Breakthrough ultrasound treatment to reverse dementia moves to human trials | Hacker News Reader

Breakthrough ultrasound treatment to reverse dementia moves to human trials

newatlas.com

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Ok so the article says this successfully destroys the amyloid plaques, but does it help cognition or slow the disease?

Specifically for “slowing” it seems entirely plausible that breaking up the plaques will allow misfolded proteins to migrate (due to reduced size).

Ignoring entirely the there have been multiple drugs that successfully reduced amyloid build up, with no actual benefit. Eg they did exactly what they were designed for to no avail.

It’s moving to a phase I trial, that means it’s just being tested for tolerability and adverse effects. A firm conclusion about outcome won’t be available until a phase III trial is completed, that’s years down the line. So we don’t know, but looks promising.

Assuming this gets "breakthrough therapy" designation how many years down the line will it be available ?

Well it's not a drug, and I assume that they're using previously approved medical devices to apply it. It seems to me to be more like a new surgical technique. In that case it may just be a matter of finding a physician willing to apply it, though without safety or efficacy data I would expect that number to be hovering around zero.

It says more than that:

"the team has worked to further test and refine the technique, successfully proving the treatment both clears toxic proteins and restores memory function safely in several different rodent models, including an older mouse model designed to resemble human brains of 80 to 90 years old."

The information around Alzheimers seems to be heading the direction that the beta-amyloid plaques are an immune response to the HSV1 herpes virus that help prevent the spread of the virus.[1]

I suppose it can't be ruled out yet that this immune response could still cause damage, but it does make me wonder if the plaques are actually responsible at all for the symptoms seen, since like you said, other drugs reduce the plaques with no improvement in symptoms.

It's interesting that this treatment seems to work when others do not- when they seem to be accomplishing the same thing (reduction of beta-amyloid plaques)

[1] http://www.virology.ws/2018/11/08/herpes-simplex-virus-and-a...

Your claim is far too strong, that is merely one theory, evidenced by a posted link from/by/for virologists. There is not a field-wide consensus to support that by any stretch.

I don't think I made any strong claims myself? I guess "Seems to be heading the direction" implied too much of a consensus? The fact that antiviral drugs helped- does seem to lend a good amount of credence to the theory though?

I've just seen the theory come up a number of times, from a number of locations, in the past few months, so that gave me an impression that it was gaining ground.

There's a theory on beta amyloid that it's merely the by-product of other causative agents, and that as a surrogate end-point for Alzheimer's outcomes, it's not nearly as useful as symptom reduction, as you state. My professor who studied AD and dementia likened beta-amyloid to the garbage leftover in a stadium or outdoor concert: you know something went down, this leftover trash isn't great, but hard to determine what actually did occur just based on beta-amyloid.

Of course, the AD research field is still divided and there are many competing theories. Solving AD and dementia is one of the greatest challenges in modern science.

Plaque on your teeth is a symptom too:

Do what you can daily, but let a dentist break it up periodically.

Alzheimer is weird in that plenty of treatment works in mice but fails in humans. I suspect it's primarily because we do not fully understand the cause of Alzheimer.

Why do you think that is weird?

My understanding is that "mice studies" cost less than clinical trials, therefore more "mice studies" with (correct/incorrect) conclusions are created.

Most likely there is no singular cause, but a slew of contributing factors that prevent amyloid clearance and promote plaque formation. That's why overlapping, holistic solutions like the Bredesen protocol, ketagenic diets and now possibly ultrasound are the best treatment than waiting for a panacea that is unlikely to ever exist.

And don't forget the vipassana and rolfing!

Conversely it would be shocking if most things that work on mice worked in the same ways on humans.

what are you thinking of specifically? I mean genetically and functionally we are incredibly similar as mammals. Most poisons/etc. work the same for example.

I'm completely speculating, but I think when your lifespan is only 2 years anyway, you have almost no selective pressure for things like the kinds of diseases of aging that humans are now battling. So there are all kinds of things like cancer and dementia that mice's systems are much more naive to, and hence they are tend to get sick from "simple", easily treatable versions of these diseases. Meanwhile humans have evolved strong defenses for all the common / simple causes and are trying to fix the "hard" versions of all these things.

It's partly because of a more complex version of that, partly because of evolutionary drift.

Mammals can still be incredibly distinct when you get down to specific biological pathway behavior. Or they can be exactly the same. Depends on how the mutation dice came up.

For example, the different ways various mammal species metabolize theobromine [1] (aka, the "dangerous" thing in chocolate).

Dogs and humans are similarly allergic, but because we metabolize it differently it's eliminated from our bodies much more quickly, which keeps it from building up to dangerous levels.

As my dad (vet / path / drug development) would say, 'Mother Nature is lazy before anything else. She'd rather repurpose an already evolved system than create something new in almost every circumstance.'

Multiply that by ~95 million years (last common dog-human ancestor), and you get a lot of quirky genetic code debt. ;)

[1] https://www.ncbi.nlm.nih.gov/m/pubmed/6144479/

There's some evolutionary pressure in the form the selective breeding of animal models of human disease; it just has not been very successful for Alzheimer