18 May 2012

Will "uncharged" nanoparticles cure autoimmune diseases?

A delivery system for gene therapy may help in the treatment of arthritis

Nanonewsnet based on materials from Georgia Health Sciences University:
Delivery system for gene therapy may help treat arthritis

A DNA-coated submicroscopic bead used to deliver genes and drugs to cells has proven to have therapeutic value in itself. A few hours after the introduction of DNA-coated nanoparticles that do not carry any payload, scientists at the Georgia State University of Medicine (GHSU) were surprised to note an increase in the expression of an enzyme that "calms" the body's immune response.

According to scientists who published a report on their study in The Journal of Immunology (Engineering DNA Nanoparticles as Immunomodulatory Reagents that Activate Regulatory T Cells), in an animal model of rheumatoid arthritis – a severe autoimmune disease – increased expression of the enzyme indolamine-2,3-dioxygenase (indoleomine 2,3 dioxygenase, or IDO) significantly mitigates the signs of edema and inflammation of the joints of the extremities.

In 1998, Andrew Mellor and David Munn reported in the journal Science that the enzyme IDO is expressed by the fetus – to avoid rejection by the immune system of the maternal body. Subsequent studies have shown that tumors also use IDO for protection, and clinical studies of the antitumor potential of IDO inhibitors are now underway. On the other hand, there is evidence that increased expression of IDO can protect transplanted organs from immune attack.

"It's like pouring water on fire," says study leader Dr. Andrew L. Mellor, director of the GHSU Medical College. "The fire burns the house, in this case, the tissue that is necessary for the normal functioning of the joints," he describes the unexplained attack of the immune system on bone shock absorbers – cartilage. "High levels of IDO seem to give us more water to tame this fire."

Several systems are used to deliver genes to cells in the treatment of diseases such as cancer, HIV infection and Parkinson's disease by gene therapy methods. The results obtained recently suggest that the DNA nanoparticle method is also successfully applicable to autoimmune diseases such as arthritis, type 1 diabetes and lupus.

"We want to stimulate the production of IDO, as this enzyme protects healthy tissue from destruction by the immune system," Dr. Mellor continues.

Scientists were studying the potential of treating autoimmune diseases by embedding the human IDO gene into DNA nanoparticles, hoping to increase the expression of IDO in their model of arthritis. However, by a happy coincidence, the first author of the article, Dr. Lei Huang, discovered that DNA nanoparticles themselves cause the desired effect. How and why is still being studied. Preliminary data suggest that immune cells phagocytes, white blood cells that absorb unwanted bacteria and dying cells, begin to produce more IDO in response to the DNA nanoparticle.

"Phagocytes eat and react quickly to it, and the effect we get is IDO," explains Dr. Mellor.

Co-author of this study, immunologist Tracy McGaha, PhD, recently found that such cells prevent the development of systemic lupus erythematosus in mice. The studies planned for the near future will include documenting all cells that respond by increasing IDO synthesis.

The polyethylenimine used in this study is not biodegradable, but scientists need one that eventually breaks down in the body without having a toxic effect. In addition, they would like to get their hands on a material that could target specific cells, for example, located near inflamed joints, in order to minimize any potentially harmful side effects.

To find the optimal polymer, scientists from GHSU have already organized cooperation with specialists in the field of biopolymers from the Massachusetts Institute of Technology (Massachusetts Institute of Technology), the University of California at Berkeley (University of California, Berkeley) and the Georgia Institute of Technology (Georgia Institute of Technology).

While in this case DNA should not be solely responsible for getting the desired response, it is necessary to make cells express IDO. To be completely sure that IDO expression is responsible for improving the condition, the scientists conducted experiments on mice that had an IDO inhibitor added to drinking water, and on genetically modified mice with a suppressed IDO gene.

"Without access to the IDO molecular pathway, this therapy doesn't work," Mellor sums up.

Portal "Eternal youth" http://vechnayamolodost.ru18.05.2012

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