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Gene Therapy: Oral Gene Delivery System For Inflammatory Bowel Disease Works, Study Shows

Date:
May 22, 2008
Source:
Northeastern University
Summary:
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. Now medical scientists 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.

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 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 most recent findings of the four-year project evaluating the efficiency of Nanoparticles-in-Microsphere Oral Systems (NiMOS) oral gene delivery system have just been published.

The article discusses the effectiveness of oral interleukin-10 or IL-10 (anti-inflammatory protein molecules) gene therapy for the treatment of IBD. 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 eight days of oral gene therapy treatment, the animals receiving NiMOS treatment showed body weight gain back to the original four 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.”

The findings discussed in this paper are part of an ongoing, four-year research project funded by a $1.34 million grant by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). The research team also includes as co-investigator, Dr. Akio Ohta, Assistant Professor of Pharmaceutical Sciences at Northeastern and a member of the New England Inflammation and Tissue Protection Institute, and as consultant, Dr. Takeshi Sano, Associate Professor of Radiology and Director of the Center for Molecular Imaging, Diagnosis, and Therapy at Beth Israel Deaconess Medical Center and Harvard Medical School.


Story Source:

The above story is based on materials provided by Northeastern University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Oral IL-10 Gene Delivery in a Microsphere-based Formulation for Local Transfection and Therapeutic Efficacy in Inflammatory Bowel Disease. Gene Therapy, May, 2008. doi:10.1038/gt.2008.67

Cite This Page:

Northeastern University. "Gene Therapy: Oral Gene Delivery System For Inflammatory Bowel Disease Works, Study Shows." ScienceDaily. ScienceDaily, 22 May 2008. <www.sciencedaily.com/releases/2008/05/080520163044.htm>.
Northeastern University. (2008, May 22). Gene Therapy: Oral Gene Delivery System For Inflammatory Bowel Disease Works, Study Shows. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2008/05/080520163044.htm
Northeastern University. "Gene Therapy: Oral Gene Delivery System For Inflammatory Bowel Disease Works, Study Shows." ScienceDaily. www.sciencedaily.com/releases/2008/05/080520163044.htm (accessed April 24, 2014).

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