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By Biocat

The LSD molecules developed by Catalan biotechnology firm Oryzon Genomics have been shown to be effective in the treatment of acute leukemia. These were the findings of two preclinical studies directed by Dr. Arthur Zelent, from the Division of Molecular Pathology at the Institute of Cancer Research in Sutton (United Kingdom), and Dr. Tim Somervaille, of the Cancer Research UK Leukaemia Biology Laboratory at the prestigious Paterson Institute for Cancer Research de Manchester (United Kingdom).

These studies have shown that inhibiting the epigenetic target LSD1 —also known as KDM1A— is an efficient treatment for acute myeloid leukemia (AML), which makes up 40% of all leukemias in western countries, and in particular those with a certain degree of molecular reorganization (known as the MLL subtype as they involve the MLL gene).

The two British researchers concluded that there is a significant therapeutic window for the use of LSD1 inhibitors in treating these types of leukemia. According to Dr. Somervaille, the LDS1 molecule helps control the genes responsible for this type of cancer (whether or not they are activated). Furthermore, inhibiting this enzyme could block the production of proteins that lead to the disease, which is a completely new approach to treating it.

Both scientists also propose that these compounds could be used, in the future, as part of a combined cocktail of molecules to treat these hematological tumors. For example, for the APML (acute promyelocytic leukemia) subtype they suggest that a combination of all-trans retinoic acid (ATRA), a chemotherapy drug to treat this type of leukemia in patients that don’t respond to other treatments, and LSD1 inhibitors would be beneficial.

In addition to these two independent reports, research carried out by Oryzon’s own scientists point to the fact that LSD1 inhibition could also be effective in treating acute lymphoblastic leukemia (ALL), which makes up roughly one fourth of all juvenile cancers. Dr. Tamara Maes, CSO and co-founder of Oryzon, believes that "our inhibitors of LSD1 could be brought to clinical trials in leukemias and other types of cancer next year.”

The journal Science Business Exchange (SciBx), from the publishers of Nature and Biocentury, analyzed this approach in their 4 April edition, describing the company as one of the most advanced in the development of this type of molecules. Oryzon currently has an ample drug discovery program focusing on LSD1 inhibitors, with nearly 800 inhibitor molecules protected by 20 patents.

References:

Nature Medicine. 2012 Mar 11:18(4):605-11. Doi: 10.1038/nm.2661. Inhibition of the LDS1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myleloid leukemia. Division of Molecular Pathology, Institute of Cancer Research, Sutton, UK.

Cancer Cell. 2012 Mar 28. The Histone Demethylase KDM1A Sustains the Oncogenic Potential of MLL-AF9 Leukemia Stem Cells. Cancer Research UK Leukaemia Biology Laboratory, Paterson Institute for Cancer Research, University of Manchester, UK.

Related news (17/9/2012)

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