Looking back over noteworthy facts pertaining to research into leukodystrophies with Pr. Patrick Aubourg

Written on Wednesday 12 December 2012

This year, the ELA association is 20 years old. Pr. Patrick Aubourg, neuropediatrician at the Bicêtre Hospital and a renowned specialist of leukodystrophies, who has followed the progess of the ELA association since its conception, retraces for us the major advances of research into leukodystrophies over the last 20 years.

To what extent has knowledge concerning leukodystrophies progressed over 20 years?

According to my point of view, knowledge of leukodystrophies has progressed on three major points:

  1. Over the years, the number of leukodystrophies has increased, to a terrible extent even. Twenty years ago, only 5 or 6 leukodystrophies had been genetically identified, whereas today I think we recognize 27 or 28 and we discover 3 new ones each year. In consequence, in the absence of a therapy we can propose genetic counselling and prenatal screening for these diseases, which is still a crucial element.
  2. The myelin defect due to an abnormality in the formation or maintenance of the myelin sheath in leukodystrophies is clearer on the biological plan. We now know that not only the oligodendrocyte cell that synthesizes this myelin is involved. This can be the case, but there are other brain cells that we call by complicated names -astrocytes, microglial cells, etc.- which interfere and interact.
  3. We have gone past the stage of mere diagnosis and trying to help the patients as far as possible, to that of therapy. We have benefited from progress in the domain of brain and spinal cord diseases and from new approaches at the therapeutic level, whether they be pharmacological, Gene therapy" class="glossy" title="Procedure involving the insertion of a normal gene into an organism in order to achieve a therapeutic objective. This gene (transgene) can be the normal version of a defective gene causing disease or a gene that produces a protein with any therapeutic action." >gene therapy or cellular therapy. Certain of these have already gone into the clinical phase, i.e. the first trials have been carried out and are more than encouraging for the future. An enormous step has thus been taken in recent years.

 What are the next challenges?

The challenge remains enormous, because for each leukodystrophy a relatively specific therapeutic approach is required. Certain treatment tools use similar methodologies and technologies, for example I am thinking of the principle of gene therapy that aims to use a vector drug to insert the normal gene into the correct cells of patients’ brains. However, for each disease there will be a distinct therapeutic approach. We must also keep our feet on the ground, since these therapeutic approaches will only be efficient at the beginning of the illness. Thus, as soon as we have shown the efficiency of a treatment, we must envisage as soon as possible the screening for certain of these leukodystrophies at birth. This will change everything.

In the fight against leukodystrophies, what role has ELA played in the development of medical research?

ELA has acted as a catalyst on two essential levels:

  • Firstly, by bringing together to work on leukodystrophies initially French, then European and now international Doctors and researchers.
  • Secondly, it is the financial aspect of preclinical research –i.e. that carried out before going into treatment– that keeps the studies alive, but also clinical trials.

Particularly as far as I am concerned, many things could not have been achieved without the highly active financial support of the ELA association and its foundation.

How does the future look?

The future seems very promising and that is important for all the families concerned. Even if for certain diseases one will need to be patient, even if it remains expensive, research today advances more rapidly than it could have 5 years ago. It is thus indispensable that everybody rally around ELA. I will only give one example: to treat 4-5 patients by gene therapy costs around 4 million euros! Obviously there are complementary subsidies from the European public powers, but ELA remains a crucial partner in this therapeutic war. If we have to forge ahead every day, we need to join forces for that!

For more details, see: Assessment of 20 years of research into leukodystrophies (in French)