TSC patient-derived isogenic neural progenitor cells reveal altered early neurodevelopmental phenotypes and rapamycin-induced MNK-eIF4E signaling.
Pauline Martin, Vilas Wagh, Surya A Reis and 8 others
PMID 31921404WHAT IT FOUND
In TSC patient-derived neural progenitor cells, TSC1 loss enlarged cells, increased proliferation and neurite outgrowth.
Rapamycin reduced cell size but did not reverse increased proliferation or neurite outgrowth, and raised a protein-translation pathway. This is a cell model, not evidence for therapy.
Key findings
01TSC1 loss made neural progenitor cells larger and increased mTORC1 signaling, but rapamycin did not reverse their increased proliferation or neurite outgrowth.
02Heterozygous and homozygous TSC1 loss increased proliferation and neurite number and length in neural progenitor cells compared with corrected wild-type cells.
03Rapamycin blocked mTORC1 signaling but increased ERK and eIF4E phosphorylation in mutant neural progenitor cells.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study used cells in a laboratory, not people with TSC, so it does not show clinical effects on behavior, learning, movement, or communication. The cells came from a TSC patient with a TSC1 mutation, so they may not represent people with other TSC1 or TSC2 mutations. Rapamycin was tested only in cells, so the lack of effect on proliferation and neurite outgrowth does not mean it will not affect symptoms in patients. The authors did not show that the changed genes caused the cell phenotypes or that the gene changes produce protein changes. The paper reports laboratory signaling and gene-expression results, not therapy outcomes, so it cannot guide treatment decisions directly.
Declared interests
The funding section names the U.S. Army Materiel Command and the National Institute of Neurological Disorders and Stroke. The supplied text does not report author conflicts or commercial sponsorship.
The easy way to misread this
Do not read this as evidence that rapamycin should be stopped or changed in patients with TSC. The study tested cells in a dish, not people, and it did not assess clinical symptoms or therapy outcomes.