Peptides›Cognitive›BDNF (Brain-Derived Neurotrophic Factor)

BDNF (Brain-Derived Neurotrophic Factor)

/ Endogenous neurotrophin (TrkB receptor ligand); recombinant

TIER 3 · PreclinicalN = 0 · TESTING PENDINGMW 27000.00 g·mol⁻¹

ALIAS · Brain-derived neurotrophic factor · Recombinant methionyl human BDNF · r-metHuBDNF

—

Pass rate

Samples

Suppliers

Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

Terms in this page you can click for a plain-English popup: , , , , , , , .

§ A · Identity

Primary sequence— sequence not captured —

MW · 27000.00CLASS · Endogenous neurotrophin (TrkB receptor ligand); recombinantCATEGORY · Cognitive

Tier 3. No approved BDNF therapeutic. The Phase 2 ALS trial of recombinant methionyl human BDNF (BDNF Study Group 1999 Neurology) failed its primary endpoint. Multiple intracerebroventricular BDNF programs in Parkinson disease and other neurodegenerative indications were discontinued for lack of efficacy or delivery limitations. Robust preclinical biology has not translated to clinical benefit.

§ B · Mechanism of action

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, structurally related to NGF. The biologically active form is a non-covalent homodimer of the mature BDNF polypeptide (~13.5 kDa per monomer; dimer ~27 kDa). BDNF binds the TrkB receptor tyrosine kinase as its high-affinity partner and the p75 neurotrophin receptor at lower affinity. TrkB signalling activates Ras-MAPK, PI3K-Akt, and PLC-gamma cascades that drive neuronal survival, dendritic spine remodelling, and long-term potentiation — the molecular substrates of activity-dependent synaptic plasticity in the adult brain.

Endogenous BDNF expression and release are activity-regulated: neuronal firing, exercise, and antidepressant pharmacology all elevate BDNF in animal models. The endogenous biology is one of the most-cited in neuroscience; the translational pharmacology of administered BDNF protein is far less successful.

§ C · Human clinical evidence

Tier 3. The Phase 2 trial of subcutaneous recombinant methionyl human BDNF in ALS (BDNF Study Group, Neurology 1999) did not improve survival or function versus placebo. Intracerebroventricular BDNF programs in Parkinson disease did not advance to approval. No human clinical development of BDNF has produced a positive Phase 3 readout.

§ D · Primary literature

PubMed10227630BDNF Study Group et al. — A controlled trial of recombinant methionyl human BDNF in ALS: The BDNF Study Group (Phase III) · Neurology · human-phase-3-rctSubcutaneous recombinant methionyl human BDNF did not improve survival or pulmonary function versus placebo over nine months in amyotrophic lateral sclerosis.Limitations: Single trial; subcutaneous delivery may not have achieved CNS exposure; sensory adverse events common.1999

PubMed23254191Park H et al. — Neurotrophin regulation of neural circuit development and function · Nature Reviews Neuroscience · reviewComprehensive review of neurotrophin (NGF, BDNF, NT-3, NT-4) signalling in neural circuit development, activity-dependent plasticity, and behaviour.Limitations: Narrative review; not a quantitative synthesis.2013

PubMed8833445Lewin GR et al. — Physiology of the neurotrophins · Annual Review of Neuroscience · reviewFoundational review of neurotrophin physiology covering receptor signalling, neuronal survival and differentiation, and roles in development and adult plasticity.Limitations: 1996 narrative review; predates much of the translational disappointment in human BDNF/NGF trials.1996

§ F · Safety signal

In the ALS Phase 2 trial, subcutaneous BDNF was associated with injection-site reactions and sensory side effects consistent with neurotrophin action on peripheral sensory neurons. CNS delivery has been complicated by short half-life, poor blood-brain-barrier penetration, and limited diffusion in brain parenchyma.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The translational gap between BDNF preclinical biology and human therapeutic effect is a defining problem of the neurotrophin field. Delivery (BDNF protein does not cross the BBB), pharmacokinetics (short half-life, restricted parenchymal distribution), and downstream feedback regulation of TrkB signalling have all been implicated. Vendor 'BDNF' protein for research use has no human clinical evidence base and should not be conflated with hypothetical therapeutic BDNF; small-molecule TrkB agonist programs (e.g. 7,8-DHF in academic literature) are pharmacologically distinct.