Cancer drug potential for reducing a-synuclien aggregates
 

A new protein capable of reducing the risk of Parkinson's disease identified | TheHealthSite.com


LAG3 inhibitor made by Norvartis is in Phase 1/2 clinical trial for solid tumor cancers.

Beyond PD-1[mdash]selected immuno-oncology drug therapies in development : Immuno-oncology moves beyond PD-1 : Nature Biotechnology : Nature Research

Another article on LAG3 and PD
 

The following article contains some more information regarding the recent paper on the (possible) link between the LAG3 protein and PD.

Experimental Cancer Therapies Could be Viable to Treat Parkinson’s

"Several clinical trials are testing antibodies blocking LAG3 as cancer immunotherapy. Ted Dawson said he has initiated discussions with potential sponsors about testing such antibodies in Parkinson’s patients. He envisions such a treatment could benefit patients ranging from pre-symptomatic, up to mid-stage disease."

“We are really excited and optimistic about the findings, . . . I think our findings can immediately move into patients, since there are really good LAG3 therapeutics already tested in cancer patients.”

Just to be clear, this is talking about stopping the SPREAD of malformed alpha-synuclein from one neuron to another. In other words, if this works, it would stop the progression of Parkinson's Disease - obviously a completely wonderful achievement.

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

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

2016 Nobel Prize Awarded for Autophagy Research
 

As a side note to the previous conversation, The 2016 Nobel Prize for Physiology and Medicine was awarded to Yoshinori Ohsumi for his groundbreaking discoveries underlying autophagy.

Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.

The 216 Nobel Prize in Physiology or Medicine - Press Release