NIA gives Lighthouse $49 million for a study on Alzheimer’s disease linked to bacteria

The National Institute on Aging (NIA), part of the National Institutes of Health, has awarded nearly $50 million to Lighthouse Pharmaceuticals to support its efforts in developing new treatments for Alzheimer’s disease. The funding will accelerate a phase 2 clinical trial of Lighthouse’s brain-penetrant lysine-gingipain (Kgp) inhibitor, LHP588, a potential therapy targeting bacterial infection associated with cognitive decline.

The San Francisco-based biotech will recruit 300 patients with mild to moderate Alzheimer’s disease who also have a Porphyromonas gingivalis infection. P. gingivalis is best known as the bacterium responsible for chronic periodontitis, but it has also been linked to systemic inflammation and neurodegeneration. Recruitment began in February at Northwest Clinical Research Center in Bellevue, Washington, and Lighthouse plans to expand to additional trial sites.

LHP588 follows the company’s first-generation Kgp inhibitor, atuzaginstat, which in earlier trials was associated with a 57% reduction in cognitive decline in patients with Alzheimer’s disease and P. gingivalis infection. According to Lighthouse, targeting lysine-gingipain may directly address neuroinflammation and microbial pathogenesis in Alzheimer’s disease.

Casey Lynch, CEO of Lighthouse, said the NIH support highlights growing recognition of the potential connection between bacterial infection and Alzheimer’s progression. “This funding is a strong validation of our approach to gingipain inhibition as a novel treatment strategy for Alzheimer’s disease,” she said.

Recent advances in Alzheimer’s treatment have largely focused on monoclonal antibodies targeting amyloid-beta plaques, such as Eisai and Biogen’s Leqembi, which became the first FDA-approved therapy in this category. However, an increasing body of research suggests that microbes, including bacteria and viruses, may play a role in neurodegenerative disease. This has opened the door for alternative therapeutic approaches such as Lighthouse’s lysine-gingipain inhibitor.

“This grant makes possible an aggressive clinical trial of a completely new mechanism of action in Alzheimer’s disease,” said Marwan Sabbagh, chair of Lighthouse’s clinical advisory board. “Direct lysine-gingipain inhibition by LHP588 provides a targeted strategy to interrupt the inflammatory cascade believed to drive disease progression in Alzheimer’s patients with P. gingivalis.”