FGF-1

A 155-amino-acid human growth factor that activates every FGF receptor in a heparin-dependent manner, studied in angiogenesis, wound-healing, and nerve-repair trials that never reached approval and sold almost exclusively as a laboratory reagent.

Also referenced as: FGF1, Acidic Fibroblast Growth Factor, aFGF, FGF-alpha, Heparin-Binding Growth Factor 1, HBGF-1, Fibroblast Growth Factor 1, NV1FGF, Riferminogene pecaplasmid, XRP0038, TTHX1114

Also appears in: Cardiovascular

What is FGF-1?

FGF-1 — acidic fibroblast growth factor, the founding member of the fibroblast growth factor family — is a native human protein of 155 amino acids (about 17.5 kDa) encoded by the FGF1 gene. It is worth being precise about what that means in a market built around short synthetic peptides: FGF-1 is a full recombinant protein folded into a β-trefoil, not a chain of a dozen residues assembled on a synthesizer. The 155-residue figure is the full translated sequence; residues 2–15 are removed as a propeptide, so the mature protein is the 140-amino-acid residue 16–155 form (roughly 15.8 kDa), and that mature form is what most research-grade preparations supply. Separately, the clinical protein programs used a genuinely truncated construct labeled FGF-1(1-141).

It appears in growth-factor discussions for two reasons. First, it is the one true generalist in the family. The human FGF family has twenty-two genes, but four of them — FGF11 through FGF14 — are intracellular proteins that never engage a receptor; of the eighteen secreted FGFs that do signal through FGF receptors, FGF-1 is the only one that activates every principal receptor isoform. That made it the obvious candidate whenever someone wanted to switch on FGF signaling broadly (Ornitz et al., Journal of Biological Chemistry, 1996;271(25):15292–15297). Second, that breadth produced a decades-long run of angiogenesis and tissue-repair programs — cardiac, limb, spinal cord, corneal — none of which produced an approved product. In practice FGF-1 reaches buyers as a cell-culture reagent sold by life-science protein suppliers, not as an injectable vial in peptide catalogs, where the “FGF” that actually shows up is almost always FGF-2 or an FGF21 analog.

How it works

• Universal FGF receptor agonist. FGF-1 binds and activates all seven principal FGFR splice variants (FGFR1b/1c, 2b/2c, 3b/3c, and 4), a promiscuity no other FGF shares. Receptor dimerization drives tyrosine autophosphorylation and the downstream RAS–MAPK, PI3K–AKT, PLCγ, and STAT cascades that push endothelial cells, fibroblasts, and keratinocytes toward proliferation and migration (Ornitz et al., Journal of Biological Chemistry, 1996;271(25):15292–15297; Zhang et al., Journal of Biological Chemistry, 2006;281(23):15694–15700; Ornitz & Itoh, WIREs Developmental Biology, 2015;4(3):215–266).
• Heparan sulfate is a required cofactor, not an additive. Cell-surface heparin-like molecules must be present for high-affinity FGF–FGFR binding; the glycosaminoglycan is a structural component of the signaling complex that also protects the protein from thermal denaturation and proteolysis. Without heparin or heparan sulfate, FGF-1 loses activity quickly (Yayon et al., Cell, 1991;64(4):841–848; Beenken & Mohammadi, Nature Reviews Drug Discovery, 2009;8(3):235–253).
• It has no signal peptide and exits cells by a non-classical route. FGF-1 is not secreted through the endoplasmic reticulum–Golgi pathway. Release is stress-triggered and depends on copper-dependent assembly of a multiprotein complex including S100A13 and a synaptotagmin fragment — one reason endogenous FGF-1 availability is tied to tissue injury rather than steady secretion (Landriscina et al., Journal of Biological Chemistry, 2001;276(27):25549–25557).
• A separate metabolic signaling arm, characterized almost entirely in animals. Fgf1 is a PPARγ target induced in adipose tissue by high-fat feeding, and FGF1-null mice develop an aggressive diabetic phenotype on a high-fat diet despite being normal on a standard one (Jonker et al., Nature, 2012;485(7398):391–394). Pharmacologically, a single parenteral dose of native recombinant FGF1 produced potent, insulin-dependent glucose lowering without hypoglycemia in diabetic mice, and chronic dosing produced whole-body insulin sensitization (Suh et al., Nature, 2014;513(7518):436–439) — the “endocrinization” in that paper’s title refers to FGF1 behaving like a metabolic hormone when delivered systemically, not to any protein engineering. A single intracerebroventricular injection of FGF1 induced sustained remission of hyperglycemia in diabetic rodents (Scarlett et al., Nature Medicine, 2016;22(7):800–806). No controlled human trial has tested any of it.

