Gene Therapy (a Nature pub­li­ca­tion) paper dis­cusses effec­tive oral gene therapy method to treat IBD

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 were pub­lished in the May issue of Gene Therapy, a Nature publication.

The article, titled “Oral IL-​​10 Gene Delivery in a Microsphere-​​based For­mu­la­tion for Local Trans­fec­tion and Ther­a­peutic Effi­cacy in Inflam­ma­tory Bowel Dis­ease” 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 Asso­ci­at­e­Chairman 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.

For more infor­ma­tion, please con­tact Renata Nyul at 617–373-7424 or at r.​nyul@​neu.​edu.

About North­eastern

Founded in 1898, North­eastern Uni­ver­sity is a pri­vate research uni­ver­sity located in the heart of Boston. North­eastern is a leader in inter­dis­ci­pli­nary research, urban engage­ment, and the inte­gra­tion of class­room learning with real-​​world expe­ri­ence. The university’s dis­tinc­tive coop­er­a­tive edu­ca­tion pro­gram, where stu­dents alter­nate semes­ters of full-​​time study with semes­ters of paid work in fields rel­e­vant to their pro­fes­sional inter­ests and major, is one of the largest and most inno­v­a­tive in the world. The Uni­ver­sity offers a com­pre­hen­sive range of under­grad­uate and grad­uate pro­grams leading to degrees through the doc­torate in six under­grad­uate col­leges, eight grad­uate schools, and two part-​​time divi­sions. For more infor­ma­tion, please visit www​.north​eastern​.edu.