gene therapy by another type of candidate drug (morpholino antisense oligonucleotides) for the exon 53 skipping enable the launch of a phase I/II human clinical trial, the SRP-4053 trial (Skip-NMD) whose results have been published. 
• Phase III tamoxifen trial. This drug, used in oncology for almost 40 years, is assessed in Duchenne muscular dystrophy, following preclinical studies supported by the AFM-Telethon. A phase III clinical trial underway, the TAMDMD trial, in France, Germany, Spain, the Netherlands and the United Kingdom. Find out more. 
• Phase III pharmacological trial to assess nebivolol, a drug used to treat high blood pressure, and assessed for prevention of heart attack in Duchenne muscular dystrophy. The results of the trial are being analyzed.
• Phase Ib pharmacological open trial to assess rimeporide, a molecule initially developed to treat chronic heart failure finished. Results published. Find out more. 
• A preclinical development of a pediatric form of a molecule to combat muscular atrophy, BIO 101 or Sarconeos, is underway, prior to a clinical trial that could start in 2020, depending on regulatory authorizations. Find out more. 

Limb girdle muscular dystrophy 

• Calpain-related R1 limb girdle muscular dystrophy (ex-LGMD2A) or calpainopathy. The preclinical development of an AAV vector carrying a normal copy of the CAPN3 gene for use in gene therapy is underway at Genethon. Find out more. 
• Alpha-sarcoglycan-related R3 limb girdle muscular dystrophy (ex-LGMD2D) or Alpha-sarcoglycanopathy. A preclinical study aims to assess the effects of givinostat in an animal model prior to a potential human clinical trial. This molecule, by acting on follistatin, promotes increased muscle mass and limits fibrosis and inflammation of the muscle. 
• Gamma-sarcoglycan-related R5 limb girdle muscular dystrophy (ex-LGMD2C) or Gamma-sarcoglycanopathy :
  • The preclinical development of an AAV vector carrying a normal copy of the SGCG gene (gene therapy) us underway at Genethon. Find out more.
  • Preclinical studies to assess the effects of givinostat in an animal model prior to a potential human clinical trial. Givinostat acts via the follistatin gene by limiting fibrosis and inflammation of the muscle and promoting muscle regeneration,  
• FKRP-related R9 limb girdle muscular dystrophy (ex-LGMD2I). Genethon developped a gene therapy using an AAV vector carrying a normal copy of the FKRP gene. A natural history study of this form of LGMD is underway. In 2022, it was granted authorization to start a phaseI/II gene therapy clinical trial in France, Denmark and the UK.

Charcot-Marie-Tooth disease 

• Preclinical studies of PTX3003 enabled performance of a phase II trial whose results were published in December 2014. Following this trial, a European phase II trial began in December 2015 and received an open-label extension.  
• Prior to a clinical trial to assess the effects of IFB-088 (sephin 1) in Charcot-Marie-Tooth disease, a Phase I clinical trial in healthy volunteers assessed the safety and tolerance of IFB-088 in humans, with the first results already announced. 

Other rare diseases of the muscle 

• Spinal muscular atrophy with progressive myoclonic epilepsy. A preclinical development of a gene therapy using an AAV vector carrying a normal copy of the ASAH1 gene has begun. 
• Oculopharyngeal muscular dystrophy (OPMD). A phase II cell therapy trial, now completed, assessed the effectiveness of a myoblast transplant on the pharyngeal function. Find out more. 
• Steinert myotonic dystrophy. A preclinical development aims to develop a gene therapy with an AAV-MBNL∆. 
• Pompe disease or type-II glycogenosis.  Genethon and the company Spark Therapeutics have developed a gene therapy that targets the liver and uses an AAV vector carrying a normal copy of the GAA gene, SPK-3006. A phase I/II trial, the RESOLUTE trial, aiming to assess the tolerance and effectiveness of different doses of SPK-3006 has begun in the United States. 
• Myotubular myopathy.  A phase I/II gene therapy trial to assess the use of an AAV vector carrying a normal copy of the MTM gene. This gene therapy was initially designed at Genethon.
• Centronuclear myopathies.A phase I/II gene therapy trial assesses dynamin 101 (DYN101), an antisense oligonucleotide in congenital myopathies related to the DNM2 or MTM1 gene.
• Sarcopenia. A preclinical development aims to produce a recombinant growth factor (recGDF5) to offset the effects of muscle loss. 

Rare diseases of the skin 

• Dystrophic epidermolysis bullosa. A phase I/II trial with genetically-modified autologous skin cells is underway. 
• Junctional epidermolysis bullosa. A pilot study with genetically-modified autologous skin cells is underway. 
• Sickle-cell disease skin ulcers. The preclinical development of cell therapy at I-Stem aims to reconstruct the epidermal layers using substitutes obtained from embryonic stem cells.  

Rare disease of the blood 

• Fanconi syndrome. This phase I/II gene therapy trial involves restoring the activity of the Fanc-A gene (65% of patients) via gene transfer using a regulated lentiviral vector. Find out more. 
• Sickle-cell disease. This phase I/II gene therapy trial assesses the harmlessness and effectiveness of transplanting the patient’s own CD34+ cells modified by gene therapy. Find out more. 

Rare diseases of the immune system 

• Artemis deficiency. The preclinical development of a gene therapy product aims to express the Artemis gene at effective levels in the immune system (production of T and B lymphocytes). 
• X-linked severe combined immunodeficiency. A gene therapy product aiming to restore proper function of immune cells by expressing an optimized form of the IL2RG gene in the stem cells and the immune system is being evaluated as part of a phase I/II trial. 
• X-linked chronic septic granulomatosis. A phase I/II gene therapy trial aiming to restore the activity of a defective enzyme in the white blood cells, NAPDH oxidase, by gene transfer using a lentiviral vector. Find out more. 
• Wiskott-Aldrich syndrome.A phase I/II gene therapy trial treated 10 patients by ex-vivo gene transfer using a lentiviral vector inserted into the hematopoietic stem cells. Long-term safety and efficacy results were published in 2022. 

Rare diseases of the vision 

• Retinitis pigmentosa. A phase I/II cell therapy trial is underway to assess the repair of retinal tissue by cells of the retinal pigment epithelium derived from stem cells. Find out more. 
• Retinitis pigmentosa. The preclinical development of a gene therapy product (AAV-RdCVF) aims to improve vision in diseases of the retina. Find out more.