Still Searching for Alzheimer’s Vaccine

Despite various clinical investigations, including producing targeted antibodies, no effective vaccine for the prevention or a safe cure for Alzheimer’s exists today.

One of the hallmarks of Alzheimer's is the buildup of amyloid protein, which is key in the pathological alterations in the brain.

Reducing the amyloid burden in the brain has been a pivotal goal in the fight against Alzheimer's.

However, the induction of brain swelling in some patients indicated that a safer route of administration was needed to efficiently treat the disease.

But, the new research suggests that starting Alzheimer’s treatment with a prophylactic vaccine could provide a way of offering treatment before the disease becomes clinically apparent.

In 2013, as many as 5 million Americans were living with Alzheimer’s disease.

Alzheimer’s disease is not a normal part of aging, according to the Centers for Disease Control and Prevention (CDC).

There are several clinical initiatives underway, with various results.  Here is a brief summary of three efforts.

#1

Researchers at the University of Dundee and Oxford have combined the tetanus vaccine with a viral particle that normally affects cucumbers to create a compound that stimulates the immune system.

Tests have shown the resultant vaccine raises antibody levels that are believed to be beneficial in preventing dementia.

Now, scientists are set to begin human trials of the vaccine having received regulatory approval.

Scientists led by Dundee University’s Dr John Foerster and Oxford’s Professor Martin Bachmann were able to take the protein coat of cucumber mosaic virus and incorporate a tetanus vaccine-derived protein structure known to stimulate the immune system in order to create vaccines to treat multiple chronic diseases.

These vaccines can be either preventative - which is the hope for Alzheimer’s - but also therapeutic, meaning they can cure a disease like psoriasis after it has already been established.

“Our research shows that this technique works in mice and, importantly, our new vaccine technology shows that it is likely to be a more effective type of vaccine than existing ones in older people,” said Amy Dalrymple, head of policy at Alzheimer’s Scotland.

“However, this is at a very early stage,” said Dalrymple.

#2

Vitruvian BioMedical, Inc. announced obtaining the Exclusive License for a new Therapeutic Vaccine for Alzheimer’s Disease (AD) from Dr. Yoh Matsumoto from the Immunotherapy Development Inc. in Saitama, Japan and the Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

The AD Vaccine, YM7555, is a DNA Vaccine that targets both ABeta and TAU, which accumulate and are necessary for the development of AD.

YM7555 delivers both genes, which code for the ABeta and TAU, to muscle cells where the corresponding peptide is then made.

The immune system of the individual receiving the genes and making the peptides then makes antibodies against the peptides. The antibodies bind to the peptides and prevent them from accumulating, which could prevent the development and/or progression of AD.

There is increasing emphasis on the need to target both ABeta and TAU for the treatment or prevention of AD.

The AD DNA Vaccine YM7555 has shown a major reduction in accumulation of ABeta and TAU and complete inhibition of phosphorylated TAU, which is the most toxic TAU form, in treated transgenic mice that carry an AD-related gene giving it the AD pathology.

Dr. Yoh Matsumoto is a leader in the field who has created and studied an AD DNA Vaccine for ABeta, which was very effective in inhibiting accumulation of ABeta in transgenic mice, was non-inflammatory and generated a strong immune response in monkeys without toxicity.

Dr. Matsumoto said, “The best strategy for prevention or treatment of AD is to target both ABeta and TAU, since targeting only ABeta has not provided beneficial effects.”

#3

A new DNA vaccine when delivered to the skin prompts an immune response that produces antibodies to protect against toxic proteins associated with Alzheimer's disease, without triggering severe brain swelling that earlier antibody treatments caused in some patients.

Two studies from the Peter O'Donnell Jr. Brain Institute demonstrate in animals how a vaccine containing DNA of the toxic beta-amyloid protein elicits a different immune response that may be safe for humans.

The vaccine, which will likely be tested further by the U.S. Food and Drug Administration, is on a shortlist of promising antibody treatments that may eventually help settle a high-stakes debate of whether amyloid is a vital target for preventing or curing Alzheimer's.

"If you look at the hard reality, the odds are against us because so many therapies have failed through the years. But this has potential," said Dr. Roger Rosenberg, co-author of the studies and Director of the Alzheimer's Disease Center at UT Southwestern Medical Center.

Dr. Rosenberg noted that earlier research established that antibodies significantly reduce amyloid buildup in the brain, but he needed to find a safe way to introduce these into the body.

More information regarding the CDC Healthy Aging Program and The Healthy Brain Initiative to promote independence and wellbeing, can be found here.