Gene therapy a possibility for metachromatic leukodystrophy?

Metachromatic leukodystrophy (MLD) is an inherited disease that causes progressively more severe neurological defects that result in death early in life. Individuals with MLD have a genetic defect that means they lack a protein known as ARSA. There are currently no therapies for MLD, largely because the barrier between the blood supply and brain -- which tightly regulates the substances that can enter the brain -- provides an obstacle that has yet to be overcome. In a study appearing in the November issue of the Journal of Clinical Investigation, Alessandra Biffi and colleagues from the San Raffaele Scientific Institute in Italy, now show that the neurological defects in mice lacking ARSA can be corrected by treatment with hematopoietic stem progenitor cells (HSPCs) genetically modified to express high levels of ARSA. Importantly, ASRA was detected in the neurons of the treated mice and was derived from microglial cells, which differentiate from HSPCs. The successful correction of the protein defect in neurons and of the neurological defects led the authors to suggest that HSPC gene therapy might be efficacious for the treatment of individuals with MLD.


In an accompanying commentary, Harald Neumann, from the University of Bonn in Germany, suggests that studies to determine whether microglial cells could be used as vehicles for gene therapy for other genetic defects affecting the brain should be undertaken.

TITLE: Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice


Alessandra Biffi
San Raffaele Scientific Institute, Milan, Italy.
Phone: +39-02-2643-4681; Fax: +39-02-2643-4668; E-mail: [email protected]

Luigi Naldini
San Raffaele Scientific Institute, Milan, Italy.
Phone: +39-02-2643-4681; Fax: +39-02-2643-4668; E-mail: [email protected].

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ACCOMPANYING COMMENTARY TITLE: Microglia: a cellular vehicle for CNS gene therapy


Harald Neumann
University of Bonn, Bonn, Germany.
Phone: +49-228-6885-541; Fax: +49-228-6885-501; E-mail: [email protected].

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Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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