Lead investigator: Scott Dessain, PhD, MD
Bacteria strains that are resistant to antibiotics represent a scourge in developed countries. The growing prevalence of this phenomenon demands new therapeutic approaches. Based on their role in safeguarding cells against antibiotic treatment, biofilms deposited by multidrug-resistant bacteria on the surfaces they colonize offer an attractive target for therapeutic attack. Both patient and nosocomial (hospital-borne) infections contribute to antibiotic-resistant infections of immediate clinical concern. In particular, stubborn infections of patient infusion tubing and other clinical device surfaces are a significant challenge.
LIMR has 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 huMab offers a route for prevention and clearance of drug-resistant bacteria of any strain on clinical tubing or device surfaces.
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.
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.
Each year in the U.S. at least two million people contract an antibiotic-resistant infection, of which at least 23,000 people die, according to the Centers for Disease Control and Prevention. Fighting this threat is a significant public health priority.
Moreover, antibiotic-resistant infection treatment costs in 2018 exceeded $2 billion—doubling since 2002, according to estimates from researchers who studied data from the Medical Expenditure Panel Survey.
Intellectual property position
Pending patent: U.S. provisional patent has been filed.
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):6265-6276.