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Tufts Medical Center lab finds gene therapy can stop harmful antibody production.

07/20/2016

July 18, 2016 (BOSTON) – Tufts Medical Center researchers have found a new way to block harmful antibody production by human plasma cells. The results of this gene silencing approach were reported in a paper, “siRNA targeting the κ light chain constant region: preclinical testing of an approach to nonfibrillar and fibrillar light chain deposition diseases” published in the July 7, 2016 issue of the journal Gene Therapy.

Patients who suffer from diseases such as systemic light-chain amyloidosis, light chain deposition disease and antibody-mediated transplant organ rejection, produce an excessive number of antibodies, which can cause grave damage to the heart and kidneys. Currently, relatively toxic and minimally effective chemotherapy is the only treatment available for these patients. Recognizing a clear need for new therapeutics, the Tufts MC researchers applied the recently developed RNA inhibition technology to show that the use of siRNA for specific types of genes turns off their antibody overproduction and holds promise as a therapy for these light-chain diseases. 

“The use of light chain gene knockdown approaches can revolutionize the treatment of antibody and light-chain mediated diseases,” said Raymond Comenzo, MD, Founding Director of the John Conant Davis Myeloma and Amyloid Program and Director of the Blood Bank and Stem Cell Processing Laboratory at Tufts Medical Center. “This gives patients a targeted therapy option when other treatments fail.”

The study completes the work initially described in an earlier paper, “One siRNA pool targeting the λ constant region stops λ light-chain production and causes terminal endoplasmic reticulum stress,” which appeared in the May 29, 2014 issue of the journal Blood, showing that single sets of small interfering ribonucleic acids (siRNA) can shut off the production of antibodies by targeting constant regions of certain light-chain genes. siRNA works by causing the elimination of messenger RNA for specific proteins, resulting in marked reductions in protein production by cells.

“Our research shows that the knockdown of light chain gene and protein expression is an effective therapy in mice,” said Xun Ma, MD, PhD, DMD, Hematology/Oncology Senior Research Specialist at Tufts Medical Center, and the lead researcher on the Gene Therapy paper. “In the lab, knockdown can cause cell death in human plasma cells making whole antibodies, because without the light chain, the heavy chain part of the antibody gets stuck inside the cells like uncollected garbage and causes terminal cell stress.” 

Dr. Ma presented the findings to an audience of more than 550 experts from around the world in the plenary session at the XVth International Symposium on Amyloidosis in Uppsala, Sweden on July 3, 2016. 

For additional information, please contact the Tufts Medical Center Technology Transfer Office (techtransfer.tufts.edu), reference TMC-534. 

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About Tufts Medical Center and Floating Hospital for Children

Tufts Medical Center is an exceptional, not-for-profit, 415-bed academic medical center that is home to both a full-service hospital for adults and Floating Hospital for Children. Conveniently located in downtown Boston, the Medical Center is the principal teaching hospital for Tufts University School of Medicine. Floating Hospital for Children is the full-service children's hospital of Tufts Medical Center and the principal pediatric teaching hospital of Tufts University School of Medicine. Tufts Medical Center is affiliated with the New England Quality Care Alliance, a network of more than 1,800 physicians throughout Eastern Massachusetts. For more information, please visit www.tuftsmedicalcenter.org.

Media Contact: Jeremy Lechan

(617) 636-0104

jlechan@tuftsmedicalcenter.org