In the last
two weeks two critical papers have been published in Nature Medicine and in
Cancer CELL pointing out the role of LSD1 as a pharmacological target to treat certain
leukemias. In the CELL paper, the team from the Cancer Research UK Leukaemia,
directed by Tim Somervaille used a mouse model
of human MLL- AF9 leukemia, and
identified the lysine - specific demethylase LSD1 as an essential regulator of
leukemia stem cell potential. In a
subset of Acute Myeloblastic Leukemias, known as MLL- AF9 for the occurring molecular mutations,
LSD1 is a key effector which may be selectively targeted to produce therapeutic effect. Their
data point to a significant potential
therapeutic window for the use of LSD1 inhibitors in the MLL molecular subtype
of AML. In the experiments reported in
this paper Somervaille’s team was using LSD1 inhibitors described in Oryzon’s
patents. In the Nature’s paper, the lead team of the Division of Molecular
Pathology, Institute of Cancer Research, Sutton UK, directed by Anthony Zelent in collaboration with other labs identify LSD1
as a therapeutic target and for AML pathogenesis and show that the combination
of LSD1 inhibition with treatment with all-trans retinoic acid greatly enhance
the therapeutic response.
One of the
needs for any drug is to find those diseases or subset of diseases where the mechanism
is more efficient. It has been proven now that certain leukemias are the first target
for LSD1 inhibitors. However, due to its high level expression, LSD1 has been suggested also as a therapeutic
target in other types of cancer as poor- risk
prostate adenocarcinoma ( Kahl et
al., 2006), poorly differentiated neuroblastoma (Schulte et al., 2009) and high
grade ER negative breast cancer (Lim et
al., 2010).
Oryzon has
been producing in the last years almost 800 different compounds that are
extremely potent (in the low nanomolar range) and with excellent
pharmacological properties. We have also seen significant tumor reduction in
several animal models like acute lymphoblastic leukemia and breast cancer and our CSO, Dr. Tamara Maes was a few weeks ago presenting our program at the 4th Annual CHI X-Gen Congress, in the CLINICAL GENOMICS. Epigenetics, Targets and Therapies in San Diego, California. This program is
covered by a set of 20 patent applications giving us a dominant IP position in
the field. We are confident that our molecules will have a role in the future
in the therapies designed for these devastating diseases.
