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Cognitive & Neuroprotective

FGL(L) (FG Loop Peptide)

NCAM-derived research peptide that partially activates FGFR1 to support memory and neuroprotection in animal models.

InvestigationalEvidence level 2 of 5: Animal data, minimal humanAlso: FGL, FGLL, NCAM FG-loop peptide, Enreptin

Overview

FGL is a 15-amino-acid peptide copied from the FG loop of the neural cell adhesion molecule (NCAM), the region NCAM uses to engage fibroblast growth factor receptor 1 (FGFR1). By mimicking that contact, FGL partially activates FGFR1 and its downstream survival and plasticity pathways. In rats and mice it enhanced memory consolidation, promoted neurite outgrowth and synapse formation, reduced microglial inflammation and limited damage in models of Alzheimer's disease, stroke and brain injury. A Danish biotech advanced it into a small Phase 1 trial, which reported acceptable short-term tolerability, but development did not progress to efficacy trials. It should be regarded as an experimental compound with an essentially unknown human benefit-risk profile.

Classification
Synthetic 15-amino-acid peptide derived from the neural cell adhesion molecule (NCAM)
Route
Intranasal or subcutaneous
Half-life
Not well characterized in humans

Mechanism of action

Primary targetFGFR1 (partial agonist, NCAM-mimetic)
  1. Intranasal or SC deliveryPeptide reaches the brain; intranasal route used to improve CNS exposure.
  2. Binds FGFR1Mimics NCAM's FG-loop contact, partially activating fibroblast growth factor receptor 1.
  3. PI3K/Akt and MAPK signalingDownstream kinases promote neuronal survival and cytoskeletal growth.
  4. Neurite outgrowth, synaptogenesisDendrites extend and synapses form, especially in hippocampus.
  5. Microglial calmingPro-inflammatory microglial activation decreases in aged and amyloid models.
Downstream effects
  • Memory consolidation (animals)
  • Neuroprotection
  • Reduced neuroinflammation

Researched for

  • Alzheimer's disease models
  • Age-related memory decline
  • Traumatic brain injury
  • Stroke neuroprotection

Research notes

  • Rodent studies (Cambon 2004; Secher 2006) show improved spatial and social memory and synaptic plasticity.
  • Downer et al. reported reduced microglial activation and restored LTP in aged rats.
  • A Phase 1 study of the FGLL peptide in healthy volunteers assessed tolerability and pharmacokinetics only.
  • No controlled human efficacy data exist; real-world use is extrapolated from animal work.

Reported side effects

  • Nasal irritation (intranasal)
  • Injection-site reactions (SC)
  • Headache
  • Unknown long-term effects

Contraindications & cautions

  • Active malignancy (FGFR1 signaling is pro-proliferative)
  • Pregnancy and breastfeeding
  • Age under 18
  • Uncharacterized intracranial pathology

Lab monitoring

  • CBC, CMP
  • Vitamin B12, folate
  • Thyroid panel (TSH, free T4)
  • hsCRP
  • Baseline and follow-up cognitive assessment

Dosing and pricing for FGL(L) (FG Loop Peptide)

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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