Richard Wilson, another close friend from our support group, died the week before. We often went to lunch at the Politics & Prose bookstore café after our meetings.
About a dozen people typically attend those weekly meetings. One member has been dealing with dementia for several years. Now, two others are clearly slipping into the fog. I wrote recently about recent studies confirming that dementia and cognitive impairment often go hand-in-hand with Parkinson's.
Today our latest spell of heat and humidity broke, and I got to spend much of the day in the back porch rocking chair. FedEx brought me a package with two good-sized koi for the pond. (Is there anything we can't order online these days?)
I want to continue this upbeat turnaround with tonight's post. I remembered a New York Times piece (shown below) in my files by Jon Palfreman, professor of broadcast journalism at the University of Oregon. Palfreman is also the author of the forthcoming book "Brain Storms: The Race to Unlock the Mysteries of Parkinson's." I just pre-ordered it on Amazon.com.
Can Parkinson’s be slowed, stopped or even reversed? Can the disease be prevented before it starts, like polio and smallpox? More than at any time in history, success seems possible.
Having sequenced the human genome, biomedical researchers have now set their sights on the ultimate frontier — the human brain. The formidable puzzle is to figure out how a three-pound lump of mostly fatty matter enables us to perform a seemingly endless number of tasks, like walking, seeing, hearing, smelling, tasting, touching, thinking, loving, hating, speaking and writing ... and why those awesome abilities break down with neurological disease. Many scientists view Parkinson’s as a so-called pathfinder. If they can figure out what causes Parkinson’s, it may open the door to understanding a host of other neurodegenerative diseases — and to making sense of an organ of incredible complexity.
In Parkinson’s, the circuitry in a tiny region of the brain called the basal ganglia becomes dysfunctional. Along with the cerebellum, the basal ganglia normally acts as a kind of adviser that helps people learn adaptive skills by classic conditioning — rewarding good results with dopamine bursts and punishing errors by withholding the chemical. Babies rely on the basal ganglia to learn how to deploy their muscles to reach, grab, babble and crawl, and later to accomplish many complex tasks without thinking. For example, when a tennis player practices a stroke over and over again, the basal ganglia circuitry both rewards and “learns” the correct sequence of activities to produce, say, a good backhand drive automatically.
But this brain circuit has a vulnerability: It depends on dopamine. When the production of dopamine is interrupted, as it is with Parkinson’s, the signals passing through the basal ganglia are garbled, and it ends up giving poor advice. Corrupted signals pass to other brain regions such as the thalamus (which relays sensory and motor data) and the cortex (which is responsible for many higher functions such as language and consciousness). These bad signals disrupt communication between the brain and the muscles. This is one reason people with Parkinson’s have trouble picking up small objects and moving around fluently: Their motions are too hesitant, too small, too slow, too rigid, too shaky, too feeble and badly timed. These are symptoms of a brain in conflict with itself.
Having Parkinson’s feels a bit like going on vacation in another country and having to drive on the “wrong” side of the road. Driving is one of those activities that we outsource, in large part, to the basal ganglia. When an American, who has spent thousands of hours driving on the right side of the street, tries to drive in England, his learned habits are a liability. To compensate, he must invoke the deliberate and goal-directed part of his brain — the cortex — to override the basal ganglia. The driving will be difficult, partly because the conscious brain is now doing all the work, but mainly because it’s having to compensate for signals from the basal ganglia that are inappropriate for the situation at hand.
But why is the production of dopamine interrupted in the first place?
That may come down to the behavior of a common protein called alpha-synuclein. This molecule’s importance for Parkinson’s was discovered over 20 years ago, when the New Jersey neuroscientist Lawrence Golbe stumbled across two patients who were descendants of an extended family originally from the Italian village of Contursi. This family was cursed with a very rare genetic form of Parkinson’s; family members had a 50 percent chance of inheriting the disease,
Subsequent research found that those affected carried a mutated gene on Chromosome 4 that coded for alpha-synuclein.
While Parkinson’s disease is not usually inherited like this, the discovery provided a vital clue about the way Parkinson’s typically worked. Most patients do not have this mutation, but they do, it turned out, have sticky deposits of alpha-synuclein inside their brains, found when they were examined post-mortem. This protein seems to be an integral part of the disease that affects all Parkinson’s patients.
Here’s the theory scientists have come up with: Sometimes good proteins go bad. For multiple reasons (like genes, environment and age) proteins can “misfold” and stick to other proteins. When proteins do this, they can become toxic, capable of jumping from cell to cell, causing other alpha-synuclein proteins to do the same and potentially killing neurons (especially dopamine-producing ones) in their wake. This process is not confined to Parkinson’s disease. Misfolded proteins appear to be implicated in other devastating neurological disorders such as Alzheimer’s disease, Huntington’s disease, Lou Gehrig’s disease and Creutzfeldt-Jakob disease — a human variant of mad cow.
What can be done about such badly behaving proteins? Cells possess an elaborate series of control mechanisms to help proteins behave correctly and to destroy and recycle them if they don’t. But these controls are not perfect. As human life spans increase so, too, does the likelihood of protein malfunctioning that could lead to neurological disease.
So patients like me are looking to neuroscience research to lend nature a helping hand. And remarkably, some researchers foresee the possibility that one day in the not too distant future they may be able to develop drugs to target these rogue proteins, potentially combating several neurological diseases in one go.
An American biotech company, NeuroPhage, for example, plans to enroll Alzheimer’s and Parkinson’s patients in 2016 and 2017 in Phase 1 trials of its new product, a genetically engineered compound derived from a naturally occurring virus called M13. Researchers have demonstrated that this compound can enter rodents’ brains and neutralize toxic clumps of alpha-synuclein and the corresponding targets for Alzheimer’s (the proteins amyloid beta and tau). The question is, will it work as well in people’s brains? And will it arrest or reverse patients’ symptoms?
People with Parkinson’s progressively lose core pieces of themselves. We forget how to walk. Our arm muscles get weaker. Our movements slow down. Our hands fumble simple tasks like buttoning a shirt or balancing spaghetti on a fork. Our faces no longer express emotions. Our voices lose volume and clarity. Our minds, in time, may lose their sharpness and more. But unlike many cancer victims, people with Parkinson’s tend to survive for a long time. And unlike Alzheimer’s or Huntington’s patients, many of us can report lucidly on our condition until the end. Parkinson’s patients like me take comfort from the idea that our insights can help unpack these diseases and assist in the scientific pursuit of better therapies and ultimate cures.