With this in mind, Joanna Collingwood, from the Institute for Science and Technology in Medicine at Keele University, UK, and Mark Davidson from the University of Florida (Gainesville, FL) are employing synchrotron techniques to investigate the distribution and form of metal ions in brain tissue at the cellular level, with particular emphasis on elevated iron concentrations. Their studies revealed that the distribution of metal ions in the brain tissue of Parkinson's sufferers is altered by the disease process.
The research was performed at Diamond - the UK's national synchrotron - using a technique called microfocus spectroscopy, in which high-power, tightly focussed X-rays beams penetrate tissue samples. By examining the tissue as a whole, the researchers mapped the metal distribution throughout the part of the brain containing the vulnerable motor neurones in Parkinson's disease. Earlier studies have shown that iron levels in individual cells nearly double in this region.
"We have been able to investigate human tissue with such precision that metal ions, particularly iron levels, in and around individual cells can be mapped," said Collingwood, who presented the results at the American Association for the Advancement of Science Meeting, held last week in Chicago, IL. "What makes the microfocus synchrotron approach so unique is that we can also use the focussed beam to obtain information about the form in which the iron is stored."
Another important advantage of this technique is that it does not change the distribution or form of the metals in the tissue being studied - a feature Collingwood attributes to "years of work on optimizing the tissue preparation method".
To move this research into the clinical arena, Collingwood and Davidson must now determine how much of the contrast change observed in MRI scan results is directly due to the changes in iron distribution and form seen in the Diamond studies. To that end, they are working closely with researchers at the University of Florida's McKnight Brain Institute on studies of MRI for early diagnosis.
"Early diagnosis is key because we know that by the time a typical individual presents with the symptoms of the disease, chemical changes have already caused significant cell death of vulnerable motor neurones," said Collingwood. Early detection of disease could also enable the use of chelation-based therapies (removing or inactivating metals in the body) before patients experience irreversible cell loss.
In the case of Parkinson's disease, a targeted chelation approach is necessary, as local regions are affected rather than the overall systemic iron levels being elevated. The knowledge obtained by the synchrotron techniques could thus prove critical to the design of appropriate treatments.