Research into MLD Metachromatic Leukodystrophy


Enzyme Replacement Therapy (E.R.T.)

If you look at the NHS Specialised Services web pages for Lysosomal Storage Disorders, you might be forgiven for thinking that there is E.R.T. treatment available for this group of rare genetic conditions. However, it goes on to list only six of the 50+ named disorders within the group, and Metachromatic Leukodystrophy is not yet amongst them. Furthermore, we need to be aware that it is only therapeutic treatment which is available—in other words it would only be used to reduce the effects of the condition, and not to cure it. That’s the bad news.

The good news is scientists within 14 European countries who are working as a consortium organised by a European Charity called ‘Brains 4 Brain’. They are trying to improve the chances of finding a way to correct the deficiency of the enzyme or protein which is considered to be the cause of the degeneration. [The European Task Force on Brain and Neurodegenerative Lysosomal Storage Disorders].

In the case of MLD it is generally the enzyme Arylsulfatase-A, or occasionally a protein called prosaposin, which is deficient. However, that is not the full story, and some of the team are trying to discover whether there are other processes which might be more important. Meanwhile some of the groups are researching methods of ‘topping up’ the enzyme/protein shortfall to prevent further breakdown of the Myelin Sheath (the protective covering of nerves) which has been caused by the inability of the cells to discharge the waste matter (sulfatides) from the brain.

The problem is that, although they believe they know what is required, and where it should be introduced, they have not yet been able to find a fully effective way of reaching the white matter in the brain and spinal cord which is responsible for myelin production. Various clinical trials are being attempted, but they are not yet advanced or positive enough to offer any solutions. The ‘blood brain barrier’ which acts as an anti-toxin defence of the CNS (Central Nervous System), has proved to be the main barrier to the introduction of the required enzyme. The favourite candidates for enzyme replacement therapy methods are Intravenous (i.e. through the blood), and Intrathecal (i.e. into the space under the protective membrane surrounding the brain and spinal cord). In both cases the effects are limited, as they seem to improve the efficiency of the white cells in the immediate area only, and not deeper into the white matter. There are teams working specifically on ‘transporting’ through the blood brain barrier without damage to the protective cells, and this is a mammoth task. They have made some progress in recent times, and the annual conference of the task force is when the research programmes come together so that they can share their ideas and results.


Other research

There are other research groups and clinicians working on the possibility of alternative gene therapy or the use of drugs as a therapeutic treatment.

One group, in France, are trialling Intraventricular (i.e. into the ventricles {spaces filled with cerebrospinal fluid}) gene therapy using the patient’s own stem cells. Another trial is ongoing in Milan using the patient’s own stem cells (after genetic modification) into the blood stream. One North American company is researching the use of ‘small molecule’ drugs.

Shire Human Genetic Therapies (a division of Shire plc) are conducting research into an enzyme replacement therapy for MLD. Shire has produced a recombinant human MLD molecule, which is currently being tested for safety in a small Phase 1 clinical trial. They are also gathering information on the natural history of MLD.

About us

MLD Support Association UK was set up to bring hope to families in the fight to eradicate Metachromatic Leukodystrophy (MLD). Our aim is to provide support by way of shared information from people in similar circumstances who have already experienced the effects of the condition and/or any treatments available.

MLD Support Association UK

MLD Support Association UK is a
Registered Charity Number 1150542

Professor Timothy M Cox, MD, FRCP, FMedSci
Suzi Digby (Lady Eatwell) OBE
Iain Stewart MP


MLD Support Association UK
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Tel: 07977 440809