Alzheimer’s disease (AD) is a complex neurological disease that is the most common form of dementia, or loss of brain function. Individuals suffering from Alzheimer's display impairments in learning and memory, as well as changes in personality and mood. According to the World Health Organisation, dementia is currently the fastest growing global health epidemic. AD is most often diagnosed in people that are older than 65, although there are a few rare cases of early-onset of the disease. The prevailing hypothesis about the cause of AD involves the protein amyloid precursor protein (APP), which is found in the outer membrane of nerve cells and that, instead of being broken down, forms a harmful substance called beta-amyloid. This noxious version of the protein can accumulate as plaques and kill brain cells. Needless to say, the disease is devastating to many all over the world, and a huge cost for society.
Researchers around the world have been investigating genetic and environmental factors that may put individuals at risk, as well as how beta-amyloid can cause neurodegeneration. Moreover, other theories besides the APP theory exist to explain the cause of AD. While there is currently no cure for the disease, scientists have been trying different approaches to treat the disease; one of them has been vaccines. The first vaccination study conducted almost a decade ago, showed some efficiency in clearing up beta-amyloid plaques, but did not help with dementia at all. Furthermore, the vaccine caused too many adverse side effects, including an autoimmune reaction, and was soon abandoned.
A recent study from researchers at the Karolinska Institutet in Stockholm points to the first successful attempt at a vaccine treatment for AD. The new treatment is an active vaccine and the idea is to use a type of vaccine designed to trigger the body's immune defence against beta-amyloid. In this set of clinical trials, the vaccine was modified such that it only affects the harmful form of APP, that is beta-amyloid. The investigators observed that 80 per cent of the participating patients developed protective antibodies against beta-amyloid, without suffering any side effects that were observed in previous trials of this study. The researchers believe that the treatnent, called CAD106 vaccine, could be an effective and tolerable way to treat patients with mild to moderade AD. More large-scale clinical trials have to be conducted to further determine the efficacy of CAD106, but the discovery is very encouraging for AD patients and their families.
I'm going to attempt to participate in your blog. This might get messy. From an immunological perspective, the idea of making a vaccine against beta amyloid is interesting, but I'm quite skeptical.
ReplyDeleteGenerally, the brain is assumed to be an "immune privileged site", meaning that it is not monitored by the immune system in the same way as are most other tissues of the body (another classic example of a privileged site is the eye). This is why we think microglia are so important in the brain. No other classic immune cells are believed to be able to cross the blood brain barrier. As far as I know, antibodies in blood circulation are also not able to cross the barrier. I would be willing to bet that in the vaccine trial, they simply measured blood concentrations of antibody against beta amyloid. Thus, they have not proved that the protective antibody would get to the intended site.
In the case of an immunological disease that affects that brain, like multiple sclerosis, scientists hypothesize that there is a source of chronic inflammation that opens up the blood brain barrier to enable immune cells and antibodies (in this case, self-reactive and harmful) to get into the brain and induce damage. It's not clear, however, that slow buildup of beta amyloid plaques in a person would induce any kind of inflammatory danger signal that would allow the immune system to access the brain and neutralize the plaques.
As you mentioned, they've really only completed the very first step: demonstration that you can generate amyloid specific antibodies in people. Some immunologists have even recently begun to question whether the hallmark of a good vaccine response is the production of antibodies. It's definitely a novel idea. I just wonder if it will end up justifying the significant costs of the study.
Thank you for your comment Alex! You've pointed out some very interesting things, and you're definitely right that this is just the first step in showing that the body is capable of developing antibodies against beta amyloid. While the main objective of the study was to assess safety and tolerability of the vaccine, it will be interesting to see whether the vaccine has any effects on beta-amyloid clearance and dementia.
DeleteThe point you make about the peripheral immune response to beta amyloid build-up is interesting. There is some evidence that points to microglia, the resident immune cells in the CNS, being activated by beta amyloid. At the risk of opening a can of works, microglia play a complicated role in AD pathology, one that can be detrimental (by causing phagocytosis and therefore cell death and injury) or protective (by mediating inflammatory responses that help in plaque clearance). Nonetheless, it could be a possible target for therapeutics.
As far as this study being cost-effective, I suppose one would hope that they interpret their results with caution and plan the next phases of their trail accordingly.