Thursday, March 12, 2015

Non-Invasive Treatment as a 'Breakthrough' for Alzheimer's: Too Good to Be True?

The claim of a 'breakthrough' is sometimes used too liberally in pop culture science – but researchers have recently found a method that can have major future implications for Alzheimer's Disease, and they're serious about it.

These researchers have found a method for improving memory in mouse models of Alzheimer's Disease solely by ultrasound. Dementia, the most common presentation of Alzheimer's, affects almost 50 million people worldwide, a number that is set to reach 135 million by 2050, according to Alzheimer's Disease International. A new approach is needed now more than ever.

To test the proposed treatment, the researchers first injected mice with amyloid-β, the peptide implicated in the development of Alzheimer's, to create models to test this treatment. It has been proposed that if amyloid-β can be removed in Alzheimer patients, memory will improve. So the researchers did just that.

From BrightFocusTM Foundation
http://www.brightfocus.org/alzheimers/about/understanding/plaques-and-tangles.html


The test mice were treated with repeated scanning ultrasounds to ultimately remove amyloid-β. Specifically, the rapidly oscillating waves of the ultrasound activate microglial cells in the brain, which then digest and remove amyloid-β plaques. The removal of these plaques is a vital step to this method, as they destroy the brain synapses necessary for memory.

The scientists found that the amyloid-β plaques were almost completely cleared in 75% of the ultrasound-treated mice, and further, that these mice displayed improved performance on three different memory tasks. Their newfound abilities to perform these tasks even matched the performance of normal, healthy mice.

What's so exciting about the efficacy of this new technique is that it doesn't involve any drugs, which thus far have showed rather unimpressive effects in Alzheimer's patients. They only work short-term and don't specifically target amyloid-β. The team believes that if this treatment is applied early, it can be much more effective than the traditional pharmacological approach.

So what does this imply for humans with Alzheimer's Disease? This approach has only been found effective in one experiment using mice, and it is even unclear as to whether the amyloid-β plaques are a cause or merely a symptom of Alzheimer's. Should we be getting our hopes up?

Not just yet, says the team. They are well aware that this technique is far from being used in humans – clinical trials are set at about two years away. Prior to even testing in humans, researchers will also have to investigate long-term side effects as well as the treatment's functionality in thicker skulls and larger brains.

Scientists also want to further test the treatment to see if it has potential uses in other neurodegenerative diseases, and if it can also lead way for the restoration of more executive functions, such as decision-making and motor control.

For now however, the next step of this particular method's efficacy towards Alzheimer's is to test this method in sheep, the results of which should be expected later this year.

Like any scientific discovery, it doesn't mean that a cure has necessarily been found for Alzheimer's. However, this is a huge step in rethinking the methodology of the treatment of Alzheimer's as well as other major debilitating neurodegenerative diseases.

Professor Jürgen Götz, the director of Clem Jones Centre for Ageing Dementia Research, says "The word 'breakthrough' is often mis-used, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach."

Read the paper itself here.

References:
Leinenga G. and Gotz J. Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. Sci Transl Med, 7:(278), 278ra33 (2015).

5 comments:

  1. I wonder why the number of Alzheimer's patients is increasing. One might suspect that it could be related to increased longevity so more people are likely to live long enough to develop Alzheimer's. However, I have read that Alzheimer's might be a prion disease, infectious proteins. If this is true, then could there be a mode of transmission, like eating cows with bovine spongiform encephalopathy, causing the spread of Alzheimer's. Maybe all we need to do is figure out how the prions are being transferred. That would explain why the ultrasound is only a short term solution.

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  2. This is so interesting! How long is the ultrasound treatment effective? Are there any negative side effects? These are questions that are hard to come up with before testing on humans, but it is cool that they are moving on to different mammals!

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  3. This a very interesting and unique approach to a disease that appears insurmountable, although I have a few pathological questions that make me skeptical as well. Mostly, I wonder if the authors addressed Tau or neurofibrillary tangles? There are many hypotheses regarding the molecular mechanisms driving neural degeneration in Alzheimer's, and although Ameloid-beta has been the leading hypothesis for years, more recent evidence suggests that Tau hyperphosphorylation may precede A-beta plaque formation; and if this is true their treatment would likely only be a temporary relief. Additionally, I wonder if this would improve memory or prevent further decline since as Alzheimer's progresses their is significant neuronal loss and it is unclear whether or not the brain would be able to regenerate after substantial cell loss in the areas most affected by the disease. Overall a very cool idea I would like to learn more about!

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    1. I agree with paige that this is an interesting approach, however it does not take the full scope of the disease into account. The disease also features tau tangles which have been more a a focus in recent research. Many researchers now believe that the tau tangles may come before the amyloid-beta. An interesting area of research is how CTE is related to Alzheimer's Disease. In CTE, researchers think repeated head injury causes the dysfunction of tau, which them spreads to other areas of the brain, eventually causing AD. While this treatment is interesting and should be further investigated, people should be aware that it does not address all of the biological features of the disease so probably will not alleviate all symptoms.

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  4. It is exciting to hear about so many new and promising approaches to treating Alzheimer's. Although getting a treatment to market, especially in the case of a disease with a progression like Alzheimer's is a long process, it seems very possible that we are on the verge of a breakthrough and that sometime in the near future we will have effective treatments if not a cure for this devastating disease.

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