Shedding light on the mysteries of brain disease
May 06, 2015 — Ottawa, Ontario
Breaking down brain barriers one molecule at a time
The inner workings of the human brain hold mysteries that continue to challenge medical researchers and scientists around the world. One such mystery is determining how to delay the progression of brain diseases such as Alzheimer’s, Multiple Sclerosis (MS) and Parkinson’s. Now an important Canadian research breakthrough may have found the key to slowing their spread.
For the past six years, scientists, medical specialists and researchers with the National Research Council’s (NRC) Therapeutics Beyond Brain Barriers (TBBB) program have been developing carrier molecules that enable disease-fighting molecules to penetrate the blood-brain barrier. Once across this barrier, these carrier molecules can release medicinal therapeutics directly into the central nervous system (CNS) where they can have an immediate therapeutic impact.
Danica Stanimirovic, Director of NRC's Translational Bioscience Department, explains that she and her team have developed a series of small antibodies that can infiltrate this barrier by exploiting the same mechanism that allows nutrients to enter the brain. Acting as a Trojan horse, the antibodies trick the blood-brain barrier into allowing their entry and shuttle in therapeutic molecules at the same time.
Getting meds to where they matter
To determine whether the carrier molecules would deliver therapeutics to their intended disease targets, various configurations of the carriers coupled to therapeutic molecules had to be engineered and rigorously tested. This led to a collaboration with Graham Farrington, Director of the Antibody Discovery Group at Biogen, a biotechnology company with a long history of developing MS therapeutics and bringing new therapies to market. "We were excited to learn that NRC had discovered new carrier molecules," says Farrington. "Their groundbreaking work complements Biogen’s focus on identifying antibodies that can have a therapeutic impact on brain diseases."
Using NRC’s technology, Biogen conducted a number of tests to assess the behaviour and effects of NRC’s carrier molecule once coupled to different Biogen antibodies. The animal trials, which involved a non-invasive procedure of administering the antibodies intravenously into rats and then analyzing the results, showed that the carrier-antibody fusion molecules do indeed have a highly potent therapeutic effect on brain diseases. "This was a critical step in validating the efficacy of these antibodies and setting the stage for clinical trials," adds Farrington.
Both Farrington and Stanimirovic anticipate that the clinical trials for the blood-brain barrier-crossing antibodies could take up to 10 years, but that their research could help to unravel some of the biochemical mysteries that scientists everywhere are trying to understand today.
Moving beyond the barrier
Biologics have become the fastest-growing segment of the pharmaceutical market and there is enormous potential to expand their application to the treatment of brain diseases. "We work closely with Canadian and international companies, medical specialists and other partners to ensure that our solutions get out of the lab and into real life—to industrial sectors, healthcare systems, corporations and the public," says Stanimirovic.
Farrington further adds that "the NRC-Biogen relationship has been a mutually successful handshake with complementary capabilities on each side." Both teams agree that this work will lead to the creation of more therapeutics for both those suffering from brain diseases and for the aging population—conditions that place a heavy burden on not only the patients, but also on families and healthcare systems.
"The ability to customize and engineer this solution for multiple applications gives it global appeal to companies that develop medications for different neurological diseases" says Stanimirovic. With its ongoing research in the field, NRC is well-positioned to break down brain barriers and augment the flow of new brain medicines to clinical trials, thus helping to make treatments available to the public more quickly. And that is what really matters.
- Therapeutics Beyond Brain Barriers program
- A novel platform for engineering blood-brain barrier-crossing bispecific biologics
(Journal of the Federation of American Societies for Experimental Biology)
- Parkinson Society Canada
- Multiple Sclerosis Society of Canada
- Alzheimer Society Canada
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