Andy i judt found this. Appearantly the first gene therapy trial has already been successful...
this is the link:
http://docs.google.com/viewer?a=v&q=cache:gIQcRs6RAlkJ:www.esh.org/ChaptersIronHB/IRON2009_CAP.15(390-401).pdf+update+of+the+first+human+trial+(Yves+Beuzard+replacing+Philippe+Lebouch,+Fontenay-aux+Roses).&hl=en&gl=uk&pid=bl&srcid=ADGEESj219CGufFePBFeW-VuQZyyomnN9a3hzjZznoks0j_ek--EFXTPNAHV6Bl35FpL00Mrw-xIhhhIHo1flEDcvE9wFnJY0O1gd9J7H2PLAz4qG4pE_7mH3JGRMDRyO_RQluuvbZIP&sig=AHIEtbSapvzEfa6sRl7F67c4sGjFobm_aQThe first patient with severe thalassaemia who underwent a complete procedure without
injection of back-up cells was given the globin gene therapy at age 18 years. He
suffered from severe anaemia due to the bE/b0 thalassaemia genotype requiring regular
transfusions (about 160 mL of packed erythrocytes/kg/year) from the age of 3
years. Attempts to replace transfusions by hydroxycarbamide (hydroxyurea: Hydrea®)
were unsuccessful and there was no suitable familial donor for HSC transplantation.
He received 4x106 CD34+ cells/kg. Twenty months after gene therapy, the patient
did not suffer any side effects associated with the procedure as a whole. The
proportion of LG-modified blood nucleated cells rose progressively (Figure 3A) to
6% after 12 months (assuming not more than one copy of the integrated vector per
cell). The requirement for transfusion declined progressively and transfusions were
no longer necessary after 12 months. The concentration of therapeutic haemoglobin
in blood reached 2.8 g/dL (1/3 of total haemoglobin) 7 months after the last
transfusion (19 months after GT) (Figure 3B and 3C).
Anaemia was stabilised (Hb between 8 and 8.5g/dL) following transfusion but the
persistent high reticulocyte counts (not shown) indicate that the genetically
modified erythroid cells compensated only partially for the deficits of red cells and
haemoglobin. The proportion of therapeutic b-globin chain in reticulocytes was low
and variable (2-8% of total Hb). Most probably, therapeutic b-globin was distributed
among only a small proportion of reticulocytes. The large increase in the proportion
of the therapeutic Hb in blood (33% of total Hb) and the low proportion in
reticulocytes (mean 3%) suggests that the b-globin-containing reticulocytes
generated red cells with an increased survival, probably close to normal life
expectancy of healthy red cells. The abundance of foetal Hb (HbF) in reticulocytes
increased transiently following patient conditioning and decreased during the
recovery from aplasia. Before gene therapy, when the patient was hypertransfused,
the proportion of HbF in reticulocytes was 26%, rising to 57% in reticulocytes 2
months after the GT procedure and subsequently progressively decreasing around
20%, 6 months after the last transfusion and 18 months post gene therapy.
Vector-bearing cells were not uniformly distributed in all cell types: they made up
8-12% of granulocytes, 9-13% of early erythroid progenitors, 2-4% of circulating
erythroblasts, 6% of B lymphocytes and less than 1% of T lymphocytes. There
appeared to be a weak selection for modified common myeloid cells over lymphoid
progenitors; alternatively, B lymphocytes may just have a lower turnover than myeloid
cells. The low proportion of genetically modified T lymphocytes is very likely due
to the fact that cyclophosphamide was not used for conditioning. Busulphan alone
is not believed to kill T cells. The reason for the low proportion of circulating
erythroblasts carrying the vector as compared to early erythroid progenitors is not
known. Interestingly, the proportion of modified early erythroid progenitors (as
detected by PCR analysis of colonies) was similar to the proportion of colonies
producing the therapeutic haemoglobin (determined by HPLC) suggesting negligible
silencing (position effect variegation) of the therapeutic transgene, protected by
the chromatin insulator flanking the integrated vector.
At the most recent follow-up examination, blood and bone marrow cells from this
patient had normal morphology other than the thalassaemic features remaining in
a large proportion of cells. Importantly, the patient reported good wellbeing. His
life is transformed and he is free from doctors, transfusions and frequent blood tests.
He is able to perform his full time job without fatigue. Life-long follow-up with
periodic evaluation will be required to determine the stability of the corrected
phenotype, the long-term survival of repopulating HSCs and oncogenic safety.
In summary, this historical patient, who underwent ex vivo globin gene transfer for
a frequent and severe genetic disease provides the proof of principle of this
therapeutic approach. In particular, the case demonstrates that large amounts of
a therapeutic protein (b-globin) can be produced in vivo (84 g/L of red cells which
is close to the amount of globin produced by the expression of one normal
endogenous b gene) and that production can be limited to a single appropriate
lineage of cells and differentiation stage by use of a tissue specific transcription
system (erythroid promoter and globin LCR) involving a single copy of a “full” gene
(containing introns). The case also validates somatic gene transfer using a lentiviral
SIN vector with chromatin insulators for transducing long-term repopulating
haematopoietic stem cells. It demonstrates that somatic gene transfer, ex vivo, can
provide transfusion independence for a patient with severe HbE/b0 thalassaemia
disease, the most frequent b-thalassaemia genotype in the world.
For the most severe thalassaemic patients to be included in this trial, we propose
to double the proportion of transduced erythroid progenitors to 20%, so as to provide
more than 5g of therapeutic Hb/dL of blood, as this should be sufficient to improve
the b0/b0 thalassaemia major severe phenotype similar to the improvement
associated with a stable 20% chimerism provided by an allogeneic haematopoietic
transplantation (10).
i hope this is alll true!