Novel treatments for Alzheimer's that eliminate harmful proteins from the brain have rekindled interest in vaccines as a means of treating the memory-robbing illness, possibly providing a less expensive and simpler choice for millions of individuals, according to interviews with ten scientists and business executives.
A survey of the U.S. government's ClinicalTrials.gov database revealed that clinical trials for at least seven Alzheimer's vaccines, which aim to use the immune system to rid the brain of the disease-related proteins tau or beta amyloid, are either ongoing or have been completed. There will be more soon.
The resurgence of interest in Alzheimer's vaccinations comes after a prior attempt, which showed promise more than 20 years ago but was shelved after 6% of study participants experienced meningoencephalitis, a potentially fatal inflammation of the brain.
Then, taking a safer approach, researchers injected highly focused artificial antibodies into patients, avoiding the body's defences.
Such medicines as the recently approved Leqembi by Eisai and Biogen and donanemab by Eli Lilly, which is currently undergoing U.S. regulatory assessment, solidified the idea that treating Alzheimer's in its early stages requires cutting out amyloid. Years of setbacks that led many specialists to doubt the amyloid theory were followed by that triumph.
Scientists at Vaxxinity, AC Immune, and Prothena, among others, think they have a better idea of what went wrong with the original vaccine and are studying vaccines that they hope would stimulate the immune system without inducing undue inflammation. The first two vaccinations have been granted fast-track designation by the US Food and Drug Administration, which should expedite the evaluation process.
Researchers studying Alzheimer's at Mass General Brigham in Boston, including Dr. Reisa Sperling, believe vaccines will be crucial in the fight against Alzheimer's. "I'm convinced that's the direction we should go."
Sperling is heading a study including individuals with Alzheimer's proteins in their brains who are cognitively normal. For her next trial, she is thinking about vaccinations for asymptomatic individuals who have blood levels of Alzheimer's proteins, but not enough to show up on brain scans.
The development of Alzheimer's vaccines is still in its infancy, and extensive, multi-year trials will be necessary to demonstrate their efficacy.
Nonetheless, a vaccination administered twice a year or every three months might provide a break from the costly twice-monthly infusions required for Leqembi, hence increasing accessibility for the estimated 39 million Alzheimer's patients worldwide.
"They could be worldwide, and not that expensive," said Dr. Walter Koroshetz, director of the neurological disorders division of U.S. National Institutes of Health.
Vaxxinity is arguably the most advanced, having finished a modest Phase 2 trial for its vaccine, UB-311. Leqembi's accomplishment, according to Chief Executive Mei Mei Hu, confirmed a long-questioned theory.
"What we know is that if we knock out certain bad forms of amyloid, we will see an effect in clinical outcomes, and that's amazing," she said of Leqembi's ability to slow cognitive decline.
Data from the 43 volunteers in Taiwan who took part in Vaxxinity's Phase 2a trial, which was released in August, demonstrated that the vaccination was safe and tolerated after 78 weeks and that nearly all of the subjects developed an antibody response. Brain enlargement was not observed in any patients; however, brain haemorrhage, a typical side effect of the infused therapies, occurred in 14% (6) of the cases.
Though Hu said the environment for the last few years as "quite frigid," Vaxxinity has been looking for a partner to assist fund a larger, confirmatory experiment. "The gates have opened with (Leqembi's) approval, and there's a lot more investment and enthusiasm."
The initial Alzheimer's vaccine showed promise, but it also caused the immune system's T-cells—which are solely meant to kill diseased cells—to react erratically.
The majority of the more recent vaccinations target B cells, which are immunological cells that generate antibodies.
The vaccination from AC Immune only stimulates B cells, according to University of Southern California researcher Dr. Michael Rafii.
Meningoencephalitis was not brought on by the AC vaccine in a Phase 1 trial headed by Rafii; rather, a small percentage of subjects experienced an immunological reaction. A modified version is presently being tested by the business.
The CEO of AC immunological, Andrea Pfiefer, hypothesised that the absence of brain haemorrhage or swelling observed with monoclonal antibodies like Leqembi, which peaks after each infusion, may be explained by the prolonged immunological response to the vaccination in certain patients. In 2024, more data is anticipated in the first half.
Additionally, Johnson & Johnson and AC are working together to develop a vaccination that specifically targets tau, a harmful protein linked to Alzheimer's disease and brain cell death.
In an effort to prevent Alzheimer's disease, Prothena, a business that was split out from the original vaccine's co-developer ten years ago, plans to start a vaccine trial for that vaccine next year. The vaccine targets both tau and amyloid beta.
Additionally, Prothena is in Phase 1 studies for an anti-amyloid antibody and has a licence to use an anti-tau antibody from Bristol Myers Squibb.
CEO of Prothena Gene Kinney stated that a substantial amount of mature antibodies are produced by the company's vaccination. Such vaccines, which are normally administered to older people with weakened immune systems, depend on eliciting a robust immunological response, he said.
