B50 as
the Next Lead Candidate for hematopoiesis
Plants Screened
A total of 21 herbs used
in TCM tonics were selected, extracted and screened for hematopoetic potential using in vitro assays for cytokine production. Extracts
from as many as 15 of these plants were found to be highly active at inducing G-CSF
production in human peripheral blood mononuclear cells.
Extracts from 13 of these plants were tested in animal models for
hematopoietic activity. Initial in vivo
studies showed that 6 of them demonstrated promising activity in
promoting early recovery of peripheral blood from radiation- or
chemotherapy-induced myelosuppression in mice, and in stimulating recovery of
hematopoietic progenitors from these therapies. This is a remarkable hit rate compared to typical
pharmaceutical screening. One plant,
B2, was selected and studied in greater detail by further fractionation and
purification for chemical analysis and biological activity confirmation.
This process of guiding plant extract fractionation and purification by
biological activity led to the generation of PG2 from the B2 plant.
B50 is potentially the next source of a hematopoetic drug candidate.
B50 is frequently
employed in TCM. Extracts prepared
from B50 were tested both in vitro and in vivo, and had generated promising
results. These studies showed that
B50 extracts had immune potentiating activities as well as hematopoietic
stimulatory activities. The
extracts stimulated mutilineage hematopoietic recovery from radiation- or
chemotherapy-induced myelosuppression in mice and the recovery in PLTs was the
best among the three lineages. B50 extracts alleviated thrombocytopenia
associated with the therapies and promoted a much earlier recovery of PLT counts
than the control untreated mice.
Market Overview
The destruction of blood cells is a common
liability of many cancer therapies, including both chemotherapy and radiation
therapy. Unfortunately, while
killing cancer cells, these therapies kill normal cells as well, including
precursors to WBCs, RBCs and PLTs), leaving patients extremely vulnerable to
infection and anemia, as well as being prone to excess bleeding due to an
insufficiency of PLTs. Thrombocytopenia
is a common medical problem for which the main treatment is PLT transfusion.
However, PLT transfusion therapy is associated with several problems,
including refractoriness and alloimmunization, transmission of infectious
agents, and transfusion reactions. Due
to the increasing use of PLTs and the declining donor population,
PLT renewal remains an unmet medical need and identification of a safe
and effective platelet product is in high demand. Although two proteins, IL-11 (approved) and thrombopoietin
(in development) hold some promise, it is not certain that these agents will
prove to be safe and effective. Moreover,
they will share a major limiting liability -- as proteins they are expected to
be very expensive. PG50, therefore,
has been chosen as the next lead candidate in the field of hematopoiesis, with
the emphasis on PLT restoration.
PG50 in Platelet Restoration
In preliminary screening studies, extracts of
the B50 plant stimulated the in vitro production of hematopoietic cytokines by
human peripheral blood mononuclear cells as well as B2 extracts.
Furthermore, on a broad scale the hematopoietic stimulating capacity of
B50 extracts was of a similar magnitude to B2 extracts in promoting early
recovery of peripheral blood from myelosuppression in mice. In subsequent in
vitro and in vivo studies of efficacy, PG50 had both hematopoietic stimulatory
activities and immune potentiating activities.
PG50 stimulated mutilineage hematopoietic recovery from radiation- or
chemotherapy-induced myelosuppression in mice.
Among the three lineages of blood cells, the recovery in PLTs was the best.
PG50 treatment alleviated thrombocytopenia associated with the therapies and
promoted a much earlier recovery of PLT counts than the control untreated mice.
Clinical Development of PG50
The strategy for the development of PG50 will
be oriented toward potentiation of hematopoietic recovery, with an emphasis on
PLT restoration. An intravenous formulation will be developed, with the
possibility of an oral formulation for less intense, long-term administration
subsequently. Pharmagenesis will
seek a partner for later stages of development of PG50 in PLT restoration by
hematopoietic stimulation.
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