For 30 years, ELA has been accelerating research on leukodystrophies. Thirty years ago, researchers first learned about these diseases in order to consider long-awaited therapeutic options. Today research has entered the phase of clinical trials and the very first therapies have been authorized. The hope is great to finally see treatments offered outside the experimental phases. But keep in mind that these new treatments will not be for all patients, and that strict conditions govern their use. Leukodystrophies have as many faces as there are patients and much work remains to be done so that a solution can be proposed for each patient.

• Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Biffi A. et al Science 2013
• Megalencephalicleukoencephalopathy with subcortical cysts: chronic white matter edema due to a defect in brain ion and water homeostasis. Van der Knaap et al Lancet Neurol 2012
• Glycolytic oligodentrocytes maintain myelin and long term axonal integrity. Fünfschilling U. et al Nature 2012
• HIV-1 restriction factor SAMHD1 is a deoxynucleide triphosphate triphosphohydrolase. Goldstone DC et al. Nature 2011
• Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Cartier N. et al. Science 2009

• 1995: Gene transfer assay in patient cells. In vitro manipulation of fibroblasts from ALD patients (Cartier et al.1998: Genetic correction of bone marrow cells. Correction of the gene responsible for ALD (Doerflinger et al.)
• 2005: Successful grafting trial in macaques. Induction of repair of damaged myelin in mice by transplantation of myelin-producing cells into macaques. (Bachelin et al.)
• 2006: Gene therapy trial in mice. Injection of a corrective gene into the brain of MLD mice inducing improvement. (Sevin et al.)
• 2009: A world first: gene therapy to combat ALD. Team of Dr Patrick Aubourg (Cartier et al.)
• 2011: Identification of the POLR3A gene. Evidence of the responsibility of this mutated gene in several leukodystrophies (Bernard et al.)
• 2013: Ex vivo gene therapy to combat MLD. Initiation of a trial in Italy (Milan) in 3 children with MLD, but without disease symptoms (Biffi et al.) In vivo gene therapy to combat MLD. Initiation of a trial in Paris, France, in 5 children with MLD aged 6 months to 5 years (Aubourg et al.)
• 2015: Creation of ELA International.
• 2018: Opening of the Leuconnect platform to facilitate exchanges between clinical trial stakeholders.
• 2019: Opening of the first observational clinical study on Leuconnect: Quality of life in women with ALD led by Dr. Lisa Schäfer under the supervision of Prof. Wolfgang Koehler.
• 2020 : European marketing authorization for atidarsagene autotemcel (Libmeldy), a generic therapy treatment for MLD.
• 2020: Trial of antisense oligonucleotide (ASO) therapy in the PMD mouse model (Elitt et al.).
• 2021 : European marketing authorization for the elivaldogene autotemcel (Skyzona, since withdrawn) generic therapy treatment for ALD.
• 2021: Opening of a clinical trial to test guanabenz in the treatment of CACH syndrome (van der Knaap et al.)
• 2021: Trial of antisense oligonucleotide (ASO) therapy in the rat model of Alexander disease (Hagemann et al.). Followed by the opening of a clinical trial of ASO therapy for the treatment of Alexander disease.
• 2021: Opening of a gene therapy clinical trial for the treatment of Canavan disease (Corti et al.).
• 2022: Opening of the first interventional clinical trial on Leuconnect: SMART-ALD – a lifestyle intervention to improve the quality of life of women with ALD led by Dr. Lisa Schäfer under the supervision of Prof. Wolfgang Koehler.
• 2023: Creation of the ELA International Ethics Committee.

To accelerate research against leukodystrophies, other projects have been initiated and supported by ELA under the supervision of a steering committee.

• The Leuconnect web platform dedicated to leukodystrophy patients and their relatives, with the aim of bringing together people likely to participate in clinical studies in this therapeutic area.
• Gene therapy in adrenoleukodystrophy (ALD) and metachromatic leukodystrophy (MLD).
• Biotin in adrenomyeloneuropathy (AMN) (MD1003, a therapeutic trial with an agent that promotes myelin repair).
• The D3BLeuko biobank (a biobank associated with a clinical database).

• 2006 Paris
• 2009 Luxembourg
• 2015 Paris
• 2017 Luxembourg
• 2019 Luxembourg
• 2021 and 2022 organized in virtual and opened to the international families

ELA has enabled researchers to meet at scientific conferences focused exclusively on leukodystrophies in 2006, 2009, and recently in June 2015. Another congress was organised in 2011 to target new drugs potentially active in leukodystrophies.

The dual objective of these meetings is to exchange knowledge and to encourage interaction between the various players in therapeutic development: scientists, clinicians and industrialists, as well as patients.

ELA works to ensure that research is conducted for the benefit of patients, always with a view to treatment. The annual family researcher conference contributes to this objective by bringing together patients, their families, and researchers.

1. Researchers and research teams submit their project proposals.
2. The Ethics Committee examines the proposals and gives its informed opinion to the Scientific Board.
3. The Scientific Advisory Board rigorously evaluates the projects on the basis of their scientific relevance, feasibility and potential impact.
4. Based on the recommendations of the Scientific Advisory Board, the Management Board decides on the funding of the selected projects.
5. Once funded, the projects are implemented by the research teams, with regular monitoring of their progress by the ELA Research Team.
6. The results of the projects are presented at scientific conferences organised by ELA International, and contribute to the advancement of knowledge and the development of new therapeutic strategies.