Metachromatic Leukodystrophy

Current Treatment of MLD

The treatment of MLD can be divided into two categories:

Supportive treatment for a patients and families of patients.

This includes taking all possible measures to improve the quality of life for the affected individual and to provide genetic counseling to individuals at risk to have a child with MLD to enable them to make informed decisions.

Attempts to treat the primary disease process.

There are no established treatments for the primary disease process in MLD.

For a number of years, bone marrow transplants (BMT) were used in an attempt to treat MLD. In this procedure, the individual with MLD undergoes a treatment that removes the blood cell forming cells in their bone marrow and these cells are replaced by bone marrow cells from a donor.

The objectives are for the donor cells to become engrafted within the MLD patient and produce blood cells that have normal levels of arylsulfatase A. The hopes are that some of this ASA and perhaps some of the engrafted donor cells will enter the nervous system and break down existing accumulated sulfatide and prevent further storage.

The success of bone marrow transplants has been somewhat controversial for a number of years. It is safe to say that BMT are not a "cure" but optimistically may help some patients by slowing the rate of disease progression. In other patients BMT has not been a successful treatment. There is little evidence to suggest that once neurological damage is done that a BMT can correct that damage or reverse clinical symptoms. BMT is an invasive procedure with a risk of morbidity and mortality.

More recently hematopoetic stem cell (HSC) transplants and umbilical cord blood transplants have been used in attempts to treat MLD. These procedures are generally similar to BMT but use different donor cell populations. Children who receive umbilical cord blood transplants seem to tolerate the procedure with a lower incidence of rejection and other complications than typically seen with BMT and HSC transplants. There is insufficient experience and data to know if the outcomes are better than BMT.

The rate of progression of MLD can vary from patient to patient and can last over many years. This variability makes it difficult to know whether a treatment has been successful in slowing or halting the disease process. It is recognized that detailed studies of the natural history of untreated MLD and effective assessment tools are needed monitor the effectiveness of all experimental treatments.

Zymenex (http://www.zymenex.com) has recently recruited patients for a Phase I/II clinical trial of enzyme replacement therapy for MLD. Information on this trial should be available during 2008. Shire (http://www.shire.com) has also identifed MLD as a disorder to develop a treatment using Shire's enzyme replacement therapy platform.

There is a good website to monitor approved clinical trials: ClinicalTrials.gov