Cure of the Week

C

You know I like a bit of a laugh but even I would not make this stuff up. It’s not even the first of April

I wonder if this will be the EAE (Cure of the Week) paper of the year. What a way to start the year:-)

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota. Lu XY, Han B, Deng X, Deng SY, Zhang YY, Shen PX, Hui T, Chen RH, Li X, Zhang Y

A magic bit of botany and it works via the microbiota. What more could you ask for? MS sorted……..

I wonder if this is how another “cure of the week” will work….

In this other study they go on a fishing trip to see what is the difference between MS and Health and catch a T cell. Not surprising as they essentially only look in the T cell compartment. They pull out a gene from MS and it is involved in Nedylation….Don’t know what it is? No I didn’t either… but after doing some reading it is going to take too much time to explain and if I did it would be called Zedylation as the Zzzzzzzzzzzs will arrive from your sleeping bodies.

If you go fishing that looks for stuff to go up and down,you have to be cautious that stuff goes up because a cell type expressing a gene goes up. But a *cancer (drug) was found to block the nedylation gene product and make cells commit sucicide and it inhibited EAE (abit)….. So is this coming to you in about 15 years time? We will have to wait.

For this reason I don’t do EAE “cure of the Week”

Ask yourself this….Do the EAE experiments completely inhibit disease as this what it is easy to do and something that only ameliorates disease abit is not good enough in such an optimised system. Half a relapse is still a relapse.

Next ask yourself how widely is the target expressed e.g. at www. biogps.org and if it is every where you are going to have lots of side effect issues.

Do some homework, look at the figures and see if they pass the smack you in the eye test…because if it doesn’t, the line your pockets with gold test for drug development is not going to work:-(.

Cell type-specific transcriptomics identifies neddylation as a novel therapeutic target in multiple sclerosis.Kim K, Pröbstel AK, Baumann R, Dyckow J, Landefeld J, Kogl E, Madireddy L, Loudermilk R, Eggers EL, Singh S, Caillier SJ, Hauser SL, Cree BAC; UCSF MS-EPIC Team, Schirmer L, Wilson MR, Baranzini SE.Brain. 2020 :awaa421. doi: 10.1093/brain/awaa421

Multiple sclerosis is an autoimmune disease of the CNS in which both genetic and environmental factors are involved. Genome-wide association studies revealed more than 200 risk loci, most of which harbour genes primarily expressed in immune cells. However, whether genetic differences are translated into cell-specific gene expression profiles and to what extent these are altered in patients with multiple sclerosis are still open questions in the field. To assess cell type-specific gene expression in a large cohort of patients with multiple sclerosis, we sequenced the whole transcriptome of fluorescence-activated cell sorted T cells (CD4+ and CD8+) and CD14+ monocytes from treatment-naive patients with multiple sclerosis (n = 106) and healthy subjects (n = 22). We identified 479 differentially expressed genes in CD4+ T cells, 435 in monocytes, and 54 in CD8+ T cells. Importantly, in CD4+ T cells, we discovered upregulated transcripts from the NAE1 gene, a critical subunit of the NEDD8 activating enzyme, which activates the neddylation pathway, a post-translational modification analogous to ubiquitination. Finally, we demonstrated that inhibition of NEDD8 activating enzyme using the specific inhibitor pevonedistat (MLN4924) significantly ameliorated disease severity in murine experimental autoimmune encephalomyelitis. Our findings provide novel insights into multiple sclerosis-associated gene regulation unravelling neddylation as a crucial pathway in multiple sclerosis pathogenesis with implications for the development of tailored disease-modifying agents.

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MouseDoctor

6 comments

  • Pomegranates are delicious, but they are messy ******** to eat. Last time I tried to prepare one, I got juice all up the wall. I don’t know about nedylation, but they certainly stain.

  • MD – it’s been a miserable start to the year. There’s no doubt a lot of worry, uncertainty in the MS community about vaccines, treatment, delayed diagnosis. Any chance of a post about the 5 most exciting ‘prospects’ in MS research in 2021. Cheer us all up a bit? Please 🙏

    • New Years Honors list in a crystal ball is ProfGs domain, He is glass half full and has an eye in the Pharma ball, which is where the real answers lie. It is a thank less task.

      We can know what out own exciting stuff is and getting ChariotMS started and recruting will be a big move forward…The imods will apear this year and the Brutons tyrosine kinase will be a new battle ground.

      However what is the emoji a nose as it sure looks like meat and two veg.

  • If only I was a mouse than i wouldn’t even need a doctor. I could heal myself by eating… or not eating at all. Well 2 bad I just went to the supermarket. Perhaps Terry Wahls will sent me a discount for a supplement containing the extract. Aldo I might give the peel a go it can not be much harder to chew on than the seeds.

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