Jonathan Sackner-Bernstein is transforming the treatment of Parkinson’s disease (PD). First, he discovered that the brain cells (dopaminergic neurons) in Parkinson’s patients are exposed to excess dopamine, reaching toxic levels. Next, he identified a drug that reverses disease pathology by reducing dopamine levels in 10 studies using laboratory models of PD
As an academic physician, Sackner-Bernstein leverages lessons learned at the US Food and Drug Administration (where he received 2 Commission’s Awards) and the US Defense Advanced Research Projects Agency (in a central role for the launch of the US Biological Technologies Office with its initial focus on neurotechnology).
Jonathan’s history of identifying contrarian views is remarkable for consistently being proven correct by subsequent studies and analyses. His optimism that PD will be conquered by reducing dopamine is supported by scientific data. And this drug therapy is poised to enter Phase 2 clinical trials, with data as soon as 6 months following trial launch.
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Michel0220
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I am so excited for this! The last interview you did with him was fascinating and I was just on his “right brain bio” website last night! Thank you for all of the informative interviews you do, Michel!
I urge great caution in accepting Sackner-Bernstein's unusual theory. Depicted here are a list of mutations affecting alpha-synuclein and that cause early onset Parkinson's. Note that the mouse engineered to have the A53T mutation develops Parkinson's motor impairments similar to humans.
"PD is strongly associated with the appearance of dopaminergic neuronal cytoplasmic inclusions called Lewy bodies. These are the leading pathogenic hallmarks in brain biopsies of PD patients, and are not present in healthy individuals. In 1997 Lewy body inclusions were shown to contain aggregates of αS [alpha-synuclein], a 140 amino acid protein which has consequently been implicated as the likely cause of familial PD. Further evidence is provided by the fact that duplication, triplication and autosomal dominant missense mutations in the SNCA gene lead to early onset forms of PD. It is now believed that the misfolding and subsequent aggregation of αS is a primary cause of dopaminergic degradation in PD."
mutations affecting alpha synuclein and that cause early onset Parkinson's.
Thanks but what causes the amino acids to alter? His work as I understand speaks to one functional driver of PD but the underlying mechanism is still unknown. My cursory examination, I’m new here, is that it’s autoimmune/auto inflammatory. Can you elaborate on this?
Genetic mutations exist across every disease. The question is what causes the mutations. I’m not referring to familial mutations of which make up a reporter 5% of PD cases. What is the mechanism by which the genes mutate?
Parkinson's that is not caused by familial genetic mutations is generally caused by toxic exposures. Permethrin, for example: healthunlocked.com/cure-par...
We know that in Parkinson's patients, adding dopamine leads to dyskinesis in some people. While it doesn't in non-PD people.
I've wondered if misfolding and damaging dopamine cells is the body's way to respond to something else, in order to preserve itself in part. Since the other thing that leads to dyskinesis, might have significance if dopamine wasn't being reduced.
Anyone had their own thoughts about this?
I'm interested to see his theory about reducing dopamine as a way out of PD. (Seems unlikely that completely reducing it would work or it wouldn't show up in the first place.)
Shortly after being diagnosed, when experimenting with levodopa medication there was an occasion when I took too much and experienced dyskinesia. I expect that would generally be the case, even for those without Parkinson's.
Research has shown that it's not the case. The dyskinesia shows up if you have Parkinson's and take too much or reach a point where you need a lot. But the same on non Parkinson doesn't produce dyskinesias.
Thanks for your reply. I was asking the previous commenter if he had links to the research showing dyskinesia cannot occur in non-Parkinson's individuals.
It's something I read within the last year but I'm not organized about PD research yet, so don't have it logged. I remember it was a resource I respected and talked about actual research. It's not specifically that they can not occur in non-PD, but that the rate of occurring was statistically significant that it occurred in PD patients with CLDL but not with non-PD patients.
I'm thinking probably the Davis Phinney Foundation.
This MJFF article has an idea of why it'd show in PD but it's not where I'd read more specific reference. michaeljfox.org/news/dyskin...
Googling, here's an NIH article about,
"With the dose of levodopa used in clinical practice, LID occur almost exclusively in patients with idiopathic Parkinson's disease, whereas normal people and those with other neurological diseases do not develop LID.6,7"
Will be very interesting to see where he stands today, as the last time I spoke to him he was still very busy convincing others of his theory and arranging finance for a double blind etc (and not getting much help from pharma by the way). If that is still the case (?) maybe we Parkinsonians should all step up and donate...
Well conventional thinking doesn’t seem to have got us anywhere for a long time, and certainly there has been no revolution in the 8 years since my diagnosis. I welcome a different approach and we need a few alternatives, not least to shake things up a bit. If you need a movie script then one man working alone against the might of pharmaceutical giants to come up with a solution, would be quite something. Let’s hope there is a happy ending!
I shared the gist of the video and the website ( rightbrainbio.com with my neurologist
Here is what he had to say:
“I am not familiar with this company, but I have some understanding of the idea behind their approach. There has been an argument about whether dopamine has toxicity to cells in Parkinson disease - among the neurotransmitters, it seems to be a more reactive chemical, and in the very active dopamine-producing cells, dopamine may be mediate some of the damage the cells endure in PD. The symptoms of PD are certainly due to a total loss of dopamine production, but this team argues that concentrations of dopamine within the remaining dopamine-producing cells are elevated and potentially damaging. There's still a lot of debate about this. People have studied whether levodopa is either protective or damaging, but it seems to be neither - and if it is not damaging, then this seems to counter the argument that dopamine is toxic to cells. But whether dopamine is harmful, helpful or neutral may be related to where in the cells the dopamine is concentrated and how it's being stored or utilized. It's really not clear at this point.
Ultimately, this is still an investigational approach. We'll need to see where the trials go to determine if it's a viable theory for countering PD. “
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