Following its recent success (and drug approvals) over the last decade fighting cancer, immunotherapy is now hoping to take on Alzheimer’s.
Researchers at Brigham and Women’s Hospital in Boston announced the launch of a new human clinical trial that will measure the effectiveness of an immunotherapy drug on the complex neurologic disorder.
The trial will measure the impact of a drug called Protollin, which the hospital calls a “nasal vaccine” they hope will stimulate the body’s own immune reaction to fight the disease—specifically by targeting beta amyloid plaques. These plaques are formed when protein pieces join together and gradually build up, which are believed to disrupt the signaling of cells at the synapses and also possibly trigger the immune system to attack the inflammation.
The drug being tested – created by pharmaceutical company I-Mab Biopharma along with Jiangsu Nhwa Pharmaceutical – is delivered in a spray given inside the nostril to help it more easily reach the brain and activate the body’s immune system. The phase 1 trial will start small with just 16 patients between the ages of 60 and 85 already diagnosed with early Alzheimer’s. In addition to measuring the safety of the drug, researchers will also look at the immune responses of the participants.
“The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Howard Weiner, MD, research lead and co-director of the Ann Romney Center for Neurologic Diseases at the Brigham, in a release. “Over the last two decades, we’ve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimer’s, and it could also be given early to help prevent Alzheimer’s in people at risk.”
Cautiously optimistic?
Alzheimer’s is currently the sixth leading cause of death (and possibly as high as third) in the United States and the most common cause of dementia in older adults. As a progressive brain disorder that slowly annihilates memory and cognitive skills, it’s also currently irreversible and notoriously difficult to treat—one of the reasons many physicians are waiting for more data before weighing in.
“The idea is intriguing and it’s a new way of attacking a very old problem that has been very resistant to effective treatment,” said Andrew Duxbury, MD, professor of clinical geriatrics at the University of Alabama Birmingham. “I have been around long enough to see lots of potential Alzheimer’s therapies based in sound science that simply don’t work in an environment as complex as the human brain, so I am not sure if I should be optimistic or not about this announcement. These first trials are small, carefully monitored and hopefully we will get some encouraging data allowing the researchers to proceed.”
Several existing medications are currently used to treat Alzheimer’s—some to help patients maintain mental function, some to help manage behavioral symptoms, and others to treat the root disease process.
‘A whole new avenue’
Weiner’s work started first in mice with Alzheimer’s, where he found that by giving them multiple sclerosis, the disease activated the immune system of the mice and destroyed the plaque in the brain from the Alzheimer’s.
“You can’t treat Alzheimer’s by giving people MS,” Weiner told the Boston Business Journal. “So, we began to investigate the mechanisms. I discovered the immune system was being activated and cells were going into the brain, clearing the amyloid, and treating the disease. The question was, is there a way to do that that had no side effects and also that could be used in people?”
That led him to Protollin, which triggers the immune system in a similar way—and now his research will continue with human patients in the newly launched trial. While the work is still in the early stages, the team is excited at the potential.
“For 20 years, there has been growing evidence that the immune system plays a key role in eliminating beta amyloid,” said Tanuja Chitnis, MD, principal investigator of the trial. “This vaccine harnesses a novel arm of the immune system to treat AD. Research in this area has paved the way for us to pursue a whole new avenue for potentially treating not only AD but also other neurodegenerative diseases.”
