Potential Vaccine Leads to a Brighter Future for Alzheimer’s Disease

Alzheimer’s disease and dementia related illnesses are amongst the most crippling in our health system, with a global cost of over $US600 billion a year. With the amount of Alzheimer’s cases increasing by 7.5 million a year, this cost is only going to grow. The current 48 million people diagnosed are victims of the costliest illness worldwide, causing a huge strain on the global health system and draining our global economies.

Not only does this affect us economically, it drastically alters the lives of those diagnosed and their loved ones. Alzheimer’s disease usually appears in patients of 65 years or older (although early-onset Alzheimer’s can appear in those in their 40’s or 50’s). At this time most are making the transition to retirement and experiencing the introduction of a new generation of grandchildren; but many Alzheimer’s patients do not even remember that they have grandchildren. Unfortunately, this memory loss is usually accompanied by confusion, anger, dangerous behavior and mood changes, and disorientation. This burden is heartbreaking for families as they essentially lose the people that they love the most. 

What exactly is Alzheimer’s disease?

According to the Alzheimer’s Association, Alzheimer’s disease is “a general term for memory loss and other intellectual abilities serious enough to interfere with daily life”. It is the most common form of dementia, accounting for 60-80 percent of all cases. Generally, people live an average of eight years after diagnosis of Alzheimer’s, although some have lived as long as 20 years. What starts with mild mood changes and memory loss, progresses to full deterioration of the brain accompanied by the loss of the ability to communicate, recognize any caregivers and family members, and the ability to take care of themselves. The disease and all it encompasses is truly devastating.

On a molecular level, neurons seem to be the main type of cell destroyed by Alzheimer’s disease. This occurs through the interference in the delivery of electrical impulses between neurons as well as neurotransmitter release. This causes a disruption in the normal connections of nerves in the brain, changing the way that the individual interprets daily situations. Eventually, progressed Alzheimer’s disease will lead to the death of the nerves, and thus an overall loss of tissue and subsequent shrinkage in the brain – the greatest of which appears in the cortex, the largest part of the brain. In particular, the hippocampus, responsible for the formation of new memories, shows the greatest shrinkage. This, therefore, is the cause of memory loss and the inability to recall current and past events in the patient’s life.  

As to the exact cause of Alzheimer’s, scientists have been butting heads over the answer for years. However, recently a majority of scientists have agreed that the main pathogenesis of the disease is a combination of β-amyloid and tau protein. In the initial stages of the disease, there is a buildup of β-amyloid plaque, which interrupts brain signaling and triggers immune responses that cause further inflammation and cell death. 

As the disease progresses, there is a subsequent increase in a second protein, known as tau. Tau protein collapses into twisted fibers that build up in the cells, forming tangles. These tangles directly interfere with the transport system in proteins, therefore interfering with the transfer of food molecules and other cell parts that are vital to the functioning of the cell. The discovery of these proteins has been revolutionary to Alzheimer’s research, as it has given scientists a potential target to act on in preventing and curing Alzheimer’s disease.

The past 

A study in Alzheimer’s Research and Therapy concluded that between 2002 and 2012, 413 Alzheimer’s disease trials were performed. Out of these trials, only one drug was approved for human use, but its failure rate was a shockingly high 99.6%. Even the website for the drug, known as NAMZARIC, has a striking disclaimer, stating that “there is no evidence that NAMZARIC prevents or slows the underlying disease process in patients with Alzheimer's disease”.

According to a Consumer Report study in 2012, “the available studies indicate that most people will receive no benefit at all from taking an [Alzheimer’s disease] medication”. The study continues to state that due to a “relatively high price tag and the risk of side effects, including rare but serious safety concerns, we cannot endorse any of the medications”. This means that there is currently not a single drug that can cure, prevent or even manage the symptoms of Alzheimer’s disease. Those diagnosed have no options but to succumb to their illness.   

Despite these facts, most people don’t know that Alzheimer’s disease is incurable. This is most likely due to a misrepresentation of findings to the public. In the past, many studies of the aforementioned drugs have shown measurable changes in the brain, but do not accurately represent any changes in the life of the patient. This delivers deceiving information to the public, as we think that these findings are valuable. Not only do the drugs have little result, but add in the risk of major side effects such as extreme liver damage, drastic weight loss, chronic dizziness, lack of appetite, stomach pain, and many more minor side effects, and the risks out weight the limited benefits. It is because of this that 20-25% of patients eventually stop taking their medication. Not to mention that these drugs can cost patients up to $US400 a month.

The vaccine 

It is no secret that something needs to change. The United States alone has committed $US1.3 billion to Alzheimer’s research this year with nothing to show but successive failures and limited results in drug treatments. This has left a desperate plea for something drastic and different. It seems that Australian researchers at Flinders University, alongside U.S. scientists at the Institute of Molecular Medicine (IMM) and the University of California at Irvine (UCI), have responded to this plea for help. The team is on their way to developing a vaccine that will treat Alzheimer’s disease.

As previously stated, β-amyloid plaque buildup and tau protein tangles have recently been named the cause of Alzheimer’s disease. Nikolai Petrovsky, Professor of Medicine at Flinders University in Adelaide, South Australia and part of the team developing the vaccine, further explains that the function of the proteins in causing Alzheimer’s disease has been demonstrated in transgenic mice. 

“These transgenic mice get an accelerated form of dementia mimicking human Alzheimer’s
disease,” said Petrovsky. “Therapies including vaccines and monoclonal antibodies that block accumulation of β-amyloid or tau [proteins] in these mice stop them developing dementia, confirming the causal role of build up of these abnormal proteins.”

Therefore, to successfully prevent the disease, or treat it in the early stages, a potential vaccine would have to initially interfere with β-amyloid by directly targeting the plaque build up. In order to treat at later stages of the disease, the vaccine would have to interfere with the functioning of the tau proteins. To solve this problem, the scientists had to discover a vaccine that would interfere with both, either simultaneously or sequentially.

Thus the team set out to discover a vaccine that would successfully interact with the proteins at the necessary time to be effective, using post-mortem Alzheimer’s patient’s brains. The findings of their study, released in Scientific Reports in July 2016, confirmed that a vaccine like this was possible using two ingredients that proved to be crucial for its development. The first was a sugar-based adjuvant called Advax^CpG. According to Petrovsky, the use of this adjuvant “helps provide the B cells with maximum stimulation to produce specific antibodies.” This was joined with a second vaccine platform, known as MultiTEP technology. This was “designed to provide maximal T cell help to the antibody producing B cells, thereby helping ensure the vaccine provides sufficiently high antibody levels to be effective.”

A brighter future

Thanks to the Flinders University team and the Institute of Molecular Medicine, the future of Alzheimer’s disease research is showing promise. Their recent results will lead the way for the future of Alzheimer’s Disease Research, which has previously been known as a “graveyard for expensive drug tests”.

The vaccine developed by Petrovsky and team has shown to induce more than 100 times the amount of antibodies than drugs that have failed in the past. The team achieved this by creating a vaccine with the perfect 3D shape that will induce the antibodies needed to bind to β–amyloid and tau proteins appropriately. Petrovsky states, “This was not done for many of the failed candidates which most likely, thereby, did not produce either sufficient antibody or the right type of antibody.”

Petrovsky anticipates that “the vaccine will begin human clinical trials in approximately two years. If shown to be effective in such trials we would expect it being on the market in about seven years.”