$1.7M Grant Given to Move Therapy Targeting Cannabinoid Receptor into Clinical Trials in Alzheimer’s Patients

NeuroTherapia, a Cleveland Clinic spin-off biotech company, has received a $1.7 million funding commitment from the Alzheimer’s Drug Discovery Foundation to advance its lead drug candidate NTRX-07 — a selective cannabinoid type 2 (CB2) receptor agonist that can be orally administered — toward human clinical trials.

This therapy targets a cannabinoid receptor in the brain,  a new approach for treating Alzheimer’s and other neurologic diseases. Cannabinoid receptors are the same ones that are targeted in medical marijuana therapy, but NTRX-07 is not a cannabis (marijuana) derivative.

Immune cells, including microglia within the central nervous system (CNS), express CB2 receptors. (Microglia are a type of glial cell located throughout the brain and spinal cord that from part of the central nervous system and are the primary immune cells of that system, acting as the main inflammatory cell type in the brain.)

NeuroTherapia reports that CB2 receptors on microglia, when activated, can modulate immune cell migration and cytokine release, thereby decreasing pro-inflammatory responses, and that the ideal therapeutic candidate will have high affinity for the CB2 receptor while avoiding the adverse psychotropic effects (i.e., getting high) that accompany cannabinoid type 1 (CB1) receptor-based therapies. NTRX-07 is also able to penetrate the blood-brain barrier, providing for high expression levels in the CNS. Consequently, CB2 receptors have become the subject of research as a potential therapeutic target to treat various neuro-inflammatory disorders.

NTRX-07, developed as a potent and selective CB2 receptor agonist that can be orally administered, has shown capacity to lessen neuroinflammation in preclinical disease models, thereby protecting neurons from damage and death. The company also reported that multiple preclinical studies have demonstrated NTRX-07’s ability to promote neuronal survival through decreasing pro-inflammatory microglial activity, with its efficacy having been established in multiple neuropathic pain models, including chemotherapy-induced peripheral neuropathy (CIPN), nerve ligation, and complex regional pain syndrome (CRPS) induced by ischemic injury.

Mohamed Naguib and Joseph Foss, founders of NeuroTherapia. (Photo courtesy of Alzheimer’s Drug Discovery Foundation)

Moreover, NeuroTherapia said NTRX-07 has been shown to improve memory loss observed in Alzheimer’s disease rodent models, and that no in vivo toxicology or psychomimetic effects have been observed. NeuroTherapia has initiated IND-enabling studies with the goal of initiating the human clinical trials of NTRX-07 in mid-2017.

“The protection of neurons from the damaging effects of inflammation caused by microglial over-activation is a novel approach to treating Alzheimer’s disease,” Joseph Foss, director of Clinical Research for General Anesthesiology at the Cleveland Clinic, and co-founder and chief medical officer of NeuroTherapia, said in a press release. “We are excited to be partnering with the ADDF on the development of NTRX-07 for this devastating disease.”

Multiple preclinical studies published by Mohamed Naguib, a professor of Anesthesiology at the Cleveland Clinic Lerner College of Medicine, and co-founder and chief scientific officer of NeuroTherapia, have demonstrated that NTRX-07 reduces neuroinflammation caused by microglia, limiting the progression of Alzheimer’s disease, and that treatment with the compound in mice restored cognition, memory and synaptic plasticity — a key foundation of learning and memory. With the announced funding from the ADDF, NeuroTherapia will complete regulatory studies needed to initiate a clinical trial.

“The Alzheimer’s Drug Discovery Foundation is committed to supporting new therapeutic approaches with the most potential to impact Alzheimers and other causes of dementia,”  Howard Fillit, MD, the geriatrician and neuroscientist who has led the ADDF since its founding as its executive director and chief science officer, said in the release. “Drugs that combat neuroinflammation are a major part of our research portfolio, and we look forward to working with the team at NeuroTherapia to advance NTRX-07.”

NeuroTherapia was created by Cleveland Clinic Innovations to advance the research of Drs. Naguib and Foss, who are working to develop drugs that focus on microglia. These central nervous system immune cells can promote inflammation in the brain — a hallmark of Alzheimer’s, Parkinson’s, Huntington’s, and other neurodegenerative diseases.

Alzheimer’s disease is the only top 10 cause of death that cannot be prevented, cured or slowed, affecting an estimated affects 44 million people globally.

Sources:
Alzheimer’s Drug Discovery Foundation
NeuroTherapia, Inc.
Cleveland Clinic