Nature Medicine – Perioperative IDH inhibition in IDH-mutant glioma www.nature.com/articles/s41...

The Lancet Oncology – INDIGO trial www.thelancet.com/journals/lan...

A landmark research milestone, from a brilliant collaborative team, published in @natmed.nature.com

🔗 www.nature.com/articles/s41...

@sarahannbest.bsky.social @saskiafreytag.bsky.social tag.bsky.social @jimwhittle.bsky.social

@sarahannbest.bsky.social @saskiafreytag.bsky.social afreytag.bsky.social ‬ @jimwhittle.bsky.social whittle.bsky.social @natmed.nature.com edicine.bsky.social @wehi-research.bsky.social @petermaccc.bsky.social ‬

We would like to thank our amazing team, especially Kate Drummond, clinical and research collaborators and the patients in this trial. We are excited to expand our expertise and dive more deeply into what is driving response.
8/8

Yes! Our collaborators @Florey performed patch clamp electrophysiology on fresh tissue pre- and post-treatment and found a reduction in synaptic activity.
This is consistent with recently published results in a clinical trial of another mIDH inhibitor, where patients reported fewer seizures!
7/8

Spatially, neurons in the leading edge of tumours seemed to have a decrease in synaptic signalling pathway expression.
Could the mIDH inhibitor, or the resulting reduction in the metabolite 2-HG, be impacting neuronal activity?
6/8

Next: what happens transcriptionally when mIDH is inhibited? @montanaspiteri.bsky.social investigated the impacts on a single-cell level and found that the progenitor population became less differentiated following treatment.
5/8

Our first answer: the drug gets in! We can see from the spatial distribution of metabolite biomarker 2-HG that mIDH treatment markedly reduces 2-HG abundance throughout the tumour using spatial metabolomics with @sai22vinod.bsky.social and colleagues.
4/8

IDH-mutant glioma patients underwent a pre-treatment biopsy followed by one cycle of treatment and surgical resection of tumour.
We coordinated multi-omic analyses to interrogate drug activity in LGG, focusing on transcriptomic and metabolomic impacts of the drug, using the paired samples.
3/8

Today we’re excited to share the findings from the first clinical trial, mIDH inhibitor safusidenib in LGG, out today in Nature Medicine.
Read it here www.nature.com/articles/s41... and tweetorial below 👇
2/8

Next: what happens transcriptionally when mIDH is inhibited? @montanaspiteri.bsky.social investigated the impacts on a single-cell level and found that the progenitor population became less differentiated following treatment.
5/8

Our first answer: the drug gets in! We can see from the spatial distribution of metabolite biomarker 2-HG that mIDH treatment markedly reduces 2-HG abundance throughout the tumour using spatial metabolomics with @sai22vinod.bsky.social and colleagues.
4/8

IDH-mutant glioma patients underwent a pre-treatment biopsy followed by one cycle of treatment and surgical resection of tumour.

We coordinated multi-omic analyses to interrogate drug activity in LGG, focusing on transcriptomic and metabolomic impacts of the drug, using the paired samples.
3/8

Today we’re excited to share the findings from the first clinical trial, mIDH inhibitor safusidenib in LGG, out today in Nature Medicine.

Read it here www.nature.com/articles/s41... and tweetorial below 👇
2/8