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Lankenau Institute for Medical Research discovers human antibody that shows promise against Alzheimer’s disease

Lankenau Medical Center May 11, 2015 Research News

(Wynnewood, PA) – An international research team, led by scientists at the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, has discovered a human antibody that shows promise as a treatment for Alzheimer’s disease (AD), the most common form of dementia. The researchers reported their findings in the April 22, 2015 issue of The Journal of Neuroscience.

The new discovery builds on prior research demonstrating that human serum contains antibodies that recognize and neutralize activity of the toxic beta-amyloid proteins implicated in AD. The research team set out to isolate a single human antibody that is highly specific for beta-amyloid aggregates and to assess whether it has protective effects in animal models. They found such an antibody by studying the immune response of a healthy young volunteer.

“This exciting study demonstrates the potential power of the human immune system to make antibodies we can use to treat diseases,” remarked George Prendergast, PhD, President and CEO of LIMR. “After all, the human immune system has evolved to protect us, and the antibodies it makes reflect that critical role. Artificial systems for making antibodies, using rodents or single-celled organisms, have a much harder time replicating such unique and valuable molecules.”

AD is an age-related, progressive, degenerative dementia characterized by the accumulation of beta-amyloid proteins in the brain and subsequent formation of toxic amyloid aggregates (plaques). Beta-amyloid aggregates are thought to play a primary role in AD pathophysiology—disrupting synaptic and cellular functions and ultimately leading to neurodegenerative, cognitive, and neuropsychiatric symptoms.

The research team, led by LIMR scientist Scott Dessain, MD, PhD, analyzed the immune response of a healthy young person and cloned one antibody—called 3H3—that specifically bound to beta-amyloid aggregates. They found that 3H3 not only prevented the formation of toxic aggregates of beta-amyloid protein in vitro, it potently inhibited the toxic effect of these aggregates in a mouse brain model of human AD.

A notable feature of the study was the use of an adeno-associated virus to express a 3H3 antibody fragment in the brains of mice prone to develop beta-amyloid deposition similar to AD. In experiments performed by one of the collaborators, Yona Levites, PhD, the antibody was shown to reduce the load of toxic beta-amyloid in this mouse model of AD. Levites then extended the study to show that 3H3 also reduces deposition of a similar aggregated amyloid protein in a mouse model of familial Danish dementia. These results suggest that the antibody 3H3 may have value as a potential treatment for AD and other amyloid-related diseases in humans.

AD is the most common form of dementia. According to the Alzheimer’s Association, the disease affects 5.3 million Americans and is the sixth-leading cause of deaths in the United States. Current approved treatments address only the symptoms of AD, not the underlying mechanism of the disease.

Until recently, antibodies have failed to show promise as potential treatment for AD in clinical trials. However, in March 2015, Biogen released an interim analysis of data from a Phase 1b trial of aducanumab, which, like 3H3, is an antibody with high affinity for binding toxic beta-amyloid aggregates. The early analysis showed that in patients with AD, aducanumab resulted in a reduction in the levels of amyloid plaques in the brain and significant slowing of cognitive and functional decline, compared to placebo.

Dessain and his LIMR colleagues collaborated with an international research team that included Yona Levites, PhD, and Todd Golde, MD, PhD, of the University of Florida in Gainesville; Brian O’Nuallain, PhD, and Dominic Walsh, PhD, of Brigham and Women’s Hospital in Boston; and Tomas Ondrejcak, PhD, and Michael Rowan, PhD, of Trinity College in Dublin.

The research was supported by the Sharpe-Strumia Research Foundation of Bryn Mawr Hospital, the Edward N. and Della Thome Memorial Foundation, NIH Grant AG18454, and Science Foundation Ireland. Read the full text of the published study.

Levites Y, O’Nuallain B, Puligedda RD, Ondrejcak T, Adekar SP, Chen C, Cruz PE, Rosario AM, Macy S, Mably AJ, Walsh DM, Vidal R, Solomon A, Brown D, Rowan MJ, Golde TE, Dessain SK. A human monoclonal IgG that binds A assemblies and diverse amyloids exhibits anti-amyloid activities in vitro and in vivo. J Neurosci. 2015;35:6265–76.

About Lankenau Institute for Medical Research

Lankenau Institute for Medical Research (LIMR) is a nonprofit biomedical research institute located on the campus of Lankenau Medical Center and is part of Main Line Health. Founded in 1927, LIMR’s mission is to improve human health and well-being. Faculty and staff are devoted to advancing innovative new approaches to formidable medical challenges, including cancer, cardiovascular disease, gastrointestinal disorders and autoimmune diseases, such as diabetes and arthritis. LIMR’s principal investigators conduct basic, preclinical and translational research, using their findings to explore ways to improve disease detection, diagnosis, treatment and prevention. They are committed to extending the boundaries of human health through technology transfer and training of the next generation of scientists and physicians.