We May Be Getting Closer to an Alzheimer’s Vaccine
A new study shows safety and potential benefit for patients with mild disease.
Posted July 21, 2021 | Reviewed by Gary Drevitch
- A vaccine that induces antibodies to clear out pathological tau in the diseased brain can potentially slow down and even prevent Alzheimer’s.
- A new study shows that an experimental tau vaccine is safe, well-tolerated, and can produce a desired immune response.
- More studies are needed to prove the effectiveness of the vaccine in slowing down the disease.
Our immune system in many ways works like my dog’s appetite. If she comes across any food-like item on our walks outside, she will be the first one to sniff it out and gulp it down before I even get a chance to see it regardless of what the item might be (a.k.a. our innate immunity). And yet, at home, my dog will test and build a strategy (a.k.a. antibodies) specific for each available food source. For Cheerios, she will wait at the bottom of the high chair until my toddler inevitably drops some. For turkey slices, she will lick my son’s hands. For lasagna, she will walk around the entire dinner table until she finds that one weak-willed guest who will feed her under the table while I am not looking.
When a pathogen enters our body (or when we are vaccinated), our immune system produces antibodies specific to the harmful intruder to get rid of it. Over the last few decades, researchers have used this mechanism to their advantage—calling it immunotherapy—to fight against diseases such as cancer and autoimmune disorders. Most recently, a study that came out a month ago from a team at Axon Neuroscience based in Slovakia showed that immunotherapy can also be potentially beneficial to one of the most prevalent and incurable diseases of our lifetime: Alzheimer’s.
The promise of immunotherapy for Alzheimer’s disease.
Today, more than 6 million Americans are living with Alzheimer’s. This number is projected to double in the next 30 years. And yet, after decades of research, we still don’t have a cure or even ways to truly slow down the disease. According to Justin Long, an assistant professor of Neurology working on Alzheimer’s disease at Washington University in St. Louis, one of the greatest impediments to developing effective therapeutics is the slow progress of the disease, which encompasses an extended asymptomatic phase that predates the onset of symptoms by as much as 15-20 years. “Clinical trials in Alzheimer's disease often have to follow patients for years to establish whether there is clinical efficacy, resulting in high costs and slow return of results,” he says. "To effectively slow or halt disease progression, there is a good chance that you may need to treat before the onset of symptoms or at the very earliest clinical signs of disease.”
Axon’s experimental vaccine AADVac1—currently the most clinically advanced tau therapy in development—aims to do exactly that. Its goal is to activate our bodies’ defense system to clear out free-floating tau proteins in our brains before they can form harmful tangles that accumulate inside nerve cells and eventually cause their demise. “Tau pathology is a close correlate of cognitive decline and brain atrophy,” says Petr Novak, a senior clinical research scientist at Axon. If it works, the vaccine can stop the progression and spread of these tangles, and thus could provide symptomatic relief to patients with early or mild disease. If administered early enough, it could even prevent the disease. But first, it has to prove its safety, immunogenicity (i.e. capability to create an immune response), and of course, efficacy.
The study shares results from a two-year-long Phase II clinical trial with 196 patient participants across eight European countries. It shows that AADVac1 is safe, well-tolerated, and can generate a strong tau antibody response. Participants who received AADVac1 had a drop in neurofilament light chain protein—“a marker [for] the intensity of neurodegeneration” according to Novak—in their blood, as well as a reduction in tau in their cerebrospinal fluid compared to those who received the placebo control. While these are promising results, the study failed to demonstrate a significant cognitive benefit on thinking, reasoning, and memory tests performed across the entire patient group. According to Novak, this was not due to the vaccine’s inefficacy but an error in trial enrollment where “a non-negligible number of patients negative for tau biomarkers made it into the study confounding analysis.” The group is planning to follow this study with a longer and larger clinical trial to prove AADVac1’s effectiveness in slowing down cognitive impairment in mild Alzheimer’s disease.
Tau vaccines may be the future for Alzheimer’s therapeutics, but they need more time to prove themselves.
Regardless of the study’s results, Long believes that therapies that aim to lower pathologic tau in the brain make sense and that antibody-mediated clearance is a good strategy to do it. “I am excited for the potential of tau-based therapies,” he adds, while warning, “I do not expect the pathway to be smooth and I am sure there will be some roadblocks to developing effective therapies along the way.”
Novak agrees. “The first generation of disease-modifying treatments will likely not fully halt the disease,” he says, “but once there are treatments that are confirmed to be truly efficacious, we can start testing them in asymptomatic [Alzheimer’s disease] patients to evaluate their preventive properties.”
Like a juicy steak my dog has yet to ingest, finding effective therapies to treat or prevent Alzheimer’s disease is a dream we all want to come true as soon as possible. Vaccines may be able to get us there sooner than later.
LinkedIn image: Koldunov/Shutterstock