Research status

FGF-1’s clinical record is long, well-documented, and almost uniformly unsuccessful. No FGF-1 product is approved by the FDA or, to our knowledge, by any other regulator.

Cardiac angiogenesis: a small, controlled start that led nowhere. The first human use was intramyocardial injection of recombinant FGF-1 (0.01 mg/kg) alongside internal mammary artery grafting. Contrary to how this study is often summarized, it was double-blind and randomized: 40 patients with three-vessel disease were allocated to FGF-1 (n=20) or to heat-denatured FGF-1 as control (n=20), and digital subtraction angiography at 12 weeks showed capillary networks around the injection sites in the treated group (Schumacher et al., Circulation, 1998;97(7):645–650). A three-year follow-up of the same cohort reported ejection fraction rising from 50.3% to 63.8% with FGF-1 versus 51.5% to 59.4% in controls, with no accelerated atherosclerosis (Pecher & Schumacher, Annals of Thoracic Surgery, 2000;69:1414–1419). The real limits are scale and endpoint quality — twenty treated patients at a single center, with an angiographic surrogate rather than a hard clinical outcome as the primary readout — not an absence of controls. One durable oddity: the 1998 abstract itself glosses “FGF-I” as basic fibroblast growth factor, a naming slip that has propagated through secondary literature ever since.

Limb ischemia: the program that actually reached phase 3, and failed. Sanofi developed NV1FGF (riferminogene pecaplasmid, XRP0038), a plasmid driving local FGF-1 expression after intramuscular injection. In the phase 2 TALISMAN 201 trial, 125 patients with non-healing ulcers from critical limb ischemia were randomized to NV1FGF or placebo. The primary endpoint — complete healing of at least one ulcer at week 25 — was missed outright: 19.6% versus 14.3%, p=0.514. What generated enthusiasm was a secondary finding, a roughly twofold reduction in major amputation (HR 0.371; p=0.015) (Nikol et al., Molecular Therapy, 2008;16(5):972–978). The phase 3 TAMARIS trial was designed to confirm exactly that secondary signal in 525 patients across 171 sites in 30 countries. It did not: major amputation or death at one year occurred in 36% of the NV1FGF group versus 33% of placebo (HR 1.11, 95% CI 0.83–1.49; p=0.48), with no significant safety issues recorded (Belch et al., Lancet, 2011;377(9781):1929–1937; NCT00566657). The program ended there.

Spinal cord injury: terminated at interim analysis. BioArctic’s SC0806 combined FGF-1 with a biodegradable device implanted at the injury site in patients with complete traumatic spinal cord injury, in a phase 1/2 study (NCT02490501). At the November 2019 interim analysis the study missed its primary efficacy endpoint — no treated patient showed the electrophysiological signal of conduction across the injured segment — and secondary endpoints covering motor function and quality of life were unconvincing. The company stopped enrollment and discontinued the indication; the registry entry was eventually closed out as completed in 2025, with ten participants.

Recombinant FGF-1 protein programs that never enrolled. A US developer (CardioVascular BioTherapeutics, later Venturis Therapeutics) registered FGF-1(1-141) for coronary heart disease in 2005 (NCT00117936, phase 2, 150 planned) and for peripheral arterial disease in 2007 (NCT00424866, phase 1/2, 24 planned). Both are still listed as not yet recruiting roughly two decades later, with projected start dates that have been pushed repeatedly into the future — as of the latest registry update, 2027 and 2028 respectively. The one study in that program that did run — topical FGF-1 for diabetic or venous stasis ulcers (NCT00425178) — was a phase 1 enrolling eight patients, completed in 2006, with no published results.

Where FGF-1 chemistry is still active: engineered variants in the eye. The most credible modern work uses TTHX1114 (NM141), a thermostable engineered FGF-1 derivative given as an intracameral injection for corneal endothelial dystrophy, developed by Trefoil Therapeutics. Preclinical work showed accelerated regeneration of the corneal endothelial layer in donor human corneas in organ culture after Descemet stripping, with about 81% of the stripped area healed at 14 days versus 30% untreated (Pizzuto et al., Cornea, 2023;42(2):232–242). The sponsor has since reported results from a 22-patient phase 1/2 study (NCT04520321) and a 41-patient phase 2 study (NCT04812067) describing dose-dependent recovery of central corneal thickness and faster visual acuity recovery after Descemet stripping only. These are sponsor-reported results in a small program, and nothing has been approved. Note also that TTHX1114 is an engineered analog, not native FGF-1.

