Novel Therapy Destroys Lyme In Lab

PORTOLA VALLEY, Calif. November 1, 2023 – Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced the development of a potential new drug, HS-291, that targets and destroys Borrelia burgdorferi, the bacterium that causes Lyme disease. Published in the peer-reviewed journal Cell Chemical Biology, this laboratory study represents a novel paradigm shift for anti-microbial treatment research as it is the first to target and inhibit Borrelia burgdorferi HtpG (high-temperature protein G), a specific type of enzyme within the bacteria that causes Lyme disease— a condition affecting nearly 500,000 new patients annually. The research was conducted at Duke University School of Medicine, with collaboration from the University of North Carolina, Tulane University, and Stanford University, and HS-291 is currently in preclinical stage testing at UC Davis.

“As Lyme disease is currently treated with broad-spectrum antibiotics and there are no targeted treatments, we are particularly excited about this discovery, and hopeful that our novel Lyme disease therapeutic HS-291 will specifically destroy the Lyme bacterium without off-target effects or antibiotic resistance,” said Timothy Haystead, PhD, professor of Pharmacology and Cancer Biology, Duke University School of Medicine, Bay Area Lyme Foundation grantee, and co-lead author. “This research has been an incredible opportunity to leverage knowledge from oncology to Lyme disease to design an investigational therapeutic that could one day benefit hundreds of thousands of patients with Lyme.”

This discovery has implications beyond Lyme disease as it demonstrates that using the drug HS-291 to deliver cellular toxins to HtpG, a type of non-essential enzyme that assists the folding or unfolding of large and complex proteins, greatly expands what can be considered druggable within any pathogen and opens a whole new area of infectious disease research.

When activated, HS-291, an inhibitor of HtpG tethered to the photoactive cellular toxin verteporfin, causes discrete protein modifications, which wreaks havoc on the Lyme disease bacterium’s DNA. This impacts multiple processes including nucleoid collapse and cell wall disruptions. A single dose of HS-291, when activated by light, irreversibly damages Borrelia proteins in close proximity of Bb HtpG in vitro.

“Antibiotics used to treat Lyme disease do not always work for all patients, which causes many to suffer for years with extreme symptoms including neurocognitive issues, disabling fatigue and sleep disruption,” said Linda Giampa, executive director of the Bay Area Lyme Foundation. “Bay Area Lyme concentrates on funding innovative research, including projects where knowledge can be deployed from other areas of medicine. We hope that this discovery will inspire others to join us in investing in impactful, translational research to bring relief to patients.”

This research was made possible by a 2020 Bay Area Lyme Foundation grant of more than $2 million to Duke University School of Medicine in honor of Neil Spector, MD, a renowned oncologist who passed away from complications of Lyme disease that had been misdiagnosed for years. He encouraged scientists to take cancer staging techniques and immunotherapy learnings from oncology and apply them to Lyme research. Dr. Spector was the Sandra Coates associate professor in the Duke University Department of Medicine and also served on Bay Area Lyme Foundation’s Scientific Advisory Board.

Haystead and Spector joined forces as Spector sought to leverage his knowledge of oncology to help better understand Lyme disease, and Haystead’s research is focused on the use of chemical biology approaches to define novel drug targets focused on the treatment of hypertension, obesity, cancer, inflammatory and infectious disease.

Bay Area Lyme Foundation also funded University of North Carolina collaborator, Matt Redinbo, PhD’s research on HS-291; his lab’s crystallography work was instrumental in the discovery process.

Bay Area Lyme Foundation’s research grant program was made possible by the support from the Fairbairn Family, the Younger Family Fund, and Project Lyme.