Inflammatory bowel disease (IBD) afflicts as many as 10 out of 100,000 people in the United States and currently available treatment options are short-term and invasive with toxic side effects. Northeastern University professor Mansoor Amiji (pictured), and his team are successfully developing a safe and effective, orally administered non-viral gene delivery system that promises a painless treatment option with long-term effects and aims to ultimately replace the frequent injection regimen offered to patients today.
The findings indicate that upon oral administration of NiMOS, transfection and local expression of IL-10 can not only suppress the levels of pro-inflammatory cytokines, but can also increase body weight, restore colon length and weight, and suppress inflammatory tissue response.
“Our findings provide highly encouraging evidence of oral gene delivery for efficient transfection,” Amiji, Professor and Associate Chairman of the Pharmaceutical Sciences Department in Northeastern’s Bouvé College of Health Sciences. “The reality of being able to produce drugs at the site of inflammation promises to eliminate frequent invasive administration of drugs with strong side effects.”
The researchers compared the capacity and efficiency of IL-10-expressing plasmid DNA administered in NiMOS with those encapsulated in gelatin nanoparticles in colitis-induced mice. Over the course of 8 days of oral gene therapy treatment, the animals receiving NiMOS treatment showed body weight gain back to the original 4 days after the loss of more than 10% of the original weight. Amiji and his co-author, Dr. Mayank Bhavsar (a recent graduate from Amiji’s lab) also observed the restoration of colon length and weight in this group of mice, as well as significant decrease in disease activity.
“These results can only be attributed to the increased local levels of IL-10 upon treatment,” added Amiji, who is also the Co-Director of Nanomedicine Education and Research Consortium (NERC) at Northeastern University. “This is evidence that NiMOS treatment is highly effective, therefore promising a clinically translatable option for IBD treatment that offers a very high patient-compliant therapeutic approach.”
Although preclinical studies have been done successfully on delivery of plasmid DNA encoding for IL-10 using viral vectors, the potential toxicity of viruses, especially upon chronic administration poses significant concern.
“Being a non-viral delivery system makes NiMOS a revolutionary form of oral gene therapy,” said Amiji. “Non-viral delivery that provides efficient transfection has the potential for research to be translated into clinical reality, especially for the treatment of chronic diseases such as IBD.”
Illustration: Northeastern University.
Northeastern University Press Release (05/19/08)
Science Daily (05/22/08)
Abstract (Gene Therapy; (04/17/08))