Eradication of Borrelia Persisters for More Effective Treatment of Persistent Lyme Disease
Abstract
Although the majority of Lyme disease patients can be cured with 2-4 week treatment with doxycycline or amoxicillin, about 10%-20% of the patients continue to suffer persisting symptoms even 6 months after treatment, a condition called post-treatment Lyme disease syndrome (PTLDS). While the cause of PTLDS is unclear, B. burgdorferi persistent infection with persister bacteria not effectively killed by the current Lyme antibiotics may be involved, as shown in animal models and in humans. Thus, a significant drawback of the current Lyme antibiotics such as amoxicillin and doxycycline is that they are not effective against the dormant B. burgdorferi persisters and are ineffective at treating PTLDS. We recently identified a range of promising Food and Drug Administration (FDA)-approved drug candidates used to treat other disease conditions that have higher activity against B. burgdorferi persisters than the current Lyme antibiotics. We found that a drug combination approach, i.e., triple-drug combination with persister active drug daptomycin and current Lyme antibiotics doxycycline and cefuroxime, is able to eradicate different forms of persisters including round bodies and biofilm-like structures, while single drugs or two-drug or even other triple-drug combinations failed to do so. Based on these exciting new findings, we aim to identify highly active drug combination regimens and evaluate the effectiveness of the promising drug combination regimens against Borrelia persisters using the mouse model. Our recent studies on Borrelia persister drugs have generated significant interest in the Lyme disease community, and we anticipate this project will identify highly active drug combinations that eradicate Borrelia persisters not only in vitro but also in the mouse model of Borelia persistence. Since what we propose to evaluate in this project are FDA-approved drugs, drug combinations proven to be effective in the animal studies can be tested in clinical trials immediately without delay. We believe our studies have the potential to provide the much needed more effective treatment for patients who suffer from late manifestations of Lyme disease including PTLDS, which is not helped by the current Lyme antibiotic treatment. Our proposed study may help to improve patient care and quality of life of PTLDS patients by providing a more effective treatment, with the potential to impact on the health and welfare of U.S. Service members, Veterans, their families, and the American public.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710664
Entities
People
- Ying Zhang
Organizations
- Johns Hopkins University
- United States Army