Nature Medicine – Perioperative IDH inhibition in IDH-mutant glioma www.nature.com/articles/s41...
Excited to see the updated results from INDIGO confirming sustained benefit of mIDH inhibition for 1st line treatment in patients with G2 gliomas. Reduced seizure frequency aligns with our findings that mIDH inhibition modulates the glioma electrical microenvironment! 👇
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
So incredibly proud of my team and our collaborators.
What a fantastic step forward for brain cancer clinical trials and mIDH inhibitors
@braincancerlab @jimwhittle.bsky.social @saskiafreytag.bsky.social
@wehi-research.bsky.social
www.nature.com/articles/s41...
Researchers from WEHI, the Royal Melbourne Hospital & @petermaccc.bsky.social have achieved a brain cancer clinical trial world-first, providing hope to patients with low-grade gliomas.
🔗 www.wehi.edu.au/news/world-f...
@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
A central question in neuro-oncology is whether therapies penetrate the tumour and exert a biological effect.
@jimwhittle.bsky.social and colleagues developed BrainPOP, a perioperative clinical trial platform and our lab had the pleasure of leading the translational research.
1/8
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
