A major breakthrough in Alzheimer's treatment! The clinical data for the no-invasive black technology Phase 2 of MIT Neuroscience Bull were published, and the six-month treatment significantly delayed the decline in cognitive function by 83% | Clinical discovery

Every time we introduce potential innovative therapies, Singularity Cake will always add a sentence at the end, hoping that it can be applied to the clinic as soon as possible to benefit patients.

But Singularity Cake understands that the research and development time of new therapies is often ten years, and when it encounters some recognized indications of "tiankeng", with the help of the whole world, a new drug cannot be produced in ten or twenty years.
never seen it.

The “black technology” I’m going to talk about today, since its emergence in 2016, singularity cakes have been very concerned.
Although they are very optimistic about its prospects, they did not expect that in just five or six years, it will be Able to obtain clinical transformation and achieve quite dazzling results in clinical trials.

It's still on the famous tiankeng-Alzheimer's disease (AD)! At the 15th International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD™2021) held recently in 2021, Cognito Therapeutics announced the Phase 2 clinical study data of digital therapy gamma frequency neuromodulation.
This therapy was born out of the findings of the MIT neuroscience big cow Cai Lihui and the optogenetics big cow Edward S.
Boyden's team that we have introduced before.
40Hz sound/stimulating light can reduce the beta amyloid in the brain and improve cognition.

According to the currently published data, a 1-hour-a-day, 6-month treatment can significantly delay the disease progression of patients with mild to moderate AD, the activity of daily living scale (ADCS-ADL) score decrease by 84%, and a simple mental status check The decline in MMSE scores has slowed by 83%, and brain atrophy has been significantly reduced by 61%! [1] This data can be said to be very, very beautiful.
The singularity cake represents the envy and jealousy of other colleagues who are also struggling in the sinkhole.

And this therapy is performed through a device called GammaSense, which is completely non-invasive, and the corresponding safety and tolerability are good (saliva again).

Get up, get up quickly! ▲It is only a schematic diagram.
It has nothing to do with bose and VIVE.
The black technology can be regarded as a singularity cake.

In 2016, the emergence of that "Nature" paper was really shocking.

Unfortunately, Eli Lilly had just officially announced that it had invested hundreds of millions of dollars in research and development of the new AD drug solanezumab Phase 3 clinical trial failure.
Before that, countless ancestors had fallen on the road of AD drug research and development.

According to an analysis of data, between 1998 and 2017, 146 new AD drugs worldwide failed in clinical trials, with a clinical success rate of only 2.
7% [2].

At present, there are only 5 kinds of AD treatment drugs approved by the FDA (including a compound preparation), all of which can only improve the symptoms of AD and cannot really delay the disease process.

The repeated failures of new drugs and the successive failures of top companies with first-class research and development capabilities have even made some scholars wonder whether there is a mistake in our cognitive basis of AD.

In contrast, the population suffering from AD is extremely large.

According to epidemiological investigations, there are more than 7.
5 million AD patients in my country, and it is estimated that it will exceed 20 million by 2050 [3].

The number of deaths due to AD in my country has increased by 57.
8% in the past ten years, making it the fifth leading cause of death in 2016 [4].

There are too many patients, and there are too many shortages of new drugs.

Tiankeng, it is really a tiankeng.

At this time, the emergence of the "Nature" thesis really shocked the little mind of Singularity Cake.

It's not that it has solved some terrifying difficulties all at once, but at first glance, it is really a bit unreliable! In the face of AD with complex mechanisms and numerous potential targets (but none of them are effective), the solution presented in this paper turned out to be LED lights? [5] In this study, Dr.
Cai noticed a phenomenon that in patients with brain damage, schizophrenia, and AD, the brains of patients with diseases such as brain damage, schizophrenia, and AD, etc.
, often have confusion in gamma brain waves with a frequency of 30-90 Hz. Brain waves can be said to be the visualization of neuronal connections in the brain.
The disorder of gamma waves is likely to mean the disorder of neuronal function.

This makes the researchers wonder whether the normal function of neurons can be restored if the gamma wave can be restored by certain means? ▲Comparing the brain gamma waves between healthy people and AD patients, the difference is indeed obvious.
The initial attempt was achieved through optogenetics, that is, to regulate neuronal activity through implanted optical fibers and photoreceptors on nerve cells.

The results of the experiment are very surprising.
Using a frequency of 40 Hz and only one hour of treatment can reduce the β amyloid in the brain of AD model mice by 40-50%! In fact, this step is shocking enough, but to be used clinically, a less invasive method is needed.

The researchers thought, what about using external light sources, through the eyes, the light can also reach the depths of the nerves! Sure enough, using an LED lamp with a light source frequency of 40 Hz to irradiate mice, the γ wave frequency of the visual cortex of the mouse brain really kept up with the rhythm, β amyloid protein clumps and monomers were reduced, and the concentration of tau protein was also reduced.
.

