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.