PGC Anti-MRSA

Development Stage

Pre-clinical

Description

The PGC Anti-MRSA product is a PGC-Metal Bridge formulation of a ~30 kDa protein shown to have significant and specific activity against Staphylococci. It kills both MSSA and MRSA and, importantly, is highly effective against biofilms. It has an extremely short serum half-life (>90% reduction in serum levels in one hour) that has limited its clinical utility to date. Formulation with PGC is ideal for an injectable anti-infective compound due to its passive accumulation at the infection site.

Status

PharmaIN has developed several preliminary IV formulations of protein bound to the PGC carrier. In vivo PK testing in a rat model showed increased half-life of formulated protein vs. the unformulated protein, with a >3-fold increase in AUC when loaded at 50% w/w.

In experiments performed with Dr. David Andes at the University of Wisconsin, a neutropenic murine thigh infection model was used with a nosocomial MRSA isolate to investigate in vivo efficacy of the formulation. The thighs of mice were infected with 106.5 to 107.4 CFUs of MRSA. Two hours later, mice were treated with a single IV injection of formulated and unformulated anti-MRSA protein and viable CFUs per thigh were evaluated for up to 24h. Animals were euthanized and the burden of organisms quantified at five time points (0, 2, 6, 12, and 24h).

As shown above, lysostaphin formulated in PGC had a sustained killing effect. Whereas unformulated protein resulted in re-growth of MRSA after only 6h post-treatment, protein formulated with PGC improved killing power and suppressed re-growth for at least 24h post-treatment, resulting in a two log decrease (99% reduction) in bioburden as compared to unformulated protein at 24h. We believe that this very significant increase in efficacy, relative to only a marginal improvement in PK, is due to passive accumulation of the PGC nanocarrier at the infection site.