Can anything be done about Parkinson’s Disease?
[Editor’s note: IEET columnist and transhumanist Dick Pelletier died from Stage 5 Parkinson’s not that long ago. There has been much progress but many lives still continue to be lost. Support Parkinson’s research and related scientific funding.]
There’s nothing that will help everyone.
But there’s probably something that will help you.
This is the emerging paradigm of individualized medicine. We are in transition from a past when we looked for “the cure” (antibiotics, vaccines) that would work universally to a future in which blood tests and computer analysis will determine exactly the right treatment for your individual metabolism. While in that in-between space, the key will be personal experimentation. Seek out reports of “miracle cures” in which something worked spectacularly well for just a few patients, while failing to help the others. Find ten such miracles, and try them on yourself, one at a time. Experiment to see what works for you.
Today’s column is motivated by news I received Friday about a long-time friend whose Parkinson’s is creeping out from medical control. At 68, George is active and young in outlook.
Symptoms of PD include tremors, slow and uncertain movements, loss of motor control, shuffling. There often is cognitive impairment, especially at later stages.
The cause of PD is the loss of neurons in a particular region of the mid-brain called the substantia nigra (SN), where nerve signals are translated into chemical signals. One of the functions of these nerve cells is to secrete dopamine, a neurotransmitter.
We’re all losing neurons, but we don’t all have symptoms. Maybe at age 50 our hand isn’t quite as steady as it was at age 30, but it’s nothing we would talk to a doctor about. By the time “symptoms” appear, over 70% of the dopaminergic neurons are gone.
It is agreed that the cause of PD is the loss of these nerve cells. We might assume from the fact that that they are nerve cells in the brain that they perform their secretion function in a way that is smart, in response to activity and stimuli. And yet, the standard medical treatment for Parkinson’s does not address the loss of this population of nerve cells, with the many functions they perform, nor does it even attempt to deliver dopamine in a smart and targeted way. The best treatment medicine has to offer is to flood the brain with supplementary dopamine.
A few decades ago, it was thought that no new nerve growth takes place in the brain after adolescence. We now realize that nerve growth continues lifelong, although neurogenesisslackens with age and does not keep up with nerve loss. There are stem cells in the brain, and these can mature as neurons, or as glial cells or astrocytes that contribute vitally to brain chemistry.
A real cure for PD would be to re-grow the lost nerve cells of the SN. Why not use stem cell therapy to regenerate the nerves? This was a promising line of research about a decade ago [in rats, in people]. But when stem cells were injected into the brains of Parkinson’s patients, they withered on the vine. They were perfectly good stem cells, but something was telling them to slack off.
This is the converse of a theme that researchers have encountered in many contexts. Put an old cell in a young environment, and it acts young; conversely, put a young cell in a old environment and it acts old. There are signal molecules–presumably carried in the blood plasma–that carry messages about age. (This leads us back to the work of Amy Wagers and Mike and Irina Conboy and Tom Rando and Saul Vileda and Tony Wyss-Coray, all building a foundation for anti-aging therapies based on blood factors. I have repored on the subject here, here, and here.)
Although enthusiasm has waned for stem cells as a one-stop cure for PD, the research community is continuing to refine the technology. A transition is in effect from fetal stem cells, limited in availability by Bush-era regulations, to stem cells derived from the patient’s own cells, which have the advantage of being a perfect genetic match. Stem cells do not have to be injected into the brain, because they have a remarkable ability to find their way to the place they are needed. The most effective delivery at present is through the nose, or (more invasive) guided via a catheter that is threaded through arteries that lead to the brain.
Cell Senescence and PD
Are the lost brain cells that cause PD dying simply because their telomeres run out? This would not seem a likely connection to make, since telomeres shorten with cell replication, and in the brain, cell replication is slow compared to blood, skin or even muscle cells. But in a new article from Buck Institute last week, Megumi Mori reviews an unexpected connection between cell senescence and PD, documented by Judy Campisi’s research group. Astrocytes are star-shaped glial cells, the background support substrate for the brain which create the proper chemical environment for neurons. Astrocytes grow and are replaced continually during a lifetime, and hence their telomeres shorten with age. Aging astrocytes become senescent cells, and secrete inflammatory toxins–the so-called Senescent-Associated Secretory Phenotype, or SASP. Senescent astrocytes and these toxins have been linked to PD.
What can be done to prevent and to treat Parkinson’s Disease?
Returning to the theme at the top of this page, I ask what options can people try to prevent PD or to slow its progression.
