A. Parkinson treatments: do’s and don'ts
What are the best science-based treatment regimens for Parkinson’s disease? Not just to treat symptoms, but ideally also to slow down the disease?
How people with Parkinson’s are treated often depends on their neurologist. Still all too often, people do not get the best treatment regimen for their specific situation.
This is not to say that the treatment regimen described below is the only one and the best one. We summarised some main principles that could be useful and helpful for people with Parkinson’s to know.
Main Principles
- Try to use as little as levodopa for as long as possible (‘levodopa-sparing therapy’)
- If the patient is “young”, associate dopamine agonist; if old, better not
- Start or combine with drugs that are neuroprotective (e.g. MAO-inhibitors)
- When young or at early stage, start with levodopa-sparing drugs (e.g. selegiline, dopamine agonists, amantadine, or anticholinergics (Artane) for tremors)
- Take B vitamins (and the right forms of B vitamins) given that levodopa depletes B vitamin levels and increases homocysteine.
Levodopa Impairs the Energy Metabolism of the Basal Ganglia In Vivo
B. Drugs to slow progression of Parkinson’s
Most drugs for Parkinson’s disease mainly treat symptoms of the disease, and do not really slow down the progression of the disease.
Take for example levodopa. This drug is converted into dopamine, which is a substance that is substantially reduced in Parkinson patients. Levodopa however does not slow down the progression of the disease; it just improves symptoms for a while. But the disease still further progresses, which also leads to increased amounts of levodopa to be given to patients.
Another example are dopamine agonists, like pramipexole (Mirepex), ropinirole (Requip) or rotigotine (Kynmobi). These drugs stimulate dopamine receptors, but they do not address the root causes of Parkinson’s disease, like mitochondrial dysfunction, protein accumulation and oxidative stress.
However, some drugs could act more on such root causes, potentially slowing down the progress of the disease, instead of just suppressing symptoms.
Below you find an overview of such drugs.
1. MAO-B inhibitors like selegiline and rasagiline
Selegiline and rasagiline are monoamine oxidase B (MAO-B) inhibitors. This means they suppress the activity of the MAO-B protein (an enzyme).
MAO-B is an enzyme that breaks down dopamine in neurons. MAO-B inhibitors inhibit this enzyme, so less dopamine is broken down, which increases dopamine levels in the brain (in Parkinson’s disease, there is a shortage of dopamine).
Besides just increasing dopamine levels, MAO-B inhibitors like selegiline and rasagiline also seem to have neuroprotective effects (R) by virtue of:
- Antioxidant function
- Anti-apoptosis (preventing cell death)
- Increasing production of protective enzymes, bcl-2 proteins, neurotrophic factors
- Promoting mitochondrial function
- Direct impact on the shape of alpha-synuclein
Firstly, MAO-B inhibitors can reduce oxidative damage due to their specific pharmacological mechanism of action: inhibiting MAO-B enzymes.
MAO-B enzymes break down dopamine, and this process produces lots of free radicals. These are small, reactive particles that damage cell structures.
By inhibiting MAO-B, less free radicals are produced, leading to less oxidative stress, especially in dopamine-producing cells; the cells that get damaged with Parkinson’s disease.
The TEMPO trial showed that rasagiline slowed down the progression of Parkinson’s disease (in early-disease patients who didn’t take dopaminergic therapy yet) (R):
The ADAGIO study found that rasagiline delayed the need for antiparkinsonian drugs and slowed the progression of the disease (R).
The PRESTO study found a benefit from associating rasagiline in levodopa-treated patients (R).
Studies show that selegiline (Deprenyl) can slow down the progress of Parkinson’s disease (while vitamin E supplements didn’t have an effect) (R).
C. "Off-label” drugs for Parkinson’s
These are drugs used to treat other diseases than Parkinson’s which have been shown to reduce the risk or progression of Parkinson’s disease.
1. Terazosin
This drug is used in male patients to reduce symptoms of prostate enlargement (prostate hypertrophy). It’s an alpha-1-adrenergic receptor antagonist, meaning it blocks alpha-1-adrenergic receptors on cells.
When these receptors are stimulated, for example on blood vessel cells or cells lining the ducts that transport urine, these vessels contract.
By inhibiting alpha-1-adrenergic receptors, however, these vessels relax, which explains how terazosin could improve prostate hypertrophy or overgrowth, which presses on blood vessels and urine flow vessels.
However, this drug also has been shown to be associated with less Parkinson’s disease (R,R). Various studies show that people who take this drug have less risk of Parkinson’s disease (R,R). #
2. Rapamycin
This drug is used to prevent immune rejection of kidney transplants.
Rapamycin also has been shown to extend lifespan in dozens of animal studies. Therefore, in lower doses it is taken by many longevity enthusiasts to extend lifespan and healthspan.
Studies also show that rapamycin could be protective for Parkinson’s disease (R,R). Currently, clinical trials are ongoing using rapamycin-like drugs (“rapalogues”) to treat Parkinson’s disease (R).
Rapamycin could improve Parkinson’s disease via several mechanisms.
Firstly, it induces autophagy. Etc etc
Mitophagy etc
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