Bay Area Lyme Foundation ELA Winner Uses Metabolic Modeling to Predict 77 Unique Drug Targets in Lyme Disease Bacterium

Peter Gwynne, PhD

FOR IMMEDIATE RELEASE

 

Bay Area Lyme Foundation ELA Winner Uses Metabolic Modeling to Predict 77 Unique Drug Targets in Lyme Disease Bacterium

Results will help inform future research and development of new Lyme disease therapeutics

PORTOLA VALLEY, Calif., October 19, 2023—Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced the findings of a study identifying new essential gene and enzyme drug targets in Lyme disease bacterium, which resulted, in-part, from a grant provided to Peter Gwynne, one of Bay Area Lyme Foundation’s 2022 Emerging Leader Award (ELA) winners. Published in the peer-reviewed journal mSystems, the study uses the most comprehensive metabolic modeling to date to predict 77 unique drug targets in Borrelia burgdorferi, the bacterium that causes Lyme disease—a condition affecting nearly 500,000 new patients annually.

“Lyme disease is often treated using long courses of antibiotics, which can cause side effects for patients and risks the evolution of antimicrobial resistance. Our research supplies the blueprint and scaffolding to build better Lyme disease therapeutics that do not have off-target effects for patients,” said Peter Gwynne, PhD, lead author on the study, research assistant professor at Tufts University School of Medicine, and Emerging Leader Award winner of the Bay Area Lyme Foundation. “Many of the 77 genes and enzymes predicted as essential represent candidate targets for the development of novel antiborrelial drug development.”

Current clinical guidelines recommend treatment of Lyme borreliosis with broad-spectrum antibiotics, which can pose risks to the patient’s microbiome. The bacterium that causes Lyme disease is extremely host-dependent, with a small genome and limited metabolism—making it an excellent candidate for the development of targeted, narrow-spectrum antimicrobials.

In the study, the researchers used in silico genome-scale metabolic computer modeling to construct a map of B. burgdorferi metabolism. This map was used to predict essential genes and enzymes that can be used as drug targets. Gwynne and the Tufts University School of Medicine research team validated these targets by repurposing existing drugs that kill B. burgdorferi in culture. While these drugs are not viable treatment options themselves, they provide a blueprint for future novel drug development.

Bay Area Lyme Foundation Researcher Validates New Approach to Overcome Challenges of Lyme Disease Diagnosis in the Lab

Artem Rogovskyy, PhD, DVM, receiving the ELA award at LymeAid

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Bay Area Lyme Foundation Researcher Validates New Approach to Overcome Challenges of Lyme Disease Diagnosis in the Lab

Using samples from the Lyme Disease Biobank, Raman spectroscopy is identified as a potentially more sensitive test for diagnosing Lyme disease

Portola Valley, CA, February 9, 2023 — Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced results of a laboratory study published in the peer-reviewed journal Frontiers in Cellular and Infection Microbiology that identifies Raman spectroscopy as a promising diagnostic approach for Lyme disease, a condition that affects nearly 500,000 new patients annually. Conducted by one of Bay Area Lyme Foundation’s Emerging Leader Award winners, Artem Rogovskyy, PhD, DVM, along with researchers from Texas A&M University, the study identified Borrelia infection with 88% accuracy, 85% sensitivity, and 90% specificity using Raman spectroscopy, a light-based test commonly used in chemistry labs, to evaluate human blood samples provided by Bay Area Lyme Foundation’s Lyme Disease Biobank. 

“By identifying a unique spectrum fingerprint to detect Lyme borreliosis faster, Raman spectroscopy has the potential to diagnose the disease earlier,” said Dr. Rogovskyy, associate professor of Veterinary Pathobiology at the School of Veterinary Medicine and Biomedical Sciences at Texas A&M University. “We hope that developing an effective, robust, and rapid diagnostic test will help overcome current challenges in Lyme disease diagnosis.”

The study aims to address the immediate need for more sensitive diagnostics in Lyme disease as the current gold standard diagnostic has been shown to be insensitive in up to 60% of early-stage patients and up to 30% of late-stage patients.

“The lack of an accurate diagnostic test is not only a challenge for clinicians trying to properly diagnose and treat patients, but also makes clinical trials for new treatments difficult,” said Linda Giampa, executive director, Bay Area Lyme Foundation. “Our hope is that new approaches like this one will allow for early detection and treatment of all patients with Lyme disease.” 

Nanotrap® Urine Test for Lyme Borreliosis

– Wendy Adams, Research Grant Director, Bay Area Lyme Foundation

 

Bay Area Lyme has a goal to leverage the entrepreneurial spirit and innovation of Silicon Valley in order to catalyze novel projects around the country. Our belief is that the application of cutting-edge technologies will have a dramatic impact on making Lyme disease easy to diagnose and simple to cure. We collaborate with world-class scientists focused on Lyme projects which leverage knowledge from other fields of medicine and research. We also prioritize engagement with the investment and biotech communities so that breakthroughs in the laboratory can be translated more quickly to patients. Since our inception, our scientific research funding priorities have been focused on supporting diagnostic and therapeutic projects.

It is impossible to cure Lyme disease in every case without understanding how to diagnose it accurately. There are many reasons for this disease being difficult to identify—ticks are tiny, the EM skin rash is often misdiagnosed and symptoms overlap with other acute diseases like influenza. Most importantly, the widely used two tier diagnostic testing required for Lyme disease is currently the ELISA and Western Blot, which only detects the immune response (indirect detection) and not the pathogen itself. Because it can take at least 2-4 weeks for the body to generate antibodies, these tests have been shown to miss up to 70% of acute Lyme cases. These tests also do not detect other related Borrelia species, such as Borrelia miyamotoi), and cannot determine when the infection is eradicated.