Muna Therapeutics targets brain resilience with drug designed to enhance neural health by harnessing established protective mechanisms.
Denmark’s Muna Therapeutics has dosed the first participants in a Phase 1 clinical trial of its therapy designed to target early-stage Alzheimer’s disease by enhancing the brain’s innate protective mechanisms. The Copenhagen-based company’s approach focuses on the concept of brain resilience – the ability of the brain to preserve function despite the presence of misfolded protein pathology.
Misfolded proteins are a feature of neurodegenerative diseases like Alzheimer’s, accumulating in the brain and forming toxic aggregates that disrupt cellular processes and spread from cell to cell. However, Muna claims that around one-third of older individuals without dementia exhibit this pathology but retain cognitive performance, suggesting that their resilience mechanisms may be preventing the negative impact of misfolded proteins. Muna’s approach focuses on identifying the cellular and molecular systems that underpin this resilience to guide its target selection and drug development.
The company’s lead compound, MNA-001, is a small-molecule agonist of TREM2 (triggering receptor expressed on myeloid cells 2), a key signaling protein that regulates microglial activity in the brain. Microglia are immune cells that help maintain neural health by clearing misfolded proteins and cellular debris associated with neurodegeneration. Genetic studies suggest that variations in TREM2 can either heighten or reduce Alzheimer’s risk, and Muna’s approach aims to activate the protein to restore microglial balance, enhancing their capacity to protect neurons and maintain cognitive function.
“Our goal is to fundamentally shift the focus in Alzheimer’s disease treatment from clearing pathology to bolstering the brain’s innate protective mechanisms,” said Muna CEO Dr Rita Balice-Gordon.
The company says its preclinical research demonstrated that MNA-001 achieves strong brain exposure following oral dosing and engages TREM2 at nanomolar potency. In mouse models of Alzheimer’s-like pathology, three months of treatment led to a significant reduction in amyloid burden and reprogrammed microglia from a disease-associated state to a homeostatic, protective one.
In addition to evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of MNA-001 in healthy adult and elderly participants, the Phase 1 trial will also measure biomarkers in plasma and cerebrospinal fluid that indicate TREM2 activation and microglial engagement. The trial’s topline data are expected in mid-2026 and are anticipated to offer early insights into how MNA-001 influences biomarkers of resilience and neuroprotection in humans.
“We intend for this to be the first of several innovative approaches to enhance the brain’s resilience to pathological drivers of neurodegeneration,” said the Chair of Muna’s board, Dr Donald Nicholson.
Beyond MNA-001, the company’s pipeline includes early-stage programs focused on microglial and neuronal resilience, including an initiative aimed at Parkinson’s disease and multiple sclerosis targeting Kv1.3, a voltage-gated potassium channel that regulates microglial reactivity and inflammation. Elevated Kv1.3 activity has been linked to neurodegenerative pathology, and preclinical studies suggest that its inhibition can reduce neuroinflammation and protect neurons. Muna’s small-molecule Kv1.3 inhibitors are being optimized for high selectivity, strong brain exposure and oral bioavailability.
Last year, Muna entered a research collaboration with GSK to identify and validate novel targets for Alzheimer’s using its platform. Under the agreement, Muna received an upfront payment of €33.5 million and could earn up to €140 million per target in milestone payments, along with tiered royalties on future product sales.
