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Progression of bone symptoms has been greatly alleviated except for pre-existing 
permanent deformities (5-7). It is particularly encouraging that the CNS symptoms of 
a Type 3 patient from Sweden have dramatically improved after marrow transplantation 
and the patient now has normal intellectual function (Professor Olle Ringden, personal 
communication, see also references 6 and 7). 
Marrow transplantation is performed most effectively if a normal HLA-identical sibling 
is used as a marrow donor although significant transplant-related morbidity and mortality 
still occur in a minority of these patients. A majority of Gaucher patients will not have 
an HLA-identical sibling to serve as donor. Non-HLA-matched donors and HLA- 
matched unrelated donors could be used, but the morbidity and mortality risk is much 
greater than that seen with patients having an HLA-matched sibling donor. Because of 
the cost, both in terms of health risks as well as monetary terms, marrow transplantation 
has not been widely utilized in patients with Gaucher disease. 
Enzyme Replacement Therapy for Gaucher Disease 
Since a curative bone marrow transplant is associated with significant risks, alternative 
therapies have been tested. Dr. Brady and his co-workers have developed a placenta- 
derived glucocerebrosidase enzyme which has been modified so that it "targets" to 
macrophages (10-12). This modified enzyme is given to patients to replace the defective 
or absent glucocerebrosidase in their macrophages. The repetitive administration of the 
modified enzyme has been associated with clinical reversal of many of the disease’s 
effects. Enzyme replacement therapy is effective and safe, but enzyme replacement 
therapy is very expensive with the enzyme costing $3.5/I.U. and the usual starting dose 
for a Type 1 patient being 60 IU/kg given intravenously every two weeks. For a 70-kg 
adult the expense for enzyme alone would be almost $400,000 per year. The dose may 
be decreased in future trials, perhaps starting off at one-fourth the dose; this would 
reduce expenses by the same amount but the therapy would still be very expensive. It 
is hoped that once the majority of glucocerebroside in the patient is cleared, a lower 
maintenance dose could be given. Whether an effective maintenance dose would reduce 
yearly expenses much below $100,000 per year is not known. The enzyme replacement 
is an effective therapy for Type 1 Gaucher disease patients but effects on the CNS 
symptoms in the rarer Type 3 patients are not yet known. 
Gene Therapy for Gaucher Disease 
An alternative form of curative therapy could be gene therapy. Retroviral mediated gene 
transfer (RMGT) has been used to transfer glucocerebrosidase cDNA into Gaucher- 
patient derived cells. The enzyme deficiency in hematopoietic cells from Gaucher 
patients has been corrected following retroviral mediated gene transfer into CFU-GM 
progenitor cells (13). High efficiency transfer into more primitive hematopoietic 
progenitor cells has also been seen (14). Both studies reported enzyme levels in the 
patient cells that are equivalent to those found in normal individuals. By transferring the 
glucocerebrosidase cDNA into patient marrow progenitor cells ex vivo and then returning 
the primitive cells to the patient it may be possible to let the patient serve as their own 
bone marrow stem cell donor. Autologous marrow transplantation is associated with 
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