- Selegiline (aka deprenyl, or Emsam) was a standard treatment for PD in the 1980s. It has since fallen out of favor because of inconsistent results, but I think it deserves consideration and personal experimentation, especially since there are no outstanding alternatives. Selegiline acts in two ways, addressing both the symptom and cause of PD. Its primary action is an MAO-B inhibitor, which slows the chemical breakdown dopamine, so that the existing dopamine remains available longer*. Secondarily, Selegiline is neuroprotective.
The main reason I am enthusiastic about Selegiline is because of its potential as a life extension drug. Selegiline is on the short list of drugs that have succeeded in extending life span of rodents. [my blog in the subject from 2 years ago]
- Stem cell therapies are working well for some patients, and new experiments are likely to make the treatment more effective for more people.
- Glutathione (standard abbreviation=GSH) is the only one of the body’s natural anti-oxidants that I believe has anti-aging potential. Levels decline with age. GSH depletion is both a cause and an effect of the loss of neurons in the SN [ref, ref].
GSH is a short protein molecule, a tripeptide. It does not survive digestion in the stomach, but the molecule is small enough that with finesse it can be delivered orally. There are new products with liposomal encapsulated GSH that purport to survive the stomach so that more GSH is delivered to the bloodstream. GSH can also be absorbed in a nasal spray. A more traditional product is to ingest N-Acetyl Cysteine (NAC) which is a precursor to GSH.
I have a friend, a vibrant 86-year-old MD who tells me he has a Parkinson’s tremor which is well managed and controlled with liposomal glutathione. One small study of intravenous GSH for Parkinson’s showed inconsistent benefits that were not statistically significant overall, but might be interpreted as promising for a larger study.
- There is anecdotal evidence for benefits for PD from telomerase therapy (cycloastragenol, TA65, Product B, etc). No study has been done. Here is a video from Ed Park.
- Most people living above the tropics don’t get enough vitamin D. There are large individual differences in absoption and need for Vit D. Low vitamin D levels arestatistically associated with Parkinson’s. [another ref]
- Exercise is good for every aspect of aging, including PD.
- Rapamycin is a powerful anti-aging drug with powerful side effects. It has been effective in vitro and in preliminary animal trials against Parkinson’s. It is probably a powerful neuroprotector, and has been proposed for trials delaying progression of PD.
- Melatonin might help some people.
- Curcumin (from turmeric) has been used with some success.
- It’s a long shot, but Magnesium Threonate might be neuroprotective.
- If you are taking statin drugs, consider alternative means to lowering your risk of heart disease. Statins double the risk of PD.
- Not to harp on the issue, but intermittent fasting and caloric restriction are powerfully neuroprotective. This article from Johns Hopkins Med School reviews the evidence.
Researchers at the National Institute on Ageing in Baltimore said they had found evidence which shows that periods of stopping virtually all food intake for one or two days a week could protect the brain against some of the worst effects of Alzheimer’s, Parkinson’s and other ailments.
“Reducing your calorie intake could help your brain, but doing so by cutting your intake of food is not likely to be the best method of triggering this protection. It is likely to be better to go on intermittent bouts of fasting, in which you eat hardly anything at all, and then have periods when you eat as much as you want,” said Professor Mark Mattson, head of the institute’s laboratory of neurosciences.
Cutting daily food intake to around 500 calories – which amounts to little more than a few vegetables and some tea – for two days out of seven had clear beneficial effects in their studies, claimed Mattson, who is also professor of neuroscience at the Johns Hopkins University School of Medicine in Baltimore.
…the growth of neurones in the brain could be affected by reduced energy intakes. Amounts of two cellular messaging chemicals are boosted when calorie intake is sharply reduced, said Mattson. These chemical messengers play an important role in boosting the growth of neurones in the brain, a process that would counteract the impact of Alzheimer’s and Parkinson’s. [The Guardian]
Experimenting on yourself–the one-person trial is the only one that matters
If you have Parkinson’s Disease or Parkinsonism or early Parkinson’s symptoms, then each one of the above suggestions offers some small chance of improving your condition. Start by keeping a daily diary of symptoms, a baseline of at least two weeks. Then try the above suggestions, one at a time. Continue the diary so you can look back and determine what works and what doesn’t. If you believe you have found a benefit, go off the treatment for a week, then back on, to see if your diary reflects a response to the treatment, or if it was just a fluke.
Don’t give up. It is unlikely that any given treatment will work for you, but it is likely that patience and persistence and controlled experimentation will be rewarded with something that helps.
* Dopamine, like all neurotransmitters and many other hormones, is continually being manufactured and simultaneously destroyed by the body. The body regulates the amount of dopamine from moment to moment by adjusting both the rate of production and the rate of breakdown.
This article originally appeared here in Josh’s blog. Republished with permission.