Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation.
Mouhamed Alsaqati, Vivi M Heine, Adrian J Harwood
PMID 33076974WHAT IT FOUND
Neurons from one TSC2 patient showed high excitability but poor network synchronisation.
Rapamycin lowered excitability but did not fix the network. A ULK1 activator restored synchronisation in the dish, suggesting a new target for TSC-related brain issues.
Key findings
01TSC2 patient neurons exhibited increased spontaneous firing rates and burst numbers compared to controls, but a significant reduction in synchronised burst frequency.
02Chronic or short-term treatment with rapamycin decreased neuronal hyperexcitability but failed to improve network synchronicity or connectivity.
03Treatment with the ULK1 activator LYN-1604 significantly increased synchronised bursts to control levels and improved neuronal spatial connectivity.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
Read the rest of this summary
You get three full summaries a month, free, and we do not ask for a card. Search, the TL;DRs and your library stay unlimited either way.
What it does not show
The findings are based on neurons derived from a single patient, so they may not represent the broader TSC2 population. The study was conducted entirely in a dish (in vitro); it does not demonstrate clinical improvement in patients. The exact mechanism of how LYN-1604 restores connectivity in a living brain is unknown. Data distribution was assumed to be normal but not formally tested.
Declared interests
The authors declared no competing interests. The work was supported by non-US government funding.
The easy way to misread this
Do not interpret the restoration of network synchronicity in the dish as evidence that LYN-1604 is a ready-made treatment for autism or TSC. This is a pre-clinical study using neurons from one patient; the drug has not been tested for safety or efficacy in humans for this purpose.