05:00 ETMuna Therapeutics Announces Nature Medicine Publication Validating Microglial State Transitions as Key Drivers of Alzheimer's

Study leveraging Muna's MiND-MAP platform identifies critical tipping point in microglial response to amyloid and tau pathology Findings validate Muna's differentiated strategy targeting TREM2 signaling to boost neuroprotection , /PRNewswire/ -- Muna Therapeutics, a clinical-stage biotechnology company pioneering a new era of drug discovery for neurodegenerative diseases, today announced the publication of a seminal study in Nature Medicine: "Human microglial transitions at the Aβ–Tau inflection point associate with divergent pathways to dementia and resilience." The research, conducted in collaboration with leading institutions across Belgium, the Netherlands, and the United Kingdom, utilized Muna's proprietary MiND-MAP platform to explore why some individuals remain cognitively resilient despite significant brain pathology. Using spatial transcriptomics and single-cell approaches, the team mapped Alzheimer's disease at an unprecedented resolution, revealing that the disease is driven not just by the accumulation of amyloid and tau, but by how microglia, the brain's immune cells, respond to these changes. A central finding of the study is the identification of a critical "tipping point" where microglia shift from an early, potentially protective inflammatory state to a phenotype prominent in later Alzheimer's disease associated with tau pathology and neurodegeneration. Notably, this early protective response is enriched for TREM2-related signaling, a pathway already genetically linked to Alzheimer's risk and the primary target of Muna's Phase 1 clinical candidate, MNA-001, a novel potent, selective and orally administered small molecule. "These findings suggest that the transition from amyloid to tau is not an inevitable outcome, but a dynamic process that is potentially modifiable," said Niels Plath, Ph.D., Chief Scientific Officer of Muna. "By mapping distinct brain environments, we have identified divergent mechanisms of resilience in human brain. This validates our focus on targeting specific microglial transitions to extend cognitive health rather than simply focusing on plaque removal in the context of Alzheimer's disease." The study observed that cognitively intact individuals, including centenarians, appear to maintain brain health either by avoiding harmful microglial transitions or by uncoupling microglial activation from tau accumulation. This insight supports Muna's focus on identifying therapeutic targets capable of enhancing the brain's innate protective mechanisms to develop the next wave of disease-modifying medicines for Alzheimer's disease and other neurodegenerative disorders. "This publication in Nature Medicine underscores the power of our MiND-MAP platform to understand the complex cellular programs driving Alzheimer's," said Rita Balice-Gordon, Ph.D., Chief Executive Officer of Muna. "It reinforces our strategy to bolster the brain's natural defense mechanisms by recalibrating microglial activity through TREM2 agonism. As we advance MNA-001 through Phase 1 clinical testing, these data provide a high-resolution roadmap for interrupting the damaging feedback loops of neuroinflammation to preserve cognition and provide hope for future Alzheimer's treatments." About Muna Therapeutics Muna Therapeutics is pioneering a new era of drug discovery for neurodegenerative diseases by focusing on enhancing resilience to the effects of misfolded protein pathology to protect brain functions like cognition. Muna's all-in-human discovery engine identifies new therapeutic targets that can enhance the brain's innate protective mechanisms. Muna—which means 'to remember' in Old Norse—is developing a portfolio of therapeutics to slow or stop devastating diseases like Alzheimer's and other neurodegenerative disorders. For more information, visit www.munatherapeutics.com. Media Contact: Peg Rusconi Deerfield Group [email protected] SOURCE Muna Therapeutics