LSD1 is a target in Acute Myeloid Leukemia

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.