Seeking New Method to Treat Leukemia
August 29, 2013
Researchers at the University of £ód¼ in central Poland are studying compounds known as fourth-generation dendrimers, which they hope will lead to a new way of treating patients with lymphocytic leukemia.
Chronic lymphocytic leukemia is the most common type of leukemia occurring mostly in adults over 60 years of age. This represents 25-30 percent of all forms of leukemia. However, these days the disease increasingly affects young people as well.
The bone marrow of a person with chronic lymphocytic leukemia produces a huge number of leukemia cells. There may be as many as 200,000 of them, and they are all virtually immortal. Any normal, healthy cell has its own biological clock, as a result of which, after some time, 10 days, for example, the cell succumbs to the so-called apoptosis mechanism, or programmed cell death. When it dies, it is excreted into the spleen and destroyed there. New, young cells come in its place.
The method developed by the £ód¼ researchers, including Ida Franiak-Pietryga, Ph.D. ,offers hope that doctors will finally be able to control the production of leukemia cells by the bone marrow. Franiak-Pietryga is conducting her research in the Laboratory of Clinical Immunology, Transplantation and Genetics at the Nicolaus Copernicus Provincial Specialist Hospital in £ód¼. There she has come into contact with cases of the disease in patients in their 20s. She has studied the genetic mechanisms of leukemia since 2007.
Currently, the only method used in treating leukemia is chemotherapy and until the end of their lives patients have to take expensive drugs that inhibit the proliferation of diseased cells.
Wondering how “immortal” leukemia cells could be cheated and killed, Franiak-Pietryga says she came up with the idea of using dendrimers for this purpose. These are manmade, nanoscale compounds with unique properties that make them useful to the health and pharmaceutical industry as both enhancements to existing products and as entirely new products. Dendrimers—the name derives from the Greek dendron, or tree—have a tree-like structure. They are highly branched, star-shaped macromolecules with nanometer-scale dimensions. They are constructed by the successive addition of layers of branching groups. Each new layer is called a generation. The final generation incorporates the surface molecules that give the dendrimer the desired function for pharmaceutical, life science, chemical, electronic and materials applications. Dendrimers fall under the broad heading of nanotechnology, which covers the manipulation of matter in the size range of 1-100 nanometers (one million nanometers equal one millimeter) to create compounds, structures and devices with novel, pre-determined properties.
Dendrimers were first described in 1983 as spherical nanoparticles 2 to 10 nanometers in size that can connect more layers to their core.
Dendrimers are increasingly being studied for use in medicine. A University of £ód¼ team led by Prof. Maria Bryszewska has been studying various dendrimers for more than 10 years.
A scientist can adapt the structure of a dendrimer to his or her needs, says Franiak-Pietryga, adding that “bare” dendrimers are highly toxic, killing everything in their path. Researchers aim to reduce the toxicity, encasing the dendrimers with various chemical compounds. Franiak-Pietryga says she has used dendrimers “coated” with sugar—produced at the Institute of Polymer Research in Dresden, Germany, and based on an idea by Dr. Dietmar Appelhans—in her research.
“So far only trials in which dendrimers were used as drug carriers were conducted,” Franiak-Pietryga says. “Our project is innovative in that it uses dendrimers as active substances in their own right. The chemical modification, or coating, made it possible to preserve their efficiency while reducing the unwanted toxicity. We have conducted our in vitro studies on chronic lymphocytic leukemia cells.”
Earlier, the team led by Bryszewska, which Franiak-Pietryga joined at one point, conducted studies on healthy rats. It turned out that dendrimers did no harm to the animals as the compounds were excreted through the kidneys, Franiak-Pietryga says. Now the researchers plan to conduct research to see how dendrimers will behave in the bodies of animals with leukemia.
With fourth-generation dendrimers, leukemia cells that were so far considered to be immortal begin to die, Franiak-Pietryga says. Regardless of whether they get inside or just come into contact with the diseased cell, they initiate the apoptosis process. The research has shown that 80 to 90 percent of these cells perish.
The fourth-generation dendrimers developed at the University of £ód¼ won a gold medal at this year’s 12th Concours Lépine international invention fair in Paris after they were entered for the competition by the university’s Center for Technology Transfer.
Danuta K. Gruszczyńska