Fight to Cure Lupus: A Proof of Concept in an Animal Model, 2019

The Jerusalem Post:
Ben-Gurion University develops miracle molecule for fighting Lupus
NIBN, BGU and NIH researchers make breakthrough in the 'Fight to Cure Lupus: A Proof of Concept in an Animal Model', reported in the prestige journal Science.
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“Our breakthrough is identifying a new pathway for the exit of mitochondrial DNA that we can either trigger under controlled conditions or inhibit using our novel molecule that we specifically developed to prevent the formation of this pathway,” said Shoshan-Barmatz in a statement. “Since the results thus far with lupus have been so promising, we believe that the molecule will be beneficial with regards to other diseases such as Alzheimer’s, Crohn’s and ulcerative colitis – as our preliminary results already support."
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I find media reports like this a bit frustrating because they don't say much useful, except unjustified hype about the impact.

Even the abstract of the article is much more readable.
Mitochondrial DNA (mtDNA) is normally kept within the mitochondria. It can be released into the cytosol in response to stress and thus encounter cytosolic DNA sensors, triggering type I interferon responses. During apoptosis, mtDNA release is mediated by macropores in the mitochondrial outer membrane (MOM) created by oligomerization of the proteins BAX and BAK. Kim et al. found that during oxidative stress, mtDNA escapes instead through macropores formed by oligomerization of voltage-dependent anion channels (VDACs) (see the Perspective by Crow). In a mouse model of lupus, an inhibitor of VDAC oligomerization diminished mtDNA release and downstream signaling events. This treatment reduced lupus-like symptoms in the model, suggesting a potential therapeutic route for conditions mediated by mtDNA release.
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https://science.sciencemag.org/content/366/6472/1531

This is highly unlikely to be a major treatment for Lupus, yet the research is quite interesting.

Wikipedia said:
VDAC1 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms.[24] Of the three isoforms, VDAC1 is the main calcium ion transport channel and the most abundantly transcribed.[12][25] VDAC1 is involved in cell metabolism by transporting ATP and other small metabolites across the outer mitochondrial membrane (OMM) allowing regulation of the TCA cycle and, by extension, reactive oxygen species (ROS) production.
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https://en.wikipedia.org/wiki/VDAC1
https://en.wikipedia.org/wiki/Voltage-dependent_anion_channel
 
Isn't doing this analogous to blocking the pain, and the perception of, a severe leg injury in order to reduce the symptoms associated with such an injury.

How do they know that removing the organisms 'awareness' of a potentially serious and ongoing problem, and thus removing what the organism has evolved as an appropriate response to it, won't turn a 'debilitating' chronic condition into a short term but fatal one?

I mean presumably the response, and the signals, exist for a reason.

Sticking a piece of tape over a engine warning light may seem like a good way to sort out an irritating light, but doing so rarely ends well unless action is taken to, you know, diagnose and fix the problem that caused the light to come on in the first place.

Especially when other warning signs are evident, like not being able to drive uphill, or above 30mph.

The whole of modern medicine seems to be about finding new bits of tape to cover up warning lights, rather than fixing the problems that caused the light to come on in the first place.

'Understandable' if your only priority is to get from A to B now, but not a solution, or shouldn't be, if you give a damn about peoples quality of life, or even their health.
 
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Wonko said:
Isn't doing this analogous to blocking the pain, and the perception of, a severe leg injury in order to reduce the symptoms associated with such an injury.

How do they know that removing the organisms 'awareness' of a potentially serious and ongoing problem, and thus removing what the organism has evolved as an appropriate response to it, won't turn a 'debilitating' chronic condition into a short term but fatal one?

I mean presumably the response, and the signals, exist for a reason.

Sticking a piece of tape over a engine warning light may seem like a good way to sort out an irritating light, but doing so rarely ends well unless action is taken to, you know, diagnose and fix the problem that caused the light to come on in the first place.

Especially when other warning signs are evident, like not being able to drive uphill, or above 30mph.

The whole of modern medicine seems to be about finding new bits of tape to cover up warning lights, rather than fixing the problems that caused the light to come on in the first place.

'Understandable' if your only priority is to get from A to B now, but not a solution, or shouldn't be, if you give a damn about peoples quality of life, or even their health.
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not every signal exists for a reason, or for a good reason actually, complex systems fail, all the time, everywhere, if not, you would not get sick first place.
 
butter. said:
not every signal exists for a reason,
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How can you possibly know that?
butter. said:
or for a good reason actually,
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Debatable, philosophical.

I would think that most, but not necessarily all, 'random' signalling would be eliminated by evolutionary processes within a few hundred million years or so.

butter. said:
systems fail, all the time, everywhere,
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Systems wear out, and/or become unsuited to their environment if it changes, this is not the same thing as the system failing.

On the contrary, this is the system behaving as it should, from an evolutionary standpoint.

butter. said:
if not, you would not get sick first place.
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Maybe in the 12th century this would have been an appropriate viewpoint.
 
Apologies in advance for my lack of knowledge. Is Lupus a bit like ME i.e. no biomarker* and no treatments - is it part of the spectrum ME, post-treatment Lyme diseases, post---name your pathogen--.

I think I recall that Ron Davis highlighted concerns about using animal models to study diseases -- they may be misleading (from SEPSIS research Ron was involved in?).


*I used to write "diagnostic test" but @Jonathan Edwards et al impressed on me the emphasis should be on biomarkers rather than diagnostic tests --- progress!
 
FMMM1 said:
Apologies in advance for my lack of knowledge. Is Lupus a bit like ME i.e. no biomarker* and no treatments - is it part of the spectrum ME, post-treatment Lyme diseases, post---name your pathogen--.
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Not like ME at all. There is well established pathology. There are pretty reliable blood tests. And there are very effective treatments for a lot of the problems although not all. We understand the mechanism reasonably well. There are animal models that reflect some of the steps in the chain but none that model the causation in humans very closely. But that does not matter because we have been able to work out much of what is going on from clinical studies in humans.
 
Jonathan Edwards said:
Not like ME at all. There is well established pathology. There are pretty reliable blood tests. And there are very effective treatments for a lot of the problems although not all. We understand the mechanism reasonably well. There are animal models that reflect some of the steps in the chain but none that model the causation in humans very closely. But that does not matter because we have been able to work out much of what is going on from clinical studies in humans.
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Is it a autoimmune disease i.e. caused by autoimmune antibodies?
 
FMMM1 said:
Is it a autoimmune disease i.e. caused by autoimmune antibodies?
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Yes. Whereas most autoimmune diseases work through one or two linked antibodies lupus has a whole family of autoantibodies. The central ones are antibodies to nuclear proteins and DNA - antinuclear antibodies. The secondary ones include antibodies to platelets, to phospholipid, to lymphocytes, and others.
 
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