A lipid in avocados that combats acute myeloid leukemia (AML) has been discovered by a University of Waterloo professor. It fights AML by targeting the root of the disease, leukemia stem cells.
Currently, there are few drug treatments available to patients that target leukemia stem cells.
Acute myeloid leukemia is a type of cancer in which the bone marrow makes abnormal myeloblasts, red blood cells, or platelets. It proves fatal within five years for 90 per cent of seniors over age 65.
The new avocado-derived drug could one day significantly increase life expectancy and quality of life for AML patients, said Professor Spagnuolo:
“The stem cell is really the cell that drives the disease. The stem cell is largely responsible for the disease developing and it’s the reason why so many patients with leukemia relapse. We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets stem cells selectively, leaving healthy cells unharmed."
Abnormal Stem Cells
In AML, the myeloid stem cells usually become a type of immature white blood cell called myeloblasts (or myeloid blasts). The myeloblasts in AML are abnormal and do not become healthy white blood cells.
Sometimes in AML, too many stem cells become abnormal red blood cells or platelets. These abnormal white blood cells, red blood cells, or platelets are also called leukemia cells or blasts.
Leukemia cells can build up in the bone marrow and blood so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or easy bleeding may occur. The leukemia cells can spread outside the blood to other parts of the body, including the central nervous system (brain and spinal cord), skin, and gums.
Through partnership with the Centre for Commercialization of Regenerative Medicine (CCRM) Spagnuolo has also filed a patent application for the use of the compound, named avocatin B, to treat AML.
“It’s an exciting time for our lab. With the help of CCRM we are now pursuing commercial partnership that would take avocatin B into clinical trials,” said Professor Spagnuolo. “Not only does avocatin B eliminate the source of AML, but its targeted, selective effects make it less toxic to the body, too."
The drug is still years away from becoming approved for use in oncology clinics, but Spagnuolo is already performing experiments to prepare the drug for a Phase I clinical trial. This is the first round of trials where people diagnosed with AML could have access to the drug.
There are multiple potential applications for Avocatin B beyond oncology, and the drug is just one of several promising compounds that Spagnuolo and his team have isolated from a library of nutraceuticals. Most labs would use food or plant extracts, but Spagnuolo prefers the precision of using nutraceuticals with defined structures.
“Extracts are less refined. The contents of an extract can vary from plant to plant and year to year, depending on lots of factors - on the soil, the location, the amount of sunlight, the rain,” said Spagnuolo. “Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics."
Professor Spagnuolo is among only a handful of researchers worldwide, applying the pharmaceutical industry’s rigorous drug discovery research processes to food-derived compounds, called nutraceuticals.
Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death Eric A. Lee, Leonard Angka, Sarah-Grace Rota, Thomas Hanlon, Andrew Mitchell, Rose Hurren, Xiao Ming Wang, Marcela Gronda, Ezel Boyaci, Barbara Bojko, Mark Minden, Shrivani Sriskanthadevan, Alessandro Datti, Jeffery L. Wrana, Andrea Edginton, Janusz Pawliszyn, Jamie W. Joseph, Joe Quadrilatero, Aaron D. Schimmer, and Paul A. Spagnuolo Cancer Res June 15, 2015 75:2478-2488; doi:10.1158/0008-5472.CAN-14-2676