Neuroprotection from the perspective of a Parkinson patient


#1

Introduction
I was diagnosed for Parkinson (PD) in August/September 2014. The doctors were generous in helping me with medication against symptoms (L-Dopa). After a while, I wanted to be better informed about the prospects. An interesting source of information was provided by the book of William J. Weiner and others, entitled “Parkinson’s Disease: A complete guide for patients and families” (Baltimore, MD: Johns Hopkins University Press, 3rd Edition, 2013). Among the possible medications, Selegiline was singled out because of its potentially disease-modifying effects. When asked, my neurologist advised Rasagline (Azilect) as even better medication with similar working (but differently in terms of the mechanism). Since I take Azilect, I have milder symptoms. Unfortunately, Azilect is not covered by the insurance in the Netherlands and it is expensive. The disease-modifying effects are sometimes questioned.

This experience with Azilect stimulated me to orient myself further on other drugs that may influence the progression of the disease. In this communication, I report about my findings.

Medication against PD
It is important to distinguish three types of medications and therapies:
1. Medication against symptoms (e.g., L-Dopa);
2. Neuroprotection influencing the progression of the disease;
3. Therapy aiming at curing the disease.

The first category is well taken care off in the Netherlands. Doctors, hospitals, and para-medical professions collaborate in the so-called ParkinsonNet. Therapies for curing the disease are not yet available. One expects further developments in gene-therapy and perhaps stem-cell therapy, but the time frame is too long for the current generation. In the case of gene-therapy, one would bring a virus into the brain that would induce the production of the enzymes needed for producing dopamine. Stem-cell therapy seems most elaborated in the Dr. Wu-center in Beijing; I plan to pay there a visit, and will report later on that.

Several companies are working on a vaccine against alpha-synuclein, a protein stapling in the brain cells affected with PD and leading in the longer term to Lewis bodies and also dementia. Affiris in Vienna is championing with a clinical trial; but this trial is in this stage only accessible for citizens of German-speaking countries. One expects a disease-modifying effect from the vaccine.

Neuro-protectiva
Let us focus on the second category of neuroprotective substances. As noted, Azilect (and Selegiline) claim a disease-modify effect, but also other substances have been mentioned and are studied in this context. Most research is still pre-clinical. There are clinical trials, but the results are often ambiguous.

Israpidine
One of the substances that is currently under investigation for neuroprotective effects in a clinical trial is israpidine. Israpidine is one of a family of so-called calcium-channel blockers which are commonly used against high blood pressure. I used, for example, amlodipine on prescription. Different from amlodipine, however, isradipine passes the brain-blood-barrier and therefore may have an effect in the brain. Among the various substances with these properties, research is focusing on isradipine; for example, in a clinical trial at the San Diego School of Medicine (UCSD; at http://health.ucsd.edu/news/releases/Pages/2014-09-30-phase-III-parkinsons-clinical-trial.aspx).

It is a minor effort to change one’s medication into isradipine if one use other medication against high blood pressure. My doctor agreed although she warned against high hopes. She noted that isradipine may be less effective than amlodipine, but I use a cocktail of medicines, and it is possible to replace this component. For PD patients, it seems something to consider. See also, for example, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917467/

Hop
Recently (April 11), the Dutch Parkinson Association reported that hop may be neuroprotective. Again, the research is still in early stages and results are based on animal testing. Hop is an ingredient of beer, but one would have to drink a lot of beer in order to expect some effect. Some beers contain more hop than others. However, hop can easily be bought at a shop or the internet, and it is not expensive. I bought a package and it says on the box that one should not take more than three pills a day, each containing 65 mg of hop. According to the manufacturer, hop solves a whole series of health problems.

Nicotine
It is known since decades from epidemiological investigations that smokers have significantly less chance of developing PD. Even in the case of twins, the patient affected may have a brother or sister who smokes and has therefore significantly less chance of getting the disease. There is mounting evidence that nicotine has neuroprotective effects (e.g., at http://www.ncbi.nlm.nih.gov/pubmed/22693036; this paper provides an overview of clinical trials with neuroprotective substances in an Annex). The lack of research in this area is sometimes attributed to the fact that nicotine as a natural substance cannot be patented.

A large trial of nicotine pads is currently undertaken by American and German researchers (at https://foxtrialfinder.michaeljfox.org/trial/2968/ . (Unfortunately, I could not participate because of my previous disease history.) The results are expected in the summer of 2017. For me, it is not attractive to wait for these results because neuroprotection may work best in the early stages of the disease.

While one cannot advise at the level of society to experiment with nicotine, the risk assessment is, in my opinion, different for individual patients. In the trial one varies the dose between 7 and 28 mg/day. The lowest dose for pads in the drugstore is 7 mg/pad. One can also use chewing gum with nicotine in low doses.

A disadvantage of nicotine in my case is its effect on blood pressure and harming the vessels. On the other side, nicotine is a stimulant and I think that I feel much better since I use these pads. One expects nicotine to have effect mainly on the non-motoric aspects of PD, among which cognitive impairments. Nicotine is also a possible candidate as medication for other neuro-pathologies such as Alzheimer, ADHD, etc.

Ubiquinol
Ubiquinol (the reduced form of ubiquinone) is a food supplement that stimulates the energy household in the cell and has anti-oxidative properties. It may have all kinds of positive health effects and is probably harmless to take. A clinical trial did not lead to evidence and was stopped; but some (e.g., German) doctors still advise to use it. A disadvantage is that one may have to take large amounts (> 600 mg) for some effects and the supplement is expensive in its reduced form. Ubiquinol is a natural substance and otherwise metabolized.

Conclusion
As a patient, one has a time horizon different from the authorities for food and drugs administration who have to test new substances for their safety and effectivity. If one of these substances indeed would be neuroprotective, however, it may be important to begin using them as soon as possible. The risk assessment is an individual affair, but one is well advised to consult one’s GP because of possible side-effects. Using nicotine notably can be harmful. Let me emphasize that I am not a doctor, but a patient who is orienting oneself. I most welcome comments since I may have overlooked important considerations.


Loet Leydesdorff
Amsterdam, April 18, 2015.


#2

Hello Loet

Thank you very much for such a detailed and considered article. I agree with you about the standards against which one should measure such substances being diffrent for patients than for authorities and researchers.

I take Rasagiline - and (well, certainly for the moment) that is free on the NHS. It is, of course, impossible for me to tell if it's slowed progression (because you can't do RCTs on yourself!) and that's possibly the main problem with self-administered research.

Does Research have anything to add, please?

And do keep posting, Loet.

With very best wishes

Semele


#3

Someone warned me that taking such high doses of Ubiquinol may have severe side effects. Unfortunately, the system does not allow me to edit the original posting. Please, consider this paragraph as "to be deleted".

Best,

Loet

 


#4

Loet,

Thanks for such a long and well-thought-out piece. It is interesting to see prescribing differences between countries. I agree that PwP have a different attitude to risk.

I think there is some evidence, although not conclusive, that exercise slows progression slightly.

Semele,

You raise the issue of self-testing. I believe it can be done usefully - especially since the results are yours alone, and not diluted down with the results of other people with different genetics, different environments and, possibly, different underlying diseases.

John