Epidermal growth factor (EGF) as a novel treatment for neuro-regeneration
EGF is a novel treatment for neuro-regeneration with a dual mode of action by
1) stimulating myelin regeneration and
2) protecting nerve cells by beneficially regulating macrophage polarization.
These EGF properties have also recently been demonstrated with HB (Heparin-binding) -EGF (Linnerbauer et al., Nature Immunology 2024). EGF can therefore be indicated for the treatment of diseases with high unmet medical need such as:
• Multiple sclerosis (MS)-related optic-neuritis
• Clinically isolated syndrome and acute relapses of MS
• Progressive forms of MS
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Guillain Barre Syndrome (GBS)
• Possible indication extension such as Alzheimer disease and Parkinson’s disease
Lead Products ACR101 and ACR102 are derived from Epidermal Growth Factors
EGF is a natural peptide present in several tissues where it participates in specific developmental processes. EGF penetrates the blood brain barrier (BBB) as intraperitoneal EGF induces the activity of spinal cord L-ornithine decarboxylase in rat experimental model.
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.
ACR101 & ACR102 act via macrophage M2 polarization as in other therapeutic indications
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 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.
HB-EGF produced by astrocytes has recently been shown to modulate neuro-inflammation (Linnerbauer et al, Nature Immunology, 2024).
These findings support ACR101 & ACR 102, derived from EGF, as treatments for neurodegenerative disorders such as Multiple Sclerosis, Optic-neuritis, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Guillain-Barre Syndrome (GBS) and Alzheimer’s disease.
Precursor ACR001 (EGF) decreases inflammation 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 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)
