Anti-amyloidantibodies: clearing drug-resistant bacteria by targeting the Curli amyloid

Lead investigator: Scott Dessain, PhD, MD

Unmet need

Bacteria strains that are resistant to antibiotics represent a scourge in developed countries, the growing prevalence of which demands new approaches to combat. Biofilms deposited by multidrug-resistant bacteria on the surfaces they colonize offer an attractive target for therapeutic attack, based on their role in safeguarding cells against antibiotic treatment.

Patient and noscomial (hospital-borne) infections both contribute to antibiotic-resistant infections of immediate clinical concern. In particular, stubborn infections of patient infusion tubing and other clinical device surfaces are a primary challenge.

Opportunity

LIMR generated a unique, patient-derived, human monoclonal antibody (huMab) that recognizes a universal structural feature present in all amyloid proteins in nature. In the bacterial kingdom, the amyloid protein Curli is a vital component of the pathogenic biofilm that enforces bacterial drug resistance. LIMR’s huMab dissolves Curli-containing biofilms deposited on patient infusion tubing by drug-resistant bacteria. This finding offers a route for prevention and clearance of drug-resistant bacteria of any strain on clinical tubing or device surfaces.

Unique attributes

The LIMR huMab binds a structural feature common to all amyloids in nature. This structural epitope is not readily accessed, and the huMab represents a rare antibody cloned from a patient. The huMab not only recognizes this common structure but also breaks up amyloid structures.

Clinical applications

The huMab offers uses to clear drug-resistant bacteria by dissolving pathogenic biofilms.

Stage of development

The LIMR huMab has been cloned, and human hybridomas are stored. IgG gene sequences were determined to enable expression in any expression system. Preclinical proof of concept for biofilm clearance has been obtained in collaboration with co-inventors at Temple University.

Intellectual property

Pending patent: U.S. provisional patent has been filed.

Collaboration opportunity

Develop a product to clear drug-resistant bacteria from clinical tubing or other clinical devices.

Relevant publications

• Levites Y, O’Nuallain B, Puligedda RD, Ondrejcak T, Adekar SP, Chen C, Cruz PE, Rosario AM, Macy S, Mably AJ, Walsh DM, Vidal R, Solomon A, Brown D, Rowan MJ, Golde TE, Dessain SK (2015). A human monoclonal IgG that binds aß assemblies and diverse amyloids exhibits anti-amyloid activities in vitro and in vivo. J. Neurosci. 35(16):6265-76.
• Tursi SA, Puligedda RD, Szabo P, Nicastro LK, Miller AL, Qiu C, Gallucci S, Relkin NR, Buttaro BA, Dessain SK, Tükel Ç. (2020) Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli. Nat Commun. 2020 Feb 21;11(1):1007.

Contacts

Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]

L2C Partners contact: Merle Gilmore, 610.662.0940, [email protected]