[Research ] - Bethanys Hope

	Metachromatic Leukodystrophy Metachromatic Leukodystrophy (MLD) is a devastating progressive neurodegenerative disease that has no cure. It targets the nervous system and destroys the white matter in the brain with the affected child often dying by about five years of age. Humans have about 25000 genes and we know that MLD is caused by an error in one gene called ARSA . The ARSA gene has a DNA sequence that codes for an enzyme named arylsulfatase A. In our brain and peripheral nerves the role of arylsulfatase A is to break down a molecule called sulfatide into smaller components. When there is a mistake in the ARSA gene, sulfatide is not broken down and its accumulation in the brain causes MLD. Our research objectives are: • To develop cellular and mouse models of MLD. • To understand why brain cells die in MLD. • To develop gene transfer vectors to introduce a stable correct ASA gene ....into the MLD mouse brain. • To develop procedures to enable gene transfer vector to cross the blood ....brain barrier in the MLD mouse. • To identify potential pharmacological targets. To determine the safety and any ill effects of these procedures in mice. .
	The first three objectives have been accomplished and Bethanys Hope Leukodystrophy Research Laboratory is focusing on developing procedures for getting the gene transfer vectors into the brain. This is a challenging problem. Recently we have identified cells in the brain called microglia that scavenge sulfatide. ....
		In the top panel are microglial cells that are green because they have taken up sulfatide. Normally sulfatide has no color and cannot be seen under the microscope but we chemically synthesized a type of sulphatide that is green when viewed with the flourescent microscope. In the lower panel are microglia cells that are both red and green. The green is from sulfatide and the red is from an antibody used to identify and distinguish microglial cells from other types of cells.

	Microglia cells in the brain are closely related to macrophage cells that circulate in blood. We are researching the possibility of using the accessible macrophages to enter the brain and become microglial cells. Can we use macrophages as Trojan horses to deliver a corrected ARSA gene?

		The green dot is a macrophage cell that has migrated from blood into the brain of the MLD mouse.