Cholesterol-binding peptide to inhibit pathogen activity

TECHNOLOGY

Treatment of bacterial diseases has become increasingly difficult as the number of

antibiotic-resistant organisms increases and the development of new antibiotics

decreases. According to the CDC, an estimated 2 million people in the US develop

antibiotic infections annually with more than 23,000 deaths at a cost of $21-34

billion/year. Therefore, in addition to preventing infections, tracking resistant

organisms, and more conservative antibiotic use, there is a need for novel

antimicrobial strategies. Cholesterol is a primary component of eukaryotic cell

plasma membranes and therefore plays an essential role in cell membrane structure

and membrane protein function. Many transmembrane proteins bind directly to

cholesterol and/or associate with cholesterol-rich domains such as lipid rafts. The

cholesterol recognition amino acid consensus (CRAC) motif is used by many

pathogens to recognize cholesterol on the host cell membrane as an initial step in

pathogenesis prior to the toxin or virus moving from the aqueous extracellular

environment to hydrophobic membrane environment. Disruption of this recognition

may inhibit bacterial/viral pathogenesis.

 

The use of CRAC peptide (delivered by liposomes) can be used as an initial step in

the prevention of disease transmittance without human cell toxicity. It recognizes the

hydroxyl group of cholesterol with strong, nanomolar affinity without disrupting

membrane packing, binding primarily near the membrane surface. This prevents

internalization of toxins and viral proteins by host cells resulting in inhibition of

toxin activity for up to 65 days without toxicity to normal cells.

 

COMPETITIVE ADVANTAGE

 

 Broad applicability in preventing disease transmittance without removing

    cholesterol from the cell membrane, thereby preventing human cell toxicity

 

 Allows the host defense system to eliminate attenuated bacteria, helping to

                overcome induction of antibiotic resistance

 

 Increases the effectiveness of co-administered antibiotics

 

 Peptide delivery by liposomes increas es drug stability/circulation time,

 

    allowing for higher drug loading and efficient, targeted delivery

 

 May be effective against drug-resistant species

 

OPPORTUNITY

Treatment of bacterial disease is increasingly difficult as the number of antibiotic-

resistant organism’s increases, necessitating the need for novel, broad-spectrum

strategies. In 2012, the global antibacterial drugs market was valued at $43.55 billion

and is expected to grow at a CAGR of 0.3% from 2013 to 2019, to reach an

estimated $45.09 billion in 2019. The increasing prevalence of infectious diseases

and rising demand for effective as well as affordable antibacterial drugs along with

the increase in multi-drug resistant bacterial strains are the major growth drivers for

the antibacterial drugs market. The rise in the elderly population is one of the major

growth factors that will indirectly increase demand for various antibacterial drugs.

 

Lehigh University is looking for a partner for further development and

commercialization of this technology through a license.

 

Tech ID:

081716-01

 

Inventors:

Angela Brown

Edward Lally

Category(s):
Chemical
For Information, Contact:
Thomas Meischeid
Interim Director
Lehigh University
tjm5@lehigh.edu
Inventors:
Angela Brown
Kathleen Boesze-Battaglia
Edward Lally
Keywords: