On April 4th 2014 the ELA Foundation’s Scientific Council organized the first ELA scientific day in Paris.
This event was organized the day before the 2014 ELA Families / Researchers meeting and was offered to scientists working in the field of leukodystrophies. It was an occasion to discuss the progress made by the research projects ELA is funding and more generally the research progress in this field.
The detailed day’s programme
8:45 am Welcome
Professor Charles ffrench-Constant, president of the ELA Foundation’s Scientific Committee
9 a.m. Scientific session 1 – Diagnosis of leukodystrophies
Chair: Professor Jean-Louis MANDEL (France)
- New genes identified for undetermined leukodystrophies – Professor Enrico Bertini (Italy)
- Improving the diagnosis of leukodystrophies – Professor Jean-Louis Mandel (France)
10 a.m. Scientific session 2 – Understanding the mechanisms of leukodystrophies
Chair: Professor Raul ESTEVEZ (Spain)
- Understanding Aicardi-Goutieres syndrome – Dr Yanick Crow (UK)
- Mechanisms responsible for polymerase III-related leukodystrophies – Dr Genevieve Bernard (Canada)
11 a.m. Scientific session 3 – New experimental models for leukodystrophies
Chair: Professor Volkmar GIESELMANN (Germany)
- Development of experimental models for megalencephalic leukoencephalopathy with subcortical cysts (MLC) – Professor Raul Estevez (Spain)
- An in vitro model of vanishing white matter disease – Dr Marie Harrisingh & Professor Charles ffrench-Constant (UK)
13 p.m. Scientific session 4 – Therapies for leukodystrophies
Chairs: Professors Patrick AUBOURG (France) & Alfried KOHLSCHÜTTER (Germany)
- Gene therapy by intracerebral transfer of the ARSA gene for MLD – Dr Caroline Sevin (France)
- Gene therapy for Canavan disease – Dr Guangping Gao (USA)
- The effect of physical exercise on the function and pathology of women with adrenomyeloneuropathy – Dr Kathleen Zackowski (USA)
- Evaluating the effects of a cocktail of antioxidants in patients with adrenomyeloneuropathy – Dr Aurora Pujol (Spain)
- Presentation of the MD1003 clinical trial in adrenomyeloneuropathy – Dr Frederic Sedel (France)
- Phase I/II clinical trial of hematopoietic stem cell gene therapy for the treatment of metachromatic leukodystrophy – Dr Alessandra Biffi (Italy)
16 p.m. Conclusion of the scientific day
Professor Charles ffrench-Constant, president of the ELA Foundation’s Scientific Committee
Documents to download
Renowned scientific and medical experts working in the field of hypomyelinating leukodystrophies and neuroradiology (see list below) and members of the ELA Foundation’s Scientific Committee met on October 13th in Leipzig, Germany for the ELA international symposium titled “MRI markers of efficacy for clinical tests on hypomyelinating leukodystrophies”.
Currently, MRI (or Magnetic Resonance Imaging) is the only tool which can be used to diagnose hypomyelination which is a lack of myelin. It is still early days for therapeutic tests for hypomyelinating leukodsytrophies and we urgently need to identify markers to evaluate the potential benefits of experimental treatments.
The objective of the working group, directed by Drs David Rowitch and Wolfgang Köhler, members of the ELA Scientific Committee, and the neuroradiology expert Professor James Barkovich, was to identify clinical and radiological MRI assessment criteria which could reasonably be used for future clinical trials.
Before getting to the main subject, the group discussed basic myelin biology and the clinical challenges linked to hypomyelinating leukodsytrophies. The following MRI techniques were then described and discussed at length:
- magnetic resonance spectroscopy
- Magnetization transfer in MR
- nuclear magnetic resonance diffusion imaging
- neuromuscular monitoring with resonance imaging and the myelin water fraction
- quantitative MRI
Next there was a stimulating multidisciplinary discussion around questions such as:
- Which clinical parameters are specific to hypomyelinating leukodsytrophies?
- Can myelin be quantified by existing technologies?
- Which are the best techniques and how can these be integrated into clinical tests?
- Which are the most appropriate radiological parameters?
- How can myelin be quantified?
The discussions between the experts led to the identification of clinical and radiological MRI criteria which will be used both to assess experimental therapies and to improve diagnosis and medical monitoring of patients with hypomyelinating leukodsytrophies. The group also identified future lines of research aimed at developing MRI technologies and measuring myelin.
The group of multidisciplinary experts’ recommendations and consensus advice will soon be made public after publication in a scientific journal.
