By A.C. Woolnough
Researchers work on some incredible projects as they toil in relative obscurity in their cramped, underfunded labs trying to unlock the mysteries of the brain and neurological diseases like Parkinson’s. Fortunately, the National Institute of Health, the Department of Defense, universities and various foundations are underwriting the costs of this exacting and time-consuming research with no guarantee of success. Unfortunately, less than one quarter of proposed projects ever make it through the competitive funding process.
I’m not a molecular biologist, brain surgeon or biochemist, but as a PWP (person with Parkinson’s) I do have a curiosity about what these graduate students, PhDs, and MDs are doing to help identify causes, treatments and the magic bullet — a cure! To learn more, I have participated in studies at the Columbia University Neurological Institute, reviewed Parkinson’s research grant proposals and met with scientists to evaluate and score other PD projects. What follows is a layman’s understanding of some of the more fascinating — sometimes unusual or seemingly bizarre — ideas being pursued. I must admit, my biggest disappointment was seeing they don’t wear white lab coats and skulk around with hunched backs and diabolical accents. Any errors of fact are mine!
Nevertheless, much of the current research seems lifted right out of science fiction. For example, using viruses with fragments of DNA attached, scientists inject these nanoparticles into the brain—to (hopefully) stimulate or restore neuronal (brain cell) activity in certain areas of the brain. One reason for using nanoparticles is the wonderful defense mechanism we have called the blood-brain barrier (BBB) which acts as a filter to keep out most molecules (especially potentially toxic substances) from entering the brain. Opioids and cocaine, however, have no problem crossing the BBB—with mixed results for society.
One of my favorite avenues being explored in multiple labs takes a bit of explaining. Apparently, it is possible to genetically alter mice (with jellyfish DNA) so their brain cells will fluoresce when activated. Researchers then shave their little mouse heads, carefully remove the top of their skull and glue on a little glass plate—a window into their brain. Of course, there is a technical term for this: in vivo multiphoton fluorescence microscopy through “cranial windows.” The mice are then injected with a chemical that simulates Parkinson’s disease. While strapped into a little harness and running on a treadmill, scientists use highly specialized microscopes to observe what areas of the brain are firing and which are not. Then, various treatments (drugs) can be tested to see if they improve brain function and movement. Involuntary muscle contractions (for example, tremors and freezing) are common with PWPs which is what makes this research so exciting.
For those readers who don’t like the idea of using mice, researchers also use drosophila—more commonly known as fruit flies. Because they have tiny little brains (still very sophisticated) scientists have been able to map essentially every neuron and know its function. These little buggers (pun intended!) can be genetically modified or studied as to the effects of various chemicals—both as potential causes of brain dysfunction and potential treatments for neurological deficits.
Another avenue of research involves using young zebrafish. These little swimmers also have a relatively simple nervous system but with the advantage of being transparent for a few weeks. Scientists can look directly into the brains of these creatures while still alive. As a good scientist, however, we realize the downside of utilizing these fish. First, as they grow up, they lose their transparency. Second, Parkinson’s takes years to develop; a short window of opportunity with these fish does not make a great model for PD. Finally, fish are neither hominids or even mammals and research on fish does not necessarily translate to humans—another reason why mice are a better, though imperfect, model. No animal “gets” actual Parkinson’s which is one more reason why research is so challenging.
A final example of cutting-edge research involves the creation of brain sims—three dimensional clumps of living neurons mimicking actual brains—or, at least a functioning neural network. Sophisticated study and analysis of neuronal interaction at the molecular level leads to a better understanding of brain function (and dysfunction) — with the potential for development of new or better treatments. This is fundamental, basic science at its best.
I would like to personally thank all the dedicated scientists and researchers working so hard (with little appreciation) for people they don’t know and will probably never meet. I was delighted to have an hour-long conversation over lunch with one such young scientist (who had never met a PWP) at Columbia University. We both came away feeling we had gotten the better result from our time together. She learned what it was like to live with PD, and I got to experience a true hero: a PD researcher.
After being diagnosed with Parkinson’s Disease, A.C. is calling on his 37 years in K-12 education to became a “Parkinson’s Warrior” by educating the public, advocating for a cure and participating in research.