Targeting Neuroinflammation as a Novel Approach in Brain Health for Alzheimer Disease: RJ Tesi, MD

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"In other words, you want to treat someone with a drug that gets rid of bad inflammation, but doesn't completely turn off inflammation because the immune system has to participate in the repair and remodel of the brain that occurs with Alzheimer disease."

In the field of Alzheimer disease (AD), imaging techniques are rapidly advancing to effectively assess microstructural changes in the brain. In recent research, imaging results have uncovered indications of target engagement in gray matter cortices, which are widely recognized as the regions most impacted by the accumulation of amyloid-beta in both early and late stages of AD.¹ Recently, XPro1595 (INmune Bio), a selective, brain penetrant neutralizer, was investigated for safety and pharmacological activity in a 12-week, phase 1b, open-label dose finding study among patients with AD (NCT03943264).²

Findings from the phase 1b trial showed that treatment with XPro1595 improved microstructural changes in the white matter tracts most affected in patients with AD. In a new post-hoc analysis presented at the 2023 Alzheimer’s Association International Conference, July 16-20, in Amsterdam, the Netherlands, similar findings were reported in the gray matter of the same cohort. Above all, findings demonstrated a dose dependent enhancement in gray matter measures in the brain in among patients with AD who were treated with the therapy.³

During the meeting, senior author RJ Tesi, MD, chief executive officer at INmune Bio, sat down in an interview with NeurologyLive® to further discuss research on XPro1595. He talked about how the approach from the phase 1 study in targeting neuroinflammation in the brain differs from conventional methods. He also spoke about the role of microglia in neuroinflammation, and how cells can be influenced to enhance brain health. Additionally, he explained how controlled inflammation contributes to cognitive improvement in individuals with neurodegenerative conditions like AD.

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REFERENCES
1. Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2019;76(7):791-799. doi:10.1001/jamaneurol.2019.0765
2. Pope P, Ridgway GR, Barnum CJ, et al. Cortical microstructural MRI for detection of early target engagement in AD drug trials: post-hoc analysis of exploratory outcomes from a Phase 1b safety study for XPro1595 in AD. Presented at: 2022 Alzheimer’s Association International Conference; July 16 to July 20; Amsterdam, the Netherlands. Abstract 83219.
3. INmune Bio Inc. Announces Novel MRI Biomarker Data Demonstrating Improvement in Gray Matter in Patients with Alzheimer’s Disease. News Release. Published July 11, 2023. Accessed July 26, 2023. https://www.inmunebio.com/news-2/2023/528-muneioncnnouncesoveliomarkerataemonstr20230711