VPCnt-101 — Oral Anti-Neuroinflammatory Treatment
The First Effective Treatment for Inflammatory Disease Initiated by Neurotrauma
VPCnt-101 is the first effective treatment of the severe, destructive inflammatory disease initiated by neurotrauma and by stroke. Discovered and developed by VPC NeuroTherapeutics Inc.
What an Effective Treatment Requires
The inflammatory disease initiated by neurotrauma is severe, destructive, and very protracted. An effective treatment requires a powerful anti-inflammatory agent that crosses the blood-brain barrier and that can be administered continuously for 8 weeks.
Xanthohumol: A Known Anti-Inflammatory With a New Application
Xanthohumol is a small flavonoid molecule (356 Da) naturally found in hops — the same plant used in beer production. Its anti-inflammatory properties in tissues outside the central nervous system have been extensively documented in scientific literature. It is orally bioavailable, well-tolerated, and suitable for sustained dosing.What xanthohumol is
Dr. Jacek Kwiecien discovered that xanthohumol's known anti-inflammatory activity extends to the central nervous system. Using VPC's well-characterized rat model of spinal cord injury, he demonstrated that oral administration of xanthohumol produced a powerful anti-neuroinflammatory effect — inhibiting the severe inflammatory disease initiated by SCI. This anti-neuroinflammatory application is proprietary (USPTO 17,346,726).
The discovery
At an optimized dose, xanthohumol eliminated the inflammatory disease from the SCI lesion before week 8 post-injury — more than halving the disease duration compared to the 16+ weeks observed in untreated animals. Treated animals showed markedly fewer macrophages in the lesion, smaller lesion size, and greater preservation of surrounding spinal cord tissue — a clear neuroprotective effect.
The result
Mechanism of Action
Reduces Inflammation
Xanthohumol markedly reduces the number of macrophages in the injury lesion and accelerates their elimination. In preclinical studies, macrophage clearance was achieved within 8 weeks in treated animals — compared to more than 16 weeks in untreated controls.
Neuroprotective Effect
By reducing the inflammatory assault, xanthohumol protects spinal cord tissue surrounding the injury from progressive destruction. In treated animals, the lesion is markedly smaller and the preserved peri-lesional spinal cord area is significantly greater than in untreated controls.
Eliminates Vasogenic Edema
Inhibition of inflammation results in less damage to blood vessels, less leakage of fluid into surrounding tissue, and return of undamaged spinal cord to function — directly addressing the mechanism that causes paralysis.
Preclinical and Clinical Evidence
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Extensive preclinical studies demonstrated that both hop-derived and synthesized xanthohumol markedly reduce numbers of macrophages in the lesion and accelerate their elimination to within 8 weeks vs. more than 16 weeks in untreated SCI rats. The lesion in xanthohumol-treated SCI rats is markedly smaller and the peri-lesional area of the spinal cord is greater than in untreated rats. This amounts to a neuroprotective effect of xanthohumol.
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The optimal dose of xanthohumol established in preclinical studies was translated from the rat dose to the human dose and adjusted to body weight in individual patients. Dr. W. Dąbrowski used this dose in a small clinical study involving SCI patients.
9 of 9 treated patients improved, recovering motor function
MRI confirmed elimination of swelling from the spinal cord, indicating effective anti-inflammatory action
Untreated SCI patients never improved and had vasogenic edema in the spinal cord next to the vertebral fracture
(Dąbrowski, Kwiecien et al., manuscript in preparation)
VPCnt-101 — Oral Formulation With Xanthohumol
VPCnt-101 is an oral formulation with xanthohumol being developed by VPC NeuroTherapeutics Inc. for clinical trials, regulatory approvals, and market approval to treat disease initiated by SCI — an orphan disease in the USA and in the European Union. Subsequently, VPCnt-101 will undergo testing in clinical trials involving patients with TBI, with concussion, and with stroke.
VPC NeuroTherapeutics holds a Pre-Investigational New Drug file with the FDA (PIND 166668) for VPCnt-101 in the treatment of disease initiated by SCI.
Beyond Neurotrauma
Future Applications
Since a great majority of diseases of the aging brain — including neurodegenerative diseases and mood disorders — have inflammatory pathogenesis, it is anticipated that VPCnt-101 will be effective in treating these ailments. Specific clinical trials and regulatory approvals will follow.
Advancing Toward Clinical Trials
VPC NeuroTherapeutics is progressing VPCnt-101 through regulatory development as the first effective treatment for the severe, destructive inflammatory disease initiated by neurotrauma and by stroke.