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Mdivi-1 Inhibition of Drp1 (CVB and Herpes inhibition)

mitoMAN

Senior Member
Messages
625
Location
Germany/Austria
Mdivi-1

Dr. Prusty has tested this Peptide to be highly effective in vitro but there have not been any studies conducted in human trials so far.
Contrary to SS-31, this is not only boosting Mitochondria but also inhibitng Drp1 and other Protein Kinase aspects needed for viral reproduction of Herpes and Coxsackie Virus.

Resources:
Inhibition of Drp1 attenuates mitochondrial damage and myocardial injury in Coxsackievirus B3 induced myocarditis
https://pubmed.ncbi.nlm.nih.gov/28131843/

Coxsackievirus B Escapes the Infected Cell in Ejected Mitophagosomes
https://jvi.asm.org/content/jvi/91/24/e01347-17.full.pdf

Indeed sudies indicate that SS-31 and Mdivi-1 do synergize pretty well.

Synergistic Protective Effects of Mitochondrial Division Inhibitor 1 and Mitochondria-Targeted Small Peptide SS31 in Alzheimer's Disease
https://pubmed.ncbi.nlm.nih.gov/29400667/


The substance has been well studied in Animals so far.
Dr. Prusty noted that long term usage might have toxic side effects however.

@dreamydays and @stefanosstef I think were interested in this Peptide.

So I decided to host a 3rd Party laboratory testing of a Mdivi-1 Supplier from Alibaba.
Anyone interested to join, please PM me or post here.


I will provide you with our Discord Server that is dedicated to analysie and custom synthesize research medications useful for ME/CFS.
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis. Li et al. J Neuroinflammation 2019
Background
Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.

Methods
We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined.

Results
Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry.

Conclusions
Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells.
 

mitoMAN

Senior Member
Messages
625
Location
Germany/Austria
Thanks I totally forgot about that study you posted. Very good you brought it up again - I had remembered Mdivi-1 mainly for its effect on mitochondria!

so far I am still waiting for more people to show interest in lab testing as I can't afford the costs purely myself.
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
Has Davis tested mdivi-1 with the nanoneedle? Why aren’t they doing more research with mdivi-1 or other small molecules to try prove/disprove if mitochondrial fragmentation truly do play a significant metabolic role in ME/CFS cells?
 

mitoMAN

Senior Member
Messages
625
Location
Germany/Austria
I don't know about Ron Davis but Dr.Prusty had good results invitro.
This drug is far away from human trials however from what I understand.

As the above study indicates Mdivi-1 could also be an important Modulator of T-cells. Similar to the effect of Ativan/Lorazepam in Ron Davis Seahorse Instrument? That would be fantastic of course. From what I understood lorazepam also temporarily increased ATP production in mitochondria and modulated the T-Cells to work effectively for a few hours.
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
I don't know about Ron Davis but Dr.Prusty had good results invitro.
This drug is far away from human trials however from what I understand.

I don’t know if mdivi-1 or anything similar targeting Drp-1 will ever be a studied as a potential human treatment, because mitochondrial fission also serves some very important housekeeping and other functions that mitochondria need to do on a frequent basis. You don’t want to fully inhibit it. Even Prusty said it’s dangerous to inhibit it for long. The ability of mitochondria to respond to energy needs and signals by altering their morphology and modulating fission/fusion balance are critical to cellular function.

What I’m interested in is proving or disproving that mitochondrial fragmentation is one of the main drivers of the metabolic problems seen in ME cells, and then figuring out what upstream dysfunctional signals (before Drp-1) are telling the mitochondria to remain fragmented and not increase fusion to meet energy needs.

I have a feeling even if you could fine tune mdivi-1 inhibition to not inhibit too much and still give some flexibility that by not targeting the upstream signaling causing all of this then the drug will eventually stop working or not work at all.