EGF-Based Therapy:

Unlocking Neuroregeneration

EGF plays a direct role in myelin synthesis

EGF is a natural peptide that plays a crucial role in tissue development and repair, including the central nervous system (CNS).

How EGF drives neuroregeneration

  • EGF stimulates oligodendrocyte differentiation and maturation, a key step necessary for remyelination, as evident after CNS injury (Scalabrino, Front Neurol 2021). The remyelination effect of EGF has been shown by intraperitoneal administration of EGF in Multiple Sclerosis animal models.
  • Its mode of action relies on stimulating oligodendrocyte and Schwann cell differentiation and maturation which represent key steps necessary for remyelination. This is seen after CNS injury models. Also, the EGF gene is strongly activated in the repair phase following Theiler’s virus-induced demyelination in mice and the EGF mRNA synthesis is significantly increased in the corpus callosum during remyelination after cuprizone-induced demyelination.
  • Among its effects, EGF is the effector of the myelinotropic action of cobalamin (Cbl) and it positively regulates the myelinotropic PrPC protein synthesis which is essential for myelin maintenance.
EGF Platform Illustration

Clinical Relevance

EGF has shown efficacy in preclinical models. EGF can therefore be indicated for the treatment of diseases with high unmet medical need where EGF per se has shown preclinical efficacy such as:

  • Progressive forms of multiple sclerosis
  • Alzheimer’s disease
  • Huntington’s disease

But also, in:

  • Multiple sclerosis-related optic-neuritis
  • Clinically isolated syndrome and acute relapses of multiple sclerosis

Additionally, HB-EGF (a member of the EGF family) shows strong anti- inflammatory activity, providing further validation of EGFs therapeutic potential (Linnerbauer et al., Nature Immunology 2024).

ACR101 and ACR102 Illustration

EGF and neuroinflammation: A family business? The strong case for HB-EGF in EAE

Necrotizing enterocolitis in newborn babies can successfully be treated with EGF (clinical data), in addition, most of the patients with necrotizing enterocolitis have low salivary EGF levels; this observation is in line with decreased EGF levels seen in spinal cord of multiple sclerosis (MS) patients.

EGF prevents macrophage M1 polarization and promotes M2 polarization in experimental necrotizing enterocolitis. M2 macrophage polarization drives oligodendrocyte and Schwann cell differentiation during CNS nerve remyelination and it appears that M2 cell polarization is essential for efficient remyelination and to decrease inflammation in MS and Alzheimer’s disease.

Heparin-binding EGF-like growth factor (HB-EGF), that belongs to the EGF family, is produced by astrocytes to modulate neuro-inflammation and its intranasal administration prevents EAE (Linnerbauer et al., Nature Immunology 2024)

HB-EGF also exerts anti-inflammatory properties including polarization of macrophages toward the M2 phenotype (Wei and Besner, J Surg Res 2015) M2 macrophage polarization is observed with drugs effective in EAE and approved for MS such as glatiramer acetate and IFN-beta (Luo et al, Front Immunol 2024)

Macrophage M2 Polarization

EGF decreases inflammation, reduction of clinical symptoms and induces remyelination in the MOG-EAE model of MS

EGF administered subcutaneous every other day is efficacious against clinical signs in the MOG-induced experimental autoimmune encephalomyelitis (EAE) model (the reference treatment is dexamethasone). In addition, the MOG-induced EAE mouse brain shows clear signs of remyelination when treated with EGF (Luxol fast blue stained sections of spinal cord). Another conclusion is that the EGF injected in the periphery acts directly in the brain, supporting its BBB passage (Nicoletti et al, J Neuroimmunology 2019)

MOG-EAE Model Results
MOG-EAE Model Results
Back to Home