Researchers working in a mice reported that an experimental drug, NTRX-07, may treat Alzheimer’s by targeting a potential cause — it was seen to ease brain inflammation in the animals by restoring the brain’s ability to remove clumps of the beta-amyloid protein that is a hallmark of the disease.
The excessive accumulation of the beta-amyloid protein in neurons promotes the onset of inflammatory processes in the brain, causing nerve cell damage and loss, and is thought responsible for such symptoms as cognitive deficits, memory loss and dementia.
“This drug may reduce inflammation in the brain, which is linked to Alzheimer’s disease,” Mohamed Naguib, MD, lead author of the study presented at the recent Anesthesiology 2016 meeting in Chicago, said in a press release. “NTRX-07 uses a different mechanism than many other Alzheimer’s drugs currently available, as it targets the cause of the disease, not just the symptoms.”
Researchers initially found that NTRX-07 could improve a chronic pain condition, called neuropathic pain, which is associated with sustained neuroinflammation. The team then investigated whether NTRX-07 also could ease inflammation in Alzheimer’s disease.
Using mice with Alzheimer’s-like neurodegeneration, researchers noted that the disease changes a type of immune cell present in the brain, called microglia. These cells typically remove beta-amyloid aggregates, but were unable to do so effectively in the Alzheimer’s mice, and the protein clumps accumulated.
Treatment with NTRX-07 was seen to decrease inflammation and protect neurons and brain regenerative cells, as well as restore memory abilities in the mice. Researchers found that NTRX-07 targets the CB2 receptors, a group of proteins present in microglia, activating these cells and strengthening their anti-inflammatory “cleaning” effect. The drug improved the removal of the beta-amyloid aggregates, with a positive impact on the animals’ memory performance and other cognitive skills.
NTRX-07 also stimulated the production of a protein called SOX2, which has been shown to help new brain cells develop. In Alzheimer’s disease, this protein is present in lower amounts than normal. Mice treated with NTRX-07 showed restored levels of SOX2, while untreated mice did not.
Naguib and Joseph F. Foss, MD, director of clinical research for general anesthesiology at the Cleveland Clinic, co-founded a company to continue developing NTRX-07. The company, with the support of the Alzheimer’s Drug Discovery Foundation and the Alzheimer’s Association, hopes to start a Phase 1 clinical trial next year.