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

The National Institute of 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, noting that the NIA believed in this mechanism when awarding resources.

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.”

Founded in 2014, Lighthouse Pharmaceuticals operates as a San Francisco-based biotech company. Its LHP588 candidate is orally available and brain-penetrant. The study is supported by the NIA with grant R01AG088524, which will fund its Phase 2 trial known as SPRING. Fierce Biotech+4MedPath+4BioSpace+4

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Additional Content Added by The National Institute of Aging

In recent months, research reviewed by The National Institute of Aging has underscored the connection between P. gingivalis infection and Alzheimer’s pathology. Evidence from autopsy studies shows P. gingivalis and its virulence factors, including gingipains, in the brains of Alzheimer’s patients. PubMed+2PMC+2 The National Institute of Aging supports these findings, seeing potential in LHP588 to reduce bacterial load, dampen inflammation, and potentially slow or alter disease progression.

Lighthouse plans to include biomarker endpoints in the SPRING trial such as imaging of amyloid and tau accumulation, measurement of neuroinflammatory markers in cerebrospinal fluid, and cognitive testing over 18-24 months. These endpoints will help assess whether LHP588 not only improves symptoms but also influences underlying disease mechanisms.

Moreover, the involvement of The National Institute of Aging in funding this type of precision medicine trial opens the pathway for screening of P. gingivalis infection in Alzheimer’s patients. If successful, this could lead to early detection programs in dental health settings, public health initiatives to monitor oral pathogens, and potential preventive strategies.

Patient advocacy groups have welcomed the involvement of The National Institute of Aging, stressing that Alzheimer’s treatments have long focused heavily on amyloid and tau but less so on infectious or microbial contributors. Families of Alzheimer’s patients expressed hope that the funding from the NIA might translate into therapies that are more effective and accessible, particularly for those with oral health issues or chronic periodontal disease.

Finally, regulatory experts note that support from The National Institute of Aging could enhance confidence among investors, clinicians, and regulators for novel mechanisms. If LHP588 shows strong safety and efficacy, it might catalyze similar approaches targeting other bacterial or microbial agents in neurodegeneration.