Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations.
Inci S Aksoylu, Pauline Martin, Francis Robert and 10 others
PMID 37880800WHAT IT FOUND
In lab cells from a TSC patient, rapamycin failed to correct neural growth issues.
A newer drug, RMC-6272, reversed these cellular defects and fixed gene translation problems that rapamycin missed.
Key findings
01Rapamycin treatment did not reduce neurite number, length, or extremities in TSC1-null neural progenitor cells.
02The bi-steric mTORC1 inhibitor RMC-6272 significantly reduced neurite number, length, and extremities in TSC1-null cells.
03RMC-6272 reversed a subset of gene translation changes that remained insensitive to rapamycin.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study used cells from only one patient. The postmortem brain analysis included very few samples (6 ASD, 4 controls), limiting statistical power. Findings are from lab cells and postmortem tissue, not living patients. The new drug RMC-6272 was not tested in humans for TSC-related symptoms in this paper.
Declared interests
RMC-6272 was provided by Revolution Medicines, Inc. Funding came from NIH, Wellcome Trust, Swedish Brain Foundation, Swedish Research Council, and Wallenberg Academy Fellow program.
The easy way to misread this
Do not assume RMC-6272 is an available or proven treatment for TSC or autism. This study only tested the drug on cells in a lab dish and on brain tissue after death. It shows the drug works better than rapamycin at fixing specific cellular defects in a dish, but it does not prove it helps patients.