If you talk about curing smallpox, I know what you mean. You mean that a person might have the smallpox virus in his or her body, and you want me to make a drug that removes it. I can visualize that: we need a chemical that will bind to the smallpox virus and activate the body's own systems for getting rid of stuff. If you have cancer and talk about curing cancer, I know what that means: it means that you have some cells that carry mutated DNA that makes them cancerous, and you want me to get rid of those cells.
When we talk about a cure for Parkinson's, I don't think we all mean the same thing.
When you have Parkinson's, neurons in your brain get sick. They stop working the way that they should. The connections they make with other cells atrophy and disappear. Eventually, the neurons die. To be diagnosed with Parkinson's disease, you very likely have many neurons dead and gone. (We all lose neurons as we age, just with Parkinson's some specific ones die faster.) Other neurons get sick and atrophy, losing the connections that are central to brain function.
If a cure for Parkinson's means restoring the brain (motor? cognitive?) function to a level of functioning that is typical of people of the same age, sex, education, and activity level, that isn't a cure like a cure for smallpox or a cure for cancer. It isn't just removing the other -- for example, a virus or defective cells. It is removing an other -- misfolded forms of a protein -- and also replacing lost function.
Thus, mechanistically there is no way that one therapy would achieve both results -- stopping the pathology and replacing lost function.
We are pretty close to stopping the pathology. There are trials right now (May 2015; EDITED 10/19/2015 -- the trial lined under the word "trial" has had very positive results published) hoping to stop or slow Parkinson's pathology. Each of these is based on a good understanding of basic biology and/or population studies. Each of these studies promises to at least shed new light on Parkinson's disease, even if they don't directly lead to a therapy. It is worth noting that even a failed therapy provided the new insight to put us on track to today's most promising therapeutic targets.
In terms of replacing lost function, dopamine replacement therapy is the gold standard and represented a revolution in Parkinson's treatment that won its developers the Nobel Prize. We can do pretty well at replacing dopamine. We do much worse at restoring the function lost as other systems are attacked by Parkinson's. Cell-based therapies, despite the hype and enthusiasm, don't work in controlled trials. Outliers seem to benefit, but not better than outliers in studies of medical therapy.
The future of Parkinson's is most likely this: we will develop therapies that stop the progression, with some recovery of atrophied neurons (leading to some recovery-related dyskinesia and possibly hallucinations). Lost neurons will not recover. Once we can stop the pathology of Parkinson's disease, we will treat people at their earliest signs and we will be done with Parkinson's.
As far as restoring lost function, we do really well with medication today. As far as cellular solutions, if we could replace the lost cells in Parkinson's disease, we could replace the lost cells with natural aging. It would be a fountain of (brain) youth. We're probably not there yet. Your brain ages for an evolutionary reason, and I don't think we're quite there in reversing this yet.
The change in our mental models of Parkinson's from being a disease of dopamine to being a disease of alpha synuclein have changed the meaning of cure. I can imagine stopping the pathology of alpha synuclein, thus curing Parkinson's. However, having cured the disease of alpha synuclein, people will still have symptoms of their alpha synuclein disease that linger on, for example, their lost dopamine cells. A cure for the underlying pathology of Parkinson's won't eliminate the burden of the disease -- people will probably still need their sinemet -- but it will change our view of the future for people with the disease.
Thus, mechanistically there is no way that one therapy would achieve both results -- stopping the pathology and replacing lost function.
We are pretty close to stopping the pathology. There are trials right now (May 2015; EDITED 10/19/2015 -- the trial lined under the word "trial" has had very positive results published) hoping to stop or slow Parkinson's pathology. Each of these is based on a good understanding of basic biology and/or population studies. Each of these studies promises to at least shed new light on Parkinson's disease, even if they don't directly lead to a therapy. It is worth noting that even a failed therapy provided the new insight to put us on track to today's most promising therapeutic targets.
In terms of replacing lost function, dopamine replacement therapy is the gold standard and represented a revolution in Parkinson's treatment that won its developers the Nobel Prize. We can do pretty well at replacing dopamine. We do much worse at restoring the function lost as other systems are attacked by Parkinson's. Cell-based therapies, despite the hype and enthusiasm, don't work in controlled trials. Outliers seem to benefit, but not better than outliers in studies of medical therapy.
The future of Parkinson's is most likely this: we will develop therapies that stop the progression, with some recovery of atrophied neurons (leading to some recovery-related dyskinesia and possibly hallucinations). Lost neurons will not recover. Once we can stop the pathology of Parkinson's disease, we will treat people at their earliest signs and we will be done with Parkinson's.
As far as restoring lost function, we do really well with medication today. As far as cellular solutions, if we could replace the lost cells in Parkinson's disease, we could replace the lost cells with natural aging. It would be a fountain of (brain) youth. We're probably not there yet. Your brain ages for an evolutionary reason, and I don't think we're quite there in reversing this yet.
The change in our mental models of Parkinson's from being a disease of dopamine to being a disease of alpha synuclein have changed the meaning of cure. I can imagine stopping the pathology of alpha synuclein, thus curing Parkinson's. However, having cured the disease of alpha synuclein, people will still have symptoms of their alpha synuclein disease that linger on, for example, their lost dopamine cells. A cure for the underlying pathology of Parkinson's won't eliminate the burden of the disease -- people will probably still need their sinemet -- but it will change our view of the future for people with the disease.
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