Welcome to #TenTweetNephJC
✳️10 tweets #NephJC catch-up ✳️
Perplexed by how gene dosage plays a role in ADPKD? Fascinated by futuristic stories of miRNA,CRISPR & want to see an application closer to daily life?
Read on!Here’s some good news for the ADPKD patient in your clinic.
✳️10 tweets #NephJC catch-up ✳️
Perplexed by how gene dosage plays a role in ADPKD? Fascinated by futuristic stories of miRNA,CRISPR & want to see an application closer to daily life?
Read on!Here’s some good news for the ADPKD patient in your clinic.
2/10
What did I miss?
ADPKD is caused by heterozygous loss of function(+/-) of PKD1/2.By virtue of autosomal dominant inheritance,1 copy of gene is normal(+).
This elegant study shows that harnessing function of(+)gene may hold the key to disease control in ADPKD.
PMID:35965273
What did I miss?
ADPKD is caused by heterozygous loss of function(+/-) of PKD1/2.By virtue of autosomal dominant inheritance,1 copy of gene is normal(+).
This elegant study shows that harnessing function of(+)gene may hold the key to disease control in ADPKD.
PMID:35965273
3/10
1 tweet methods
🐀
Mice progeny having one Pkd1/2 allele with reduced function(RC) was developed
Suppressor✂️miRNA binding element(MBE)✂️deleted(Δ17) by CRISPR
Study timelines⏳
✅Cyst prevention study(D18)
✅Disease stabilisation study(D26)
✅Longterm cyst Rx study(18 wks)
1 tweet methods
🐀
Mice progeny having one Pkd1/2 allele with reduced function(RC) was developed
Suppressor✂️miRNA binding element(MBE)✂️deleted(Δ17) by CRISPR
Study timelines⏳
✅Cyst prevention study(D18)
✅Disease stabilisation study(D26)
✅Longterm cyst Rx study(18 wks)
4/10
1 tweet results
Polycystin protein levels can be repleted in mice & human cell lines with PKD mutations by-
🧬Deleting the Pkd1-miR-17 binding motif (MBE) or
🚫Blocking miR-17 function (here using RGLS4326) PMID:31515477
PKD2∆17 (MBE deletion) also reduces cystogenesis.
1 tweet results
Polycystin protein levels can be repleted in mice & human cell lines with PKD mutations by-
🧬Deleting the Pkd1-miR-17 binding motif (MBE) or
🚫Blocking miR-17 function (here using RGLS4326) PMID:31515477
PKD2∆17 (MBE deletion) also reduces cystogenesis.
5/10
A figure paints 1000 words
Each founder progeny reiterated the results. Mice with deletions of MBE showed reduced cystogenesis, secondary to non-binding of repressor miRNA17 to Pkd1.
Mice with RC/- genotype(most susceptible) subjected to MBE deletion also had ⬇️ of cysts.
A figure paints 1000 words
Each founder progeny reiterated the results. Mice with deletions of MBE showed reduced cystogenesis, secondary to non-binding of repressor miRNA17 to Pkd1.
Mice with RC/- genotype(most susceptible) subjected to MBE deletion also had ⬇️ of cysts.
6/10
Give me something clever to say
#precisionmedicine
Future beckons.Ways to achieve this?
1. Changing guidelines to incorporate routine genetic testing
2. Ability to treat ADPKD from pre-clinical stage through disease progression
3. Possibly tackle extra-renal manifestations
Give me something clever to say
#precisionmedicine
Future beckons.Ways to achieve this?
1. Changing guidelines to incorporate routine genetic testing
2. Ability to treat ADPKD from pre-clinical stage through disease progression
3. Possibly tackle extra-renal manifestations
7/10
Chat consensus?
This,from the formidable @HumphreysLab #benchtobedside
"We are fortunate now in Neph that pharma & biotech are investing in drug discovery - we all benefit from increased academic-industry interactions."
We agree.Exciting time to be a nephrologist indeed.
Chat consensus?
This,from the formidable @HumphreysLab #benchtobedside
"We are fortunate now in Neph that pharma & biotech are investing in drug discovery - we all benefit from increased academic-industry interactions."
We agree.Exciting time to be a nephrologist indeed.
8/10
Quote of the fortnight
Could’ve picked many, but @jamiekwilliows frowned upon dazzling more jargon! Assimilating the complex science has been tough enough.
So here's something that implores us to keep calm & keep NephJCing!
Alright, Alright, Alright!
Quote of the fortnight
Could’ve picked many, but @jamiekwilliows frowned upon dazzling more jargon! Assimilating the complex science has been tough enough.
So here's something that implores us to keep calm & keep NephJCing!
Alright, Alright, Alright!
9/10
I want more info
✅ Follow the authors: @Vishal_D_Patel @RonakLakhia1 @HariniRamaling1
Tweetorial:
PMID: 32690722 by @mattlanktree
✅ Summary: @dakidneydoc
nephjc.com
✅ VAs: @sandyrvsdav @bhavya_dasara
I want more info
✅ Follow the authors: @Vishal_D_Patel @RonakLakhia1 @HariniRamaling1
Tweetorial:
PMID: 32690722 by @mattlanktree
✅ Summary: @dakidneydoc
nephjc.com
✅ VAs: @sandyrvsdav @bhavya_dasara
10/10
Final thoughts
A vision of promise from @Vishal_D_Patel
The field is realising that PKD1/2 drugs are feasible. That's a big START.
Options:
PKD1/2 mRNA-based therapy
PKD1/2 base-editing
Other cis-inhibitory motifs in PKD1/2
PKD1 mRNA-poorly spliced(another way to⬇️PKD1)
Final thoughts
A vision of promise from @Vishal_D_Patel
The field is realising that PKD1/2 drugs are feasible. That's a big START.
Options:
PKD1/2 mRNA-based therapy
PKD1/2 base-editing
Other cis-inhibitory motifs in PKD1/2
PKD1 mRNA-poorly spliced(another way to⬇️PKD1)
➡️Wishing everyone attending @ASNKidney KidneyWeek'22 a fabulous time!
#NephJC is going to be busy at #kidneywk. Join us there!🎉nephjc.com
Also, many exciting new trials are lined up to be unveiled, so stay tuned for the next NephJC!
Tweetorial by @SayaliBThakare
#NephJC is going to be busy at #kidneywk. Join us there!🎉nephjc.com
Also, many exciting new trials are lined up to be unveiled, so stay tuned for the next NephJC!
Tweetorial by @SayaliBThakare
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