For those with pre-symptomatic Alzheimer's, he believes immunisations are the best option. "Your goal should be to stop the illness from ever developing in the first place."
(Source:www.bioethics.com)
A survey of the U.S. government's ClinicalTrials.gov database revealed that clinical trials for at least seven Alzheimer's vaccines, which aim to use the immune system to rid the brain of the disease-related proteins tau or beta amyloid, are either ongoing or have been completed. There will be more soon.
The resurgence of interest in Alzheimer's vaccinations comes after a prior attempt, which showed promise more than 20 years ago but was shelved after 6% of study participants experienced meningoencephalitis, a potentially fatal inflammation of the brain.
Then, taking a safer approach, researchers injected highly focused artificial antibodies into patients, avoiding the body's defences.
Such medicines as the recently approved Leqembi by Eisai and Biogen and donanemab by Eli Lilly, which is currently undergoing U.S. regulatory assessment, solidified the idea that treating Alzheimer's in its early stages requires cutting out amyloid. Years of setbacks that led many specialists to doubt the amyloid theory were followed by that triumph.
Scientists at Vaxxinity, AC Immune, and Prothena, among others, think they have a better idea of what went wrong with the original vaccine and are studying vaccines that they hope would stimulate the immune system without inducing undue inflammation. The first two vaccinations have been granted fast-track designation by the US Food and Drug Administration, which should expedite the evaluation process.
Researchers studying Alzheimer's at Mass General Brigham in Boston, including Dr. Reisa Sperling, believe vaccines will be crucial in the fight against Alzheimer's. "I'm convinced that's the direction we should go."
Sperling is heading a study including individuals with Alzheimer's proteins in their brains who are cognitively normal. For her next trial, she is thinking about vaccinations for asymptomatic individuals who have blood levels of Alzheimer's proteins, but not enough to show up on brain scans.
The development of Alzheimer's vaccines is still in its infancy, and extensive, multi-year trials will be necessary to demonstrate their efficacy.
Nonetheless, a vaccination administered twice a year or every three months might provide a break from the costly twice-monthly infusions required for Leqembi, hence increasing accessibility for the estimated 39 million Alzheimer's patients worldwide.
"They could be worldwide, and not that expensive," said Dr. Walter Koroshetz, director of the neurological disorders division of U.S. National Institutes of Health.
Vaxxinity is arguably the most advanced, having finished a modest Phase 2 trial for its vaccine, UB-311. Leqembi's accomplishment, according to Chief Executive Mei Mei Hu, confirmed a long-questioned theory.
"What we know is that if we knock out certain bad forms of amyloid, we will see an effect in clinical outcomes, and that's amazing," she said of Leqembi's ability to slow cognitive decline.
Data from the 43 volunteers in Taiwan who took part in Vaxxinity's Phase 2a trial, which was released in August, demonstrated that the vaccination was safe and tolerated after 78 weeks and that nearly all of the subjects developed an antibody response. Brain enlargement was not observed in any patients; however, brain haemorrhage, a typical side effect of the infused therapies, occurred in 14% (6) of the cases.
Though Hu said the environment for the last few years as "quite frigid," Vaxxinity has been looking for a partner to assist fund a larger, confirmatory experiment. "The gates have opened with (Leqembi's) approval, and there's a lot more investment and enthusiasm."
The initial Alzheimer's vaccine showed promise, but it also caused the immune system's T-cells—which are solely meant to kill diseased cells—to react erratically.
The majority of the more recent vaccinations target B cells, which are immunological cells that generate antibodies.
The vaccination from AC Immune only stimulates B cells, according to University of Southern California researcher Dr. Michael Rafii.
Meningoencephalitis was not brought on by the AC vaccine in a Phase 1 trial headed by Rafii; rather, a small percentage of subjects experienced an immunological reaction. A modified version is presently being tested by the business.
The CEO of AC immunological, Andrea Pfiefer, hypothesised that the absence of brain haemorrhage or swelling observed with monoclonal antibodies like Leqembi, which peaks after each infusion, may be explained by the prolonged immunological response to the vaccination in certain patients. In 2024, more data is anticipated in the first half.
Additionally, Johnson & Johnson and AC are working together to develop a vaccination that specifically targets tau, a harmful protein linked to Alzheimer's disease and brain cell death.
In an effort to prevent Alzheimer's disease, Prothena, a business that was split out from the original vaccine's co-developer ten years ago, plans to start a vaccine trial for that vaccine next year. The vaccine targets both tau and amyloid beta.
Additionally, Prothena is in Phase 1 studies for an anti-amyloid antibody and has a licence to use an anti-tau antibody from Bristol Myers Squibb.
CEO of Prothena Gene Kinney stated that a substantial amount of mature antibodies are produced by the company's vaccination. Such vaccines, which are normally administered to older people with weakened immune systems, depend on eliciting a robust immunological response, he said.
For those with pre-symptomatic Alzheimer's, he believes immunisations are the best option. "Your goal should be to stop the illness from ever developing in the first place."
(Source:www.bioethics.com)
