06/03/93 09 : 42 
H UMAN GENETICS - B3T - (JNIU PITT 
009 
John A. Barranger, M.D.j Ph.D. 
June) i 1993 
are very Important In Gaucher disease. All of your cells lack sufficient lamounts 
of glucocerebrosidase, but for some unknown reason, only macrophages stoneiup the 
body lipid (a kind of a fat) that GC has the job of breaking down. So you see, 
macrophages play a central role in Gaucher disease and are responslblelfor the 
big liver or spleen and bone problems that you have. It is important that you 
know that these macrophages come from your bone marrow. The bone marrow Is like 
a factory sending out cells to do various jobs in the body. One of tho^e jobs 
is to clean up old cells and debris left behind by building up body [parts or 
fighting the wars with bacteria and other foreign organisms. Again, these|"clean 
up cells" or macrophages are sent out by your bone marrow all the time*' Each 
macrophage does its job for about 3 months and then is itself replaced (by a new 
one which comes from the bone marrow. 
In Gaucher disease, the macrophages coming from the bone marrow ;lack a 
sufficient amount of this enzyme - GC - to do the job of breaking down thi$ fatty 
material. We have shown that a new bone marrow from a donor can tf£at the 
disease. Unfortunately, many patients do not have a donor and the 
transplantation of donor marrow carries a significant risk. Estimates ajre that 
10-25% of those patients receiving a donor transplant will die. Only ih a few 
patients is this risk justifiable. Furthermore, enzyme replacement, whild useful 
as a treatment, Is not a cure and is expensive. 
Our plan is to correct the deficiency of GC by adding a good gene ito your 
bone marrow which contains the cells that reproduce and make macrophages for 
life. As I indicated, we have already corrected skin cells from jGaucher 
patients. We have also shown that we can get mouse bone marrow cells tijmake GC 
for a long time both In laboratory cultures and In whole mice. We have also 
shown that the good gene works in human macrophages to make GC the same way as 
It does in Gaucher patient skin cells and mouse bone marrow. 
The first step in this study is to put a good gene for GC Into c 
can make an entirely new bone marrow. We have learned that we can 
cells from your blood. They can be collected by connecting you to 
which separates white blood cells (leukopheresls) . The bone marrow-maKi 
are purified from the white blood cells in the laboratory. We will usje 
in the laboratory to put the good gene into these cells. These methods 
the use of a virus as a vehicle for carrying the gene Into the cel 
virus has been' altered so that 
disease. However, there is a possibility that tn Is virus could cause 
some other problem not yet identified. The risk of this occurring is 
to estimate, but theoretically is a small one. So far, in animal 
studies, no problems have occurred, but you should know that not 
studies have been done and, thus, the experience is short. 
ills that 
dt these 
1 machine 
ig cells 
methods 
involve 
Is. The 
nbt cause 
cancer or 
difficult 
ahd human 
vfery many 
Following these procedures to put the good gene into your Don 
making cells, we will put these genetically corrected cells into 
stream. They will find their way Into your bone marrow where they 
blood cells including the important macrophage. We do not know how ma 
genetically corrected cells will be required to establish a populatl 
that will result in a good clinical change in your condition. We reasdn 
marrow- 
yo,ur blood 
vjill make 
ny of your 
of cells 
! that the 
01 
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Recombinant DNA Research, | Volume 17 