The experts invited
|Name||Affiliation||Area of expertise|
|James BARKOVICH||University of California, San Francisco, CA, USA||Pediatric neuro-imaging|
|Geneviève BERNARD||McGill University, Montreal, Canada||Clinical research into leukodystrophies|
|Enrico BERTINI||Bambino Gesù Hospital, Rome, Italy||Clinical research into leukodystrophies|
|Sean DEONI||Brown University, Providence, Rhode Island, USA||MRI|
|Steffi DREHA-KULACZEWSKI||University of Göttingen, Germany||Clinical and MRI research into leukodystrophies|
|Charles ffrench-CONSTANT||MRC Centre for Regenerative Medicine, Edinburgh, Scotland||Research into myelin|
|Günther HELMS||University of Göttingen, Germany||Clinical and MRI research into leukodystrophies|
|Wolfgang KÖHLER||University Medical Center Hamburg-Eppendorf, Hamburg, Germany||Clinical research into multiple sclerosis and myelin illnesses in adults|
|Alfried KOHLSCHÜTTER||Université du Centre Médical Eppendorf, Hambourg, Allemagne||Clinical research into leukodystrophies|
|Petra POUWELS||VU University Medical Centre, Amsterdam, Netherlands||Clinical research into leukodystrophies|
|William RICHARDSON||University College London, United Kingdom||Research into myelin|
|David ROWITCH||University of California, San Francisco, CA, USA||Clinical research into leukodystrophies|
|Adeline VANDERVER||Children’s National Medical Center, Washington DC, USA||Clinical research into leukodystrophies|
|Ronald WANDERS||Academic Medical Centre, Netherlands||Research into peroxysosomal illnesses|
|Nicole WOLF||VU University Medical Centre, Amsterdam, Netherlands||Clinical research into leukodystrophies|
Around twenty experts specializing in leukodystrophies and other neurodegeneratives diseases like multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis met on January 13th and 14th 2012 in Paris at the first symposium on adrenomyeloneuropathy (AMN) organized by the ELA association in collaboration with the Stop ALD foundation.
As well as these experts, representatives of patients also attended the symposium as observers. Discussion was thus enriched by short exchanges between patients and experts.
The aim of the symposium was to identify new therapeutic approaches for adrenomyeloneuropathy, the adult form of adrenoleukodystrophy, for which there are currently few therapeutic options available and to particularly focus on the therapeutic tests which ELA is funding.
Guy Alba, the president and founder of the ELA association, and Amber Salzman, president of the Stop ALD foundation, first thanked those present for taking part and then reiterated the aim of the symposium.
Professor Patrick Aubourg next described the disease’s clinical, genetic, physiopathological and radiological aspects and Aurora Pujol presented the characteristics of the animal model for adrenomyeloneuropathy.
Basic knowledge about the disease was first discussed and then the symposium continued in the form of work groups focussing on adrenomyeloneuropathy without cerebral damage. Guy Alba and Amber Salzman acted as moderators for these groups.
The three following themes were discussed;
- anti-oxydative strategies for AMN,
- agents which target the function, protection and/or axonal repair for AMN,
- tools and clinical tests aimed at providing effective clinical evaluation of AMN.
To move away from more classical over-formal scientific presentations, the symposium format was set up so as to facilitate informal discussions between experts and the sharing of opinions.
“Anti-oxydative strategies for AMN” work group
This work group concentrated on the identification of the most promising molecules to fight oxydative stress – both anti-oxydants or agents which target the mitochondrial function – tested for other neurodegenerative diseases than AMN.
When the toxicology of these molecules for humans was known this was discussed. The group also studied the biological targets of these agents, their specific features, time course of drug action in the organism, their ability to cross the blood-brain barrier and the risks of toxicity involved in using heavy dose. There was also discussion of the right dose to give human patients as based on effective doses given to animals.
Finally the possibility of additive effects resulting from the combination of different molecules was discussed.
“Agents which target the function, protection and/or axonal repair for AMN” work group
This session was based on the antioxydants work group and dealt with axonal, and therefore nerve, problems. It dealt with new drugs which are either available or being developed as treatments for other neurodegenerative diseases and which help increase the axonal function and improve patients’ mobility.
“Tools and clinical tests aimed at providing effective clinical evaluation of AMN” work group
The choice of clinical and biological tests is crucial for the successful evaluation of a treatment’s effects on diseases which develop slowly like adrenomyeloneuropathy without cerebral damage.
The group agreed that clinical tests for patients need to be simple. The endurance test involving a 6-minute walk was cited as a reference. Biological markers could also be measured as far as is reasonable.
Different evaluation scales will need to be measured during the test including scales of pain, tiredness, motricity and quality of life.
Female carriers of the gene responsible for the illness will be able to take part in therapeutic tests as well as male patients with AMN who have previously received a bone marrow transplant. Patients will be able to continue taking their medicines to treat their illness unless these interfere with the drug being tested.
To sum up, the 1st symposium on adrenomyeloneuropathy highlighted different therapeutic ideas which were then presented and discussed at the round table at the 2012 ELA conference for families and researchers at the end of March.
Before launching therapeutic testing, it is essential to study the different compounds, their side-effects, availability on the market and regulatory processes as well as the technical ability and expertise of the medical teams running such tests.