▲External light sources can activate brain nerves through the eyes.
This "Nature" paper is just the beginning of a series of studies.

More than two years later, the research team published a "Cell" paper [6], pointing out that in addition to light stimulation, 40Hz sound stimulation can also reduce β amyloid in the mouse brain, and the range of stimulation is wider.

Light can only affect the visual cortex, while sound can touch the auditory cortex and the CA1 area in the hippocampus.

Combining sound and light can achieve the effect of 1+1>2, further expanding the scope of the brain area affected.

After 1 hour a day and one week of treatment, the total plaque volume of the mouse prefrontal cortex was reduced by 37%.

Because the picture of listening to the song while illuminating the light bulb is too strong, many readers also joked, saying that this therapy is called "Beng Di Zhi AD" forget it.

▲True and shining lamp ball As for how this thief is unreliable at first glance, but the effect is wonderful, a follow-up paper published in the "Cell" sub-Journal "Neuron" magazine[7] A detailed answer is also given.

It turned out that the regulation of gamma waves mainly induced scavengers in the brain, changes in the morphology of microglia and changes in gene expression, reduced the inflammatory response of microglia, and also had a protective effect on neuronal synaptic function.

As early as 2016, Cai Lihui and Boyden established Cognito Therapeutics to transform this scientific research result and developed a medical device called GammaSense.

Today, the results of its Phase 2 clinical OVERTURE trial have also been announced.

According to the trial design published by clinicaltrials.
gov[8], the OVERTURE trial is a phase 1/2 randomized controlled, single-blind multicenter study, which is expected to recruit 60 patients with mild to moderate dementia (MMSE score 14) over 55 years of age.
-26) The subjects were randomly assigned to the treatment group and the control group according to 2:1, and treated for 1 hour a day for 6 months.
The control group used fake equipment.

The trial will use the Mini Mental State Examination Scale (MMSE) and the Activity of Daily Living Scale (ADCS-ADL) to assess cognitive and memory function, and structural magnetic resonance imaging (MRI) to assess changes in brain volume.

The published clinical trial data showed that 76 patients with mild to moderate AD over the age of 50 were actually recruited.

During the 6-month treatment period, γ-frequency neuromodulation therapy was safe and well tolerated; compared with the control group, the ADCS-ADL score of the treatment group decreased significantly by 84%, and the MMSE score decreased by 83%, which is related to AD The brain atrophy and brain volume loss were reduced by 61%.

In view of the significant improvement of brain atrophy, it can be considered that gamma frequency neuromodulation therapy is likely to really change the course of the disease.

If it is verified in a larger-scale study, it will undoubtedly bring a huge medical breakthrough to the treatment of AD.

At the same time, this will also be the first digital therapy to truly delay AD.

I have to say that Cognito Therapeutics has done a good job of confidentiality.
For several years, Singularity has not been able to know what this mysterious GammaSense device looks like from the Internet.
I can only guess from the text of the paper.
It may be similar to VR glasses.

▲There will be an online discussion meeting on AD/PD2021 this Friday.
During the search, Singularity really found a wearable device marked with 40Hz sound and light stimulation (absolutely no authorization) (more than 200 dollars seems to be a little bit) Conscience), I would like to remind everyone that the γ-frequency neuromodulation therapy has not yet been officially approved by the FDA.
If there are devices that are sold under the corresponding banner, do not rush to buy them.

In fact, Cognito Therapeutics has obtained the FDA's breakthrough medical device certification in January this year[9].
If it goes well, we will be able to see its true colors soon. Reference: [1] https:// Lao K, et,al.
J Drug Target.
2019 Feb;27(2):164-173.
[ 3] Jia J, Wei C, Chen S, etal.
The cost of Alzheimer's disease in China and re-estimation of costs worldwide[J].
Alzheimer's Dementia, 2018,14(4):483-491.
[4] Zeng Xinxin ,Qi Jinlei, Yin Peng, et al.
Report on the burden of disease in China and provincial administrative regions from 1990 to 2016[J].
Chinese Journal of Circulation,2018,33(12):1147-1158.
DOI:10.
3969/j.
issn.
1000-3614.
2018 .
12.
002.
[5] Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, et al.
2016.
Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Nature 540: 230-5.
[6] Martorell AJ, Paulson AL, Suk HJ, et al.
Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition[J].
Cell, 2019, 177(2): 256-271.
e22.
[7] Chinnakkaruppan A, Steven J.
M , Asaf M, et al.
Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection[J].
Neuro, 2019.
DOI:10.
1016/j.
neuron.
2019.
04.
011[8] https://clinicaltrials.
gov/ct2/show/NCT03556280[9]https :// -Disease Author of this article | Dai Siyu