20 years on myelin research : the interview of Pr Charles ffrench-Constant



Written on Thursday 11 April 2013

Honoring the 20th ELA anniversary, Pr. Charles ffrench-Constant, recongnized expert on myelin research, chairman of the Scientific Committee of the ELA Foundation and director of the MRC Centre for Regenerative Medicine at the University of Edinburgh (Scotland), tells us about the research advances on myelin biology and repair.

 

 

 

How the field on myelin biology has evolved over the last 20 years?

Evolution has been considerable.  Building on cell work in 80s, we now have a good understanding of molecular mechanisms that lead to generation of oligos from precursor cells.  We also now understand the relationship between oligos and stem cells in adult brain. However we still have a poor understanding of the mechanisms of perhaps the most remarkable feature of myelin biology – how does a oligo form a large number of sheaths composed of as many as 50 membrane wraps and each exactly correct in size for the axon being myelinated.

 

Do we understand better the mechanisms leading to myelin damage?

In multiple sclerosis (MS), careful neuropathological studies have greatly improved the understanding of how the immune system can damage myelin.  In leukodystrophy, progress has been slower and we still have important questions to address.

 

In what circumstances endogenous remyelination occurs in humans?

The neuropathology has revealed that remyelination can be extensive in MS, especially early in the course of the disease.  We have known for some time that experimental lesions in animal models can repair very well – the finding that such repair was so extensive in humans was a surprise, but a very important discovery.  In leukodystrophy, remyelination is much less studied but given that the disease usually results from an abnormality of the oligodendrocyte itself the amount of endogenous repair is likely to be small.

 

How can we promote endogenous remyelination in humans?

This is one of the major goals of current MS research, and we now have a handful of possible targets for drug development.

 

Is cell therapy a good option to repair myelin?

We need to be very clear what we mean by cell therapy and which diseases we are trying to treat.
If we are trying to put in new oligodendrocytes to replace damaged cells, then this will be a limited option for MS as the disease is so widespread and it would be difficult to get cells to spread far enough in the damaged adult brain. For leukodystrophy cell replacement therapy is much more promising as :

  • the disease is usually due to an intrinsic cell abnormality rather than an external immune attack
  • the childhood brain is smaller and “primed” for myelination as this normally occurs for at least 20 years after birth.

However we will need to use oligodendrocytes from another individual as the patients own cells will still have the genetic defect.

 

How do you see the transition from the lab bench to the bedside?

With increasing optimism – researchers are now focusing on this transition, as is ELA in its funding priorities, and the science is now poised for clinical application.  We need a generation of young clinicians trained in leukodystrophies to deliver this promise, and here again ELA is leading efforts to find and train the best young medics.

 

Most of the research done on the myelin field focuses on MS. Can we expect more research focusing on leukodystrophies? If not, how can we improve it?

I am confident that we will see much more leukodystrophy research.  It’s clear that treatments are now a realistic possibility and that advances in gene and cell therapy offer wonderful new possibilities. At the same time, our understanding of the basic science has progressed to the stage where clinical application is possible and we have developed sufficiently good technologies so the results of treatments can be accurately measured. By making sure that funding continues for this vital research, we can ensure that the possibilities are realized

 

How do you see the field advancing in the future?

To the clinic!!

 

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