Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment.
Kagistia Hana Utami, Nur Amirah Binte Mohammad Yusof, Jing Eugene Kwa and 3 others
PMID 32460900WHAT IT FOUND
In fragile X human neural cells grown in the lab, metformin corrected excess protein synthesis and reduced excessive progenitor proliferation, but it did not fix neurite growth deficits or correct Akt and ERK changes.
Key findings
01FMRP-deficient neural progenitors and neurons showed elevated de novo protein synthesis compared with control cells.
02Metformin at 0.5 mM normalized elevated protein synthesis in FMRP-deficient neurons, but did not normalize phosphorylated Akt or ERK.
03Metformin reduced excessive proliferation in FMRP-deficient neural progenitors, but did not rescue neurite outgrowth or branching deficits.
STILL TO COME
How it was doneWhat they found
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What it does not show
The work was done in stem-cell-derived human neural cells, not in people, so it does not show what metformin does in a patient. The study used one isogenic knockout embryonic stem cell pair and two fragile X induced pluripotent stem cell lines, which is a small set of cell models. The metformin concentrations were tested in cell culture and do not establish a clinical dose. The authors did not show how metformin normalized protein synthesis, because Akt and ERK phosphorylation remained elevated. The study did not test speech, cognition, behaviour or daily function, and it did not test a full range of fragile X-related deficits. At 1 mM, metformin reduced proliferating cells in control cultures as well as knockout cultures, so the dose may have broad effects on cell growth.
Declared interests
The study was supported by FRAXA Research Foundation, Strategic Positioning Fund for Strategic Orphan Diseases and SUREKids. The supplied text does not include an author conflict-of-interest declaration.
The easy way to misread this
Do not conclude that metformin is an effective treatment for fragile X symptoms. The study tested human neural cells in culture, not patients, and it did not correct neurite growth deficits or normalize Akt and ERK signalling.