Small and unreported studies. An open-label pilot of intranasal FGF-1 in four patients with Parkinson’s disease was registered in 2022 (NCT05493462) and has not been updated since; its status is listed as unknown and no results have been published. A 24-patient study of ultrasound-guided recombinant FGF-1 injection (as ES135) for carpal tunnel syndrome completed in Taiwan in 2025 (NCT06328166); it carried no phase designation and results are not yet published.

What does not exist — and what exists only as a press release. There are no registered controlled trials of FGF-1 for tendon or muscle recovery, general tissue repair in healthy people, or anti-aging, and the peer-reviewed metabolic literature on FGF-1 is entirely animal work. But “no published human data” is not the same as “nothing is being administered to humans.” Zhittya Genesis Medicine has announced dosing more than 200 people with intranasal FGF-1 for Parkinson’s disease since 2022 and running a 100-person type 2 diabetes study, reporting outcomes such as motor-score and blood-glucose improvements. Apart from the four-patient pilot at NCT05493462, those programs are not on ClinicalTrials.gov, are not described as randomized or controlled, have produced no peer-reviewed publication, and have been run substantially outside the United States on a pay-to-participate basis reported at roughly $50,000 per participant. That body of claims should be treated as unverified, and it is not evidence that the rodent metabolic findings translate.

Common dosage forms

• Lyophilized recombinant protein in vials, the dominant format: research- or cell-culture-grade human FGF-1 expressed in E. coli, typically supplied as the mature residue 16–155 (140-amino-acid, ~15.8 kDa) form in microgram fills — commonly 10 µg, 50 µg, 100 µg, sometimes up to 1 mg — carrier-free or with a BSA carrier, labeled for research use only.
• Heparin-paired culture formulations, since the protein is routinely used with heparin in media to keep it stable and active.
• Investigational clinical presentations that were never marketed: sterile solution for intramyocardial or intramuscular injection, a topical wound formulation, an intracameral ophthalmic injection of an engineered variant, plasmid DNA for intramuscular injection (NV1FGF), a growth-factor-loaded biodegradable implant (SC0806), and an intranasal solution used in small and largely unregistered studies.
• No FDA-approved dosage form, no compounded pharmacy presentation, and no established cosmetic ingredient identity. The “FGF” that appears on cosmetic labels is generally FGF-2 under the INCI name sh-Polypeptide-1, which is a different protein.

This section describes formats only and is not dosing guidance.

Key considerations

• The regulatory record is a series of closed doors, not an open question. One phase 3 trial has ever been run on an FGF-1 therapeutic, and it was negative on its primary endpoint. Two protein programs registered in the mid-2000s have never enrolled a patient. One neurological program was stopped at interim analysis. Research-grade recombinant protein is a laboratory reagent manufactured for cell culture — it is not a sterile drug product and carries no clinical quality standard.
• A universal FGFR agonist is a proliferation and angiogenesis signal, and that pathway is an oncology target. FGFR signaling is aberrantly activated across several cancers, and approved FGFR-inhibitor drugs — erdafitinib, pemigatinib, futibatinib — exist specifically to shut it down. Deliberately administering a ligand that activates all FGFR isoforms runs that pathway in the opposite direction. The angiogenesis literature has treated this as a live theoretical concern throughout; the trials that ran were short, local, and in patients with no remaining revascularization options.
• The molecule is fragile, and every serious program worked around that. Native FGF-1 is thermally labile and protease-sensitive with a short functional half-life unless heparin or heparan sulfate is present. That is precisely why the clinical programs reached for plasmids, implanted devices, and engineered thermostable variants rather than simply injecting the protein — an important signal about how much of the promising work depends on the delivery engineering rather than the protein itself.
• The metabolic findings are real but do not transfer. The Nature and Nature Medicine results on insulin sensitization and diabetic remission are genuine and well-cited, and they used native recombinant FGF1 rather than engineered analogs, which makes them more interesting rather than less. But they are rodent studies, and the most striking of them required injection directly into the brain’s ventricles. None of it implies anything about a protein administered peripherally — or sprayed into the nose — in a human.
• Naming collisions are severe with this compound. FGF-1 (acidic) is constantly confused with FGF-2 (basic FGF, trafermin), the FGF marketed in Japan as Fiblast Spray for skin ulcers and burns and used in cosmetics — the 1998 Circulation abstract makes this exact error. FGF-1 is also unrelated to the FGF21 analogs (efruxifermin, pegozafermin) that dominate current metabolic pipelines, and to Generx/Ad5FGF-4, an FGF-4 gene therapy. In gene databases the alias ECGF is carried by both FGF1 and TYMP (thymidine phosphorylase, whose aliases also include ECGF1) — two completely unrelated proteins — so literature searches on that synonym return two disconnected bodies of work.