NeuroScientific Biopharmaceuticals Ltd (ASX: NSB) has received positive results from a recently completed assessment of lead drug candidate EmtinB.
Human primary cell-based systems modelling of autoimmune disease showed that EmtinB significantly reduced inflammatory cytokines Interleukin (IL)-17A, IL-17F, and IL-6. These cytokines are strongly associated with multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, and ankylosing spondylitis and play a prominent role in the damaging inflammatory responses seen in Multiple sclerosis (MS) and Alzheimer’s disease (AD).
Managing Director and CEO, Matt Liddelow, said down regulation of the production of IL-17A, IL-17F, and IL-6 significantly supports the disease-modifying effect of EmtinB as a treatment for these neurodegenerative conditions. The study was undertaken by leading independent contract research organisation Eurofins, Missouri USA.
“These impressive results reinforce the multi-faceted therapeutic potential of EmtinB as a disease-modifying treatment for both Multiple sclerosis and Alzheimer’s disease.
“While chronic inflammation is central to disease pathology of Multiple sclerosis, inflammatory responses are thought to be a secondary cause of neurodegeneration in Alzheimer’s disease.
“Therefore, EmtinB has the potential to positively influence neuroprotection, neuroregeneration, and the inflammatory environment that acts to exacerbate tissue damage in these neurodegenerative conditions.
“Please also note that the company is in the final stages of preparations for the submission of its safety data for ethics approval for commencement of a first-in-human Phase I study of Emtin and further updates will be provided in the coming weeks.”
IL-17A, IL-17F, and IL-6 are chemical signalling compounds called cytokines that induce inflammation and play a key role in protecting the body from invading pathogens. IL-17A and IL-17F are produced by activated T cells (Th17) of the adaptive immune system and stimulate the production of other cytokines (IL-1β, TNF, and IL-6) by various cell types.4 IL-6 helps regulate the inflammatory response by acting on Th17 cells.5
In chronic inflammation, dysfunctional production of IL-17A and IL-17F by Th17 immune cells upregulates production of IL-1β, TNF, and IL-6 leading to overstimulation of the immune system and the destruction of tissue (Figure 1). IL-17A and IL-17F have been recognised as key drivers of chronic inflammatory and autoimmune diseases. Targeting IL-17A has been a successful strategy in the development of approved drugs for the treatment of psoriasis and compounds that block IL-6 activity have been successfully approved for the treatment of rheumatoid arthritis.6
Regulating Inflammation
EmtinB binds to a receptor called the low-density lipoprotein receptor-related protein (LRP)-1 that is present in nerve cells and activates pathways within these cells that enhance survival and regeneration after injury.7 LRP-1 is also expressed by a number of cell types involved in inflammatory processes and has been shown to modulate inflammation in neurodegenerative diseases including in AD and MS.8
In addition to its expression in nerve cells, LRP-1 is present in cells of other tissues of the body and is positively associated with reducing the inflammatory environment in diseases of the kidney, lung, and heart.
The results from this current study are further evidence of the role LRP-1 plays in regulating inflammation in tissues found outside the central nervous system (CNS) and are fundamentally important in linking EmtinB activation of LRP- 1 to a downstream reduction in key cytokines (IL-17A, IL-17F, and IL-6) that are known to drive inflammatory processes of chronic inflammation and autoimmune diseases.