Beyond antibiotics: 'PPMOs' offer new approach to bacterial infection, other diseases

In animal studies, one form of PPMO showed significant control of two strains of Acinetobacter, a group of bacteria of global concern that has caused significant mortality among military personnel serving in Middle East combat.

The new PPMOs offer a fundamentally different attack on bacterial infection, researchers say.

They specifically target the underlying genes of a bacterium, whereas conventional antibiotics just disrupt its cellular function and often have broader, unwanted impacts. As they are further developed, PPMOs should offer a completely different and more precise approach to managing bacterial infection, or conceptually almost any disease that has an underlying genetic component.

The findings were published today in the Journal of Infectious Diseases, by researchers from OSU, the University of Texas Southwestern Medical Center, and Sarepta, Inc., a Corvallis, Ore., firm.

"The mechanism that PPMOs use to kill bacteria is revolutionary," said Bruce Geller, a professor of microbiology in the OSU College of Science and lead author on the study. "They can be synthesized to target almost any gene, and in that way avoid the development of antibiotic resistance and the negative impacts sometimes associated with broad-spectrum antibiotics.

"Molecular medicine," Geller said, "is the way of the future."

PPMO stands for a peptide-conjugated phosphorodiamidate morpholino oligomer -- a synthetic analog of DNA or RNA that has the ability to silence the expression of specific genes. Compared to conventional antibiotics, which are often found in nature, PPMOs are completely synthesized in the laboratory with a specific genetic target in mind.

In animal laboratory tests against A. baumannii, one of the most dangerous Acinetobacter strains, PPMOs were far more powerful than some conventional antibiotics like ampicillin, and comparable to the strongest antibiotics available today. They were also effective in cases where the bacteria were resistant to antibiotics.

PPMOs have not yet been tested in humans. However, their basic chemical structure, the PMO, has been extensively tested in humans and found safe. Although the addition of the peptide to the PPMO poses an uncertain risk of toxicity, the potency of PPMOs reduces the risk while greatly improving delivery of the PMOs into bacterial cells, Geller said.

Geller said research is being done with Acinetobacter in part because this pathogen has become a huge global problem, and is often spread in hospitals. It can cause respiratory infection, sepsis, and is a special concern to anyone whose immune system is compromised. Wounds in military battle conditions have led to numerous cases in veterans, and A. baumannii is now resistant to many antibiotics. "Urgent new approaches to therapeutics are needed," the scientists said in their report.

Continued research and eventually human clinical trials will be required before the new compounds are available for health care, the researchers said. This and continued studies have been supported by the National Institutes of Health, the other collaborators and the N.L. Tartar fund.