- α-synuclein, yes the very same neuronal protein thought to be the culprit behind PD, and that Ambroxol has been found to reduce (I prefer dispose of) by increasing GCase enzyme activity. So can we extrapolate that Ambroxol may be able to help people with Melanoma too? maybe we can, but the science is definitely not there yet to make that link:
Read on
"Several studies have shown that melanoma occurs two to six times more frequently in the Parkinson's population than the healthy population," says Dexter Dean, Ph.D., a postdoctoral fellow at the National Heart, Lung, and Blood Institute (NHLBI), who is presenting the work at the meeting. "What's more, the protein involved in Parkinson's disease, α-synuclein, is elevated in melanoma cells."
The idea that defective alpha synuclein causes melanoma makes sense given the vastly increased incidence of melanoma in Parkinson's patients. This study is a progress report on the investigators' efforts to find a mechanism for this. They are not done yet: "We hypothesize that α-syn, a pathogenic amyloid, infiltrates the process of functional amyloid formation of Pmel17, which alters melanogenesis, contributing to increased melanoma risk with loss of pigmentation. Future work will be dedicated to investigating this hypothesis."
Ambroxol has an excellent safety record, so I suppose no harm in trying for a person with melanoma.
Very old association via epi studies which are usually seriously flawed. (too many confounding variables that many don't consider or even think about). Ambroxol is a dated drug proposed as a "repurposed" drug. been there; done that.
Mullin's trial was somewhat of a farce. non random, no controls, n= 17 unblinded, supposedly oriented towards Glucocerebrosidase Gene Mutations (GBA1).
Mullins thinks that GBA1 mutations are the most important risk factor for Parkinson disease (PD). Really Stephen? don't think so.
Dexter Dean adds a brilliant observation of his own: " "What's more, the protein involved in Parkinson's disease, α-synuclein, is elevated in melanoma cells." So what. A-syn is elevated (OVER EXPRESSED) in many other types of cancerous tumor cells including the brain, breast, colorectal, and ovary. Any associations there Dean with PD?
For PD, a-syn (in its progressive cytotoxic form) is primarily relevant in terms of lewy body progression (spread from the brain stem to the frontal neocortex) because Lewy bodies are intra-neuronal cytoplasmic inclusions whose primary structural component is α-Synuclein.
"Future work will be dedicated to investigating this hypothesis."..says it all.
glad to hear the world is flat. by the way, go back and read the dose protocol used by Mullins.
"We performed a single-center open-label noncontrolled clinical trial of oral ambroxol therapy (escalating dose to 1.26 g per day (420 mg 3 times per day)".
"The 186-day exposure period comprised 28 days of dose escalation, with each dose administered 3 times per day as follows: 60 mg (days 1-7), 120 mg (days 8-14), 180 mg (days 15-21), and 300 mg (days 22-28). This exposure period was followed by 158 days of administration of ambroxol at 1.26 g per day (420 mg 3 times per day). Patients were issued ambroxol therapy in 2 batches, 1 at baseline and 1 at 93 days. All patients were taking dopaminergic therapy."
IOW, Mullins ended up using 42 tabs at 30 mgs.per tab per day for 158 days (85% of the study)
The problem is that Ambroxal hardly qualifies as a vitamin or mineral supplement that a person would take as a preventative measure. It more typically comes into the picture late in the game and usually to address other conditions.
In my case, an odd blemish appeared on my lower eyelid shortly before the pandemic hit. When it persisted for a few months I finally saw a doctor about it who suggested it was probably “blepharitis“ and recommended a hot compress. A more recent visit to an ophthalmologist (now just over a year since the problem first arose) revealed that the “blepharitis” - which currently spans across nearly 75% of my lower lid- may be something a bit more serious.
Fortunately, what was initially suspected to be a sebaceous carcinoma, turned out to be a somewhat less lethal basal cell carcinoma... yay. I’m currently awaiting an appointment date to get it excised. *Moral of the story: PWP need to pay attention to those odd bumps and blemishes.
gosh I just finished reading ,first scan, to see if I should eat ripe Banana's , my favourite, I remember seeing a bunch of the key words in the above discussion, so I will have to read and soak it in before it gets countered... here it is, it may fill in a hole or 2?
This is a replacement article the correct one was wrong
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Multiple mechanisms to clear a-synuclein with natural substances (in mice).
