FGL

A synthetic pentadecapeptide (sequence: EVYVVAENQQGKSKA) derived from the FG loop of the second fibronectin type III module of Neural Cell Adhesion Molecule (NCAM). The N-terminal glutamate is modified to pyroglutamic acid in the functional form. Critically, FGL is biologically active only as a tetrameric dendrimer — four peptide copies coupled to a lysine backbone — because FGFR1 activation requires receptor dimerization.

Developed by Elisabeth Bock and Vladimir Berezin at the University of Copenhagen, and commercialized by Enkam Pharmaceuticals A/S. A Phase I intranasal safety trial in 24 healthy volunteers was completed (Anand et al., 2007), but no efficacy trials have been conducted and clinical development appears to have stalled after an EU-funded grant period (~2012).

FGL has an extensive preclinical record across multiple species (rats, mice, gerbils, dogs, primates). Cambon et al. (2004) showed a single ICV injection enhanced memory consolidation for over one month. Knafo et al. (2012) demonstrated FGL facilitated AMPA receptor synaptic delivery via PKC-CaMKII signaling, nearly doubling LTP in hippocampal CA1 neurons.

Anti-inflammatory effects are mediated through neuronal CD200 upregulation and IGF-1 release. Klein et al. (2016) showed endogenous neural stem cell mobilization after stroke. A Phase I trial (Anand et al., 2007, n=24 healthy males) confirmed intranasal safety and tolerability at 25-200 mg. The 6 million Euro EU-funded NeuroFGL project (~2012) supported further development, but no Phase II or efficacy trials have been reported. Clinical development appears stalled.