First Trial of Alzheimer’s Nasal Vaccine to Begin

Brigham and Women’s Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer’s disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial comes after nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the hospital. The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer’s but otherwise generally healthy. They will receive two doses of the vaccine one week apart, the hospital said in a press release. The participants will enroll from the Ann Romney Center. A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness.

The vaccine uses a substance called Protollin, which stimulates the immune system.

Protollin is designed to activate white blood cells found in the lymph nodes on the sides and back of the neck to migrate to the brain and trigger clearance of beta amyloid plaques — one of the hallmarks of AD [Alzheimer’s disease],” the hospital explains. It notes that Protollin has been found to be safe in other vaccines. “The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Weiner in the hospital’s press 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.”

The researchers say they aim to “determine the safety and tolerability of the nasal vaccine” in the trial and observe how Protollin affects participants’ immune response, including how it affects their white blood cells. “The immune system plays a very important role in all neurologic diseases,” Weiner added. “And it’s exciting that after 20 years of preclinical work, we can finally take a key step forward toward clinical translation and conduct this landmark first human trial.”

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,” said Tanuja Chitnis, MD, professor of neurology at Brigham and Women’s Hospital and principal investigator of the trial.

I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical are responsible for developing, manufacturing and commercializing Protollin.

Source: https://www.cbsnews.com/

Regenerative Therapy Reverses Hearing Loss

The biotechnology company Frequency Therapeutics is seeking to reverse hearing lossnot with hearing aids or implants, but with a new kind of regenerative therapy. The company uses small molecules to program progenitor cells, a descendant of stem cells in the inner ear, to create the tiny hair cells that allow us to hearHair cells die off when exposed to loud noises or drugs including certain chemotherapies and antibiotics. Frequency’s drug candidate is designed to be injected into the ear to regenerate these cells within the cochlea. In clinical trials, the company has already improved people’s hearing as measured by tests of speech perception—the ability to understand speech and recognize words.

Speech perception is the No. 1 goal for improving hearing and the No. 1 need we hear from patients,” says Frequency co-founder and Chief Scientific Officer Chris Loose Ph.D.

In Frequency’s first clinical study, the company saw statistically significant improvements in speech perception in some participants after a single injection, with some responses lasting nearly two years. The company has dosed more than 200 patients to date and has seen clinically meaningful improvements in speech perception in three separate clinical studies, with some improvements lasting nearly two years after a single injection. Another study failed to show improvements in hearing compared to the placebo group, but the company attributes that result to flaws in the design of the trial. Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.

The company’s founders, including Loose, MIT Institute Professor Robert Langer, CEO David Lucchino MBA, Senior Vice President Will McLean Ph.D., and Harvard-MIT Health Sciences and Technology affiliate faculty member Jeff Karp, are already gratified to have been able to help people improve their hearing through the clinical trials. They also believe they’re making important contributions toward solving a problem that impacts more than 40 million people in the U.S. and hundreds of millions more around the world.

Hearing is such an important sense; it connects people to their community and cultivates a sense of identity,” says Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential to restore hearing will have enormous impact on society.

Source: https://www.frequencytx.com/
AND
https://neurosciencenews.com/

Nasal Vaccine to prevent Alzheimer’s

Brigham and Women’s Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer’s disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial comes after nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the hospital.

The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer’s but otherwise generally healthy. They will receive two doses of the vaccine one week apart, the hospital said in a press release. The participants will enroll from the Ann Romney Center.

A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness. The vaccine uses a substance called Protollin, which stimulates the immune system. “Protollin is designed to activate white blood cells found in the lymph nodes on the sides and back of the neck to migrate to the brain and trigger clearance of beta amyloid plaques — one of the hallmarks of AD [Alzheimer’s disease],” the hospital explains. It notes that Protollin has been found to be safe in other vaccines.

The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Weiner in the hospital’s press 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.”

The researchers say they aim to “determine the safety and tolerability of the nasal vaccine” in the trial and observe how Protollin affects participants’ immune response, including how it affects their white blood cells.

The immune system plays a very important role in all neurologic diseases,” Weiner added. “And it’s exciting that after 20 years of preclinical work, we can finally take a key step forward toward clinical translation and conduct this landmark first human trial.”

Source: brighamandwomens.org
AND
https://www.cbsnews.com/

Nanoparticle Drug-Delivery To Treat Brain Disorders

In the past few decades, researchers have identified biological pathways leading to neurodegenerative diseases and developed promising molecular agents to target them. However, the translation of these findings into clinically approved treatments has progressed at a much slower rate, in part because of the challenges scientists face in delivering therapeutics across the blood-brain barrier (BBB) and into the brain.

To facilitate successful delivery of therapeutic agents to the brain, a team of bioengineers, physicians, and collaborators at Brigham and Women’s Hospital and Boston Children’s Hospital created a nanoparticle platform, which can facilitate therapeutically effective delivery of encapsulated agents in mice with a physically breached or intact BBB. In a mouse model of traumatic brain injury (TBI), they observed that the delivery system showed three times more accumulation in brain than conventional methods of delivery and was therapeutically effective as well, which could open possibilities for the treatment of numerous neurological disorders.

It’s very difficult to get both small and large molecule therapeutic agents delivered across the BBB,” said corresponding author Nitin Joshi, PhD, an associate bioengineer at the Center for Nanomedicine in the Brigham’s Department of Anesthesiology, Perioperative and Pain Medicine. “Our solution was to encapsulate therapeutic agents into biocompatible nanoparticles with precisely engineered surface properties that would enable their therapeutically effective transport into the brain, independent of the state of the BBB.”

The technology could enable physicians to treat secondary injuries associated with TBI that can lead to Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, which can develop during ensuing months and years once the BBB has healed.

To be able to deliver agents across the BBB in the absence of inflammation has been somewhat of a holy grail in the field,” said co-senior author Jeff Karp, PhD, of the Brigham’s Department of Anesthesiology, Perioperative and Pain Medicine. “Our radically simple approach is applicable to many neurological disorders where delivery of therapeutic agents to the brain is desired.”

Findings were published in Science Advances.

https://www.eurekalert.org/