A Computational Model of Levodopa-Induced Toxicity in Substantia Nigra Pars Compacta in Parkinson's Disease

[pvw2]

Can the technical people explain the significance of this article:

biorxiv.org/content/10.1101...

[qazwsx11]

The researchers produced a computational model that can be run on a computer and which will help in understanding the mechanism behind neurodegeneration and provide insights for developing disease-modifying therapeutics.

It is believed that the the cause of Parkinson’s is energy deficiency caused by oxidative stress aka inflammation, which kills dopamine generating neurons. However taking levodopa in large quantities leads also to increase of inflammation which in turn kills more of the remaining dopamine generating neurons. This process can be countered by supplemental antioxidants such as glutathione.

The model provides researchers to simulate different parameters and improve treatments.

I don’t find anything that’s not already known in this article other than this is a computer model.

[sharoncrayn in reply to qazwsx11]

"I don’t find anything that’s not already known in this article"

I don't agree with your conclusion since most neurologists that I have worked with believe the standard prescription l-dopa drugs are the only "primary" avenue in treating PD.

In contrast..."We hypothesize that energy deficiency can lead to LDOPA-induced toxicity (LIT) in two ways: by promoting dopamine-induced oxidative stress and by exacerbating excitotoxicity in SNc. " which would imply l-dopa is not all that beneficial.

sharon

[qazwsx11 in reply to sharoncrayn]

My neurologists warned my about the toxicity in high dozes. Perhaps the excitotoxicity in SNc is new finding. In theory l-dopa may not be beneficial but I can have a life. Would love to hear about better treatments.

[sharoncrayn in reply to qazwsx11]

I was merely commenting about it being "common" knowledge. Perhaps it is for some physicians, but no other drug/treatment is so readily available that can work initially like l-dopa so most physicians continually prescribe it whether they are aware of its long term toxicity or not.

Sharon

[pvw2 in reply to sharoncrayn]

In the very early stages of PD, my neurologist has prescribed Rasagiline and Pramipexole for me, but he anticipates eventually needing to prescribe L/C as PD progresses. In more advanced PD Rasagiline and Pramipexole are used in conjunction with L/C. But, as you say there is no substitute for L/C. The natural means of fava beans or velvet beans are still L/C with dosage difficult to determine.

[sharoncrayn in reply to pvw2]

Remember, sinemet and rytary are combining the pharmaceutical compounds of l-dopa and carbidopa. MP doesn't. MPuriens is simply l-dopa plus other ingredients from MP depending on the extract. Big difference.

Sharon

[pvw2 in reply to sharoncrayn]

So only fava beans have both. My understanding is without carbidopa, not only is dosage of l-dopa in MPuriens (velvet beans) unknown; the lack of absorption depends of other food eaten.

[sharoncrayn in reply to pvw2]

No, Fava beans do not contain levels of carbidopa that I am aware of.

Fava beans contain approximately 0.5% L-DOPA, much less when dried (anecdotally dried fava has little effect)/

MP = about 4-6% L-DOPA

Mucuuna does not contain a DOPA decarboxylase inhibitor (DDCI) like sinemet. Therefore bioavailability in the CNS is presumably less. (The latter comment has been contradicted in the literature, JON, showing just the opposite).

Sharon

[pvw2 in reply to sharoncrayn]

Is this article not valid, quote:

Conclusion: The results of this study indicate that faba beans are a good source of natural L-dopa and C-dopa. The quantification of this capacity according to the stage and the plant part could be suitable for applications in the food industry and in plant medicine. The consumption of fava beans can increase the levels of L-dopa and C-dopa in the blood, with a marked improvement in the motor performance of the patients with parkinson disease, without any side effects.

ncbi.nlm.nih.gov/pmc/articl...

However, overdosing on fava beans is not uncommon. "without any side effects" is questionable.

[sharoncrayn in reply to pvw2]

Good catch I must admit. They suggest in fava the ratio is 2:1 for C-dopa vs. L-dopa. Interesting. I would have to go back through their references to see if this finding is duplicated. Right now, I don't know.

In contrast in sinemet 10:100 for example, the ratio is 1:10 for C-dopa vs. L-dopa. Quite a difference versus their findings for fava.

The big question: is C-dopa found in fava similar to or identical to carbidopa found in sinemet? In sinemet, carbidopa "Anhydrous" is the anhydrous, levorotatory isomer of a synthetic hydrazine derivative of the neurotransmitter dopamine.

Also, is carbidopa really that important in treating PD? Some physicians think it is toxic as well, if not more so than l-dopa long term.

Sharon