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Originally Posted by dan1000
BUT
Here's the thing: Most of us have had PD for years, even if we have been diagnosed with it only recently. The question is: Do most of our dopaminergic cells already have some level of malformed alpha-synuclein within them? Not enough to have killed all the neurons yet, but some? If so, the approach taken by this drug won't work, because once the malformed alpha-synuclein is inside a cell, nothing the drug does will help that cell. The drug only helps cells that have not yet been entered by malformed alpha-synuclein.
SO
Open question (I'm a computer scientist, not a biologist): For those of us diagnosed with PD, do most of our dopaminergic cells already have some level of alpha-synuclein within them, even if they are not yet dead?
Final thought: It seems to me that what is needed is a drug to clear out the malformed alpha-synuclein from within cells. That way, not only would the progression of the disease be stopped, but cells that are currently burdened by malformed alpha-synuclein but that have not yet died, would become productive again. So there could be some reversal of the disease, not merely a stopping of its progression.
Dan
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Dan, your observation is correct. However, researchers on PD treatments are currently tackling PD from multiple directions. This includes halting or slowing progression, as would be the case with LAG3 research. It also includes multiple studies on autophagy (the cleansing and rebalancing of our cells), which is what you would be hoping for to not only slow, but to halt and reverse the disease progression. As you suggested, those of us with PD do still have functioning dopamine neurons that have been "infected" with aggregation of mutated a-syn. So, in theory, by removing that protein there could be some reversal in symptoms.
One of the hot topics on this board recently has been the Nilotinib research. This is exactly what the drug would work on with neurological diseases, in theory. Nilotinib is a tyrosine kinase inhibitor which penetrates the blood brain barrier and destroys toxic proteins by turning on the autophagy process inside neurons. There has also been discussion on some of the vaccine research in PD (e.g. AffiRis and Prothena). They use an immunotherapy approach to removing mutated a-syn. Finally, even the theory behind the Isradipine research would be relevant to this process. Isradipine slows the over-heated calcium channels of a-syn infected neurons mitochondria to get their source of energy from other channels. This, in theory, allows the body's natural immune system to help the neurons remove the mutated a-syn.
So, there are many approaches trying to do what you suggest. That being said, I doubt there are many of us with PD who would be unhappy if a therapy, like that involved with the LAG3 research, were to be developed. Slowing or halting progression for early and mid-stage PD would be a huge development for many of us as well as for generations to come. I would be thrilled to see success with any of these approaches.
Gary