The ELA association has set the following conditions for funding therapeutic testing:
- tests must use simple clinical tests,
- testing should not last longer than two years and an a minima intermediate evaluation should take place after 1 year,
- tests will not use placebos,
- those running tests will need to obtain all the necessary prior authorizations from the right health regulations bodies
The experts invited
|Patrick Aubourg||Bicêtre Hospital, Paris, France|
|Flint Beal||Weill Cornell University, New York, NY, USA|
|Nathalie Cartier||Inserm U-745, Paris, France|
|Florian Eichler||Mass Gen Hospital, Boston, MS, USA|
|Marc Engelen||AMC, University of Amsterdam, Netherlands|
|Bjorn van Geel||Alkmaar Medical Centre, Alkmaar, Netherlands|
|Richard I. Kelley||Kennedy Krieger Institute, Baltimore, MD, USA|
|Stephan Kemp||AMC, , University of Amsterdam, , Netherlands|
|Wolfgang Köhler||Hubertusburg Hospital, Wermsdorf, Germany|
|Jörn Kühl||Charité Hospital, Berlin, Germany|
|Catherine Lubetzki||La Pitié Hospital, Paris, France|
|Paul Orchard||University of Minnesota, Minneapolis, MN, USA|
|Aurora Pujol||Weill Cornell University, New York, NY, USA|
|Michael Racke||Ohio State University, Colombus, OH, USA|
|Gerald Raymond||Kennedy Krieger Institute, Baltimore, MD, USA|
|Seward Rutkove||Beth Israel Deaconess Medical Center, Boston, MS, USA|
|Frederic Sedel||La Pitié Hospital , Paris, France|
|Kathleen Zackowski||Institut Kennedy Krieger, Baltimore, MD, USA|
Representatives of patients present
|Guy Alba||ELA Association, France|
|Amber Salzman||Stop ALD Foundation, USA|
|Pascal Prin||ELA Association, France|
|Rachel Salzman||Stop ALD Foundation, USA|
|Carlos Chiclana||ELA Association Spain, Spain|
|Günther Förstner||Association Bundesverein Leukodystrophie e.V., Germany|
|Mark Bostock||ALD Life Association, United Kingdom|
|Mark Liley||Olivers Army Association, United Kingdom|
The ELA Research Foundation organized its 2nd Scientific Congress entitled “Therapeutic challenge in white matter diseases” on June 26 & 27, 2009 at the European Institutions in Luxembourg.
This congress, dedicated to international specialists in leukodystrophies and myelin repair, allowed them to share and learn from recent scientific advances in these particular fields. Five topics were adressed during the scientific communications:
– Stem cell and gene repair
– Biology of myelination/remyelination
– Cognitive functions and demyelination disorders
– Neuroimaging in CNS white matter disease
Numerous poster presentations were also displayed.
The 1st International Congress of the ELA Research Foundation & The Myelin Project entitled “The vital function of myelin development and maintenance” took place in Paris from October 5 to 7, 2006. The Scientific Committee in charge of the meeting organization was composed of Prs. Aubourg, Dubois-Dalcq, Boespflug-Tanguy, Lacaze and Baron-Van Evercooren.
Over 200 participants (M.D., Ph.D, Postdocs and Ph.D. students) from around the world specialized in leukodystrophies and myelin repair attended the meeting and presented their latest results.
The congress was divided in four different scientific sessions:
– Myelin development and repair
– Pathological mechanism of myelin disorders
– White matter disease of the premature
– Genetics & Therapeutics of Leukodystrophies
Among the numerous scientific discoveries presented during the meeting, we can point out that various molecules implicated in the production of myelin have been identified and represent potential candidates for future therapeutic applications. Also, new leukodystrophies have been described:
– Leukodystrophy with progressive ataxia*, deafness and cardiomyopathy**
– Leucoencephalopathy with delayed dentition and hypomyelination
– Leucoencephalopathy HCC characterized by hypomyelination and congenital cataract. Identified gene: hyccin
– Pelizaeus-Merzbacher-like disease with ataxia* and spasticity***. Identified gene: GJA12
New imaging technologies that can be used as diagnostic and to monitor disease outcome have been developed. It is now possible to perform MRI in prematures. Moreover, the measure of water diffusion by MRI allows evaluating the brain microstructure in children. Today, blood and urine sulfatides can be measured by mass spectrometry and long chain fatty acids can be quantified using liquid chromatography combined with mass spectrometry in newborns.
*Ataxia: Unsteady movements that result from the brain’s failure to regulate the body’s posture and the strength and direction of movements.
**Cardiomyopathy: Disease weakening the heart muscle which usually causes inadequate heart pumping.
***Spasticity: Stiff or rigid muscles and exaggerated deep tendon reflexes that interferes with muscular activity, gait, movement, or speech.