The trial is currently recruiting in different sites across Australia. More information can be found here.
Instead of targeting amyloid plaques — or clumps of misfolded proteins — in the brains of Alzheimer’s patients, XPro1595 is designed to inhibit neuroinflammation, an earlier step in the disease. Neuroinflammation has been linked to the loss of neuronal communication, neuronal cell death, cognitive impairment, and plaque formation.
Occurring in the central nervous system, which consists of the brain and spinal cord, neuroinflammation is a key event underlying AD. It is mediated by an excessive activation of glial cells — nerve cells that surround and support neurons — and the overproduction of small pro-inflammatory molecules called cytokines.
The levels of tumor necrosis factor (TNF), a pro-inflammatory cytokine, are often increased in people with Alzheimer’s. XPro1595 is an investigational anti-inflammatory therapy that blocks inflammation by selectively neutralizing soluble tumor necrosis factor (sTNF).
Preclinical results in a mouse model of Alzheimer’s have shown that XPro1595 can help decrease neuroinflammation and amyloid beta accumulation triggered by a diet high in sugar and fats.
“This is a significant milestone for INmune Bio and for a field desperate for novel approaches to treat approximately 50 million people suffering from Alzheimer’s worldwide,” C.J. Barnum, PhD, director of neuroscience at INmune Bio, said in a press release.
“This approach to fighting one of the most devastating diseases of our time, which differs from current therapies targeting amyloid plaques, could be a key to cracking the code of Alzheimer’s disease,” said R.J. Tesi, INmune Bio’s CEO.
This new therapy works by selectively inhibiting the soluble form of TNF — that which is released into the bloodstream — and not its membrane-bound form, which remains attached to the membranes of immune cells. Since this last form is required to support neurons, fight off infections, and destroy cancerous cells, it is believed that XPro1595 will not have the unwanted side effects of currently approved TNF inhibitors, such as infection and cancer.
“XPro1595 targets the dysfunctional immune system that gives rise to chronic neuroinflammation in Alzheimer’s patients. The goal of this Phase Ib study is to demonstrate that XPro1595 is safe and can reduce neuroinflammation,” Barnum said.
The trial will test the safety, tolerability, and efficacy of XPro1595 in 18 adult patients with mild-to-moderate Alzheimer disease and evidence of peripheral inflammation. Three different doses of XPro1595 — 0.3, 1, and 3 mg/kg — will be administered via subcutaneous (under-the-skin) injection once a week for 12 weeks.
The presence of inflammation will be determined by measuring the levels of high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines in the blood and cerebrospinal fluid (CSF), which surrounds the brain and spinal cord. CRP is produced by the liver in response to systemic inflammatory mediators like soluble TNF alpha. The words “high-sensitivity” refer to a special test that measures very low levels of CRP.
The trial’s primary goal is identifying the presence of adverse events during treatment. Secondary goals include changes in the levels of CRP, inflammatory cytokines, amyloid beta and tau in the blood and CSF. Cognitive and neuropsychiatric symptoms also will be measured during the trial.
Importantly, this study will help identify the dose of XPro1595 to be used in a larger Phase 2 study.
“Neuroinflammation is one of the most exciting targets to slow or stop the progression of the cognitive and psychiatric symptoms of Alzheimer’s patients and improve their overall quality of life,” said Malú Tansey, PhD, a professor of neuroscience and director of the Center for Translational Research in Neurodegenerative Disease at the University of Florida College of Medicine.
“However, it’s not enough to block inflammation, anti-inflammatory strategies must take into account the support immune cells provide neurons,” Tansley added.
“By exclusively targeting sTNF, we should avoid the side effects, such as infection and cancer, commonly associated with currently approved TNF inhibitors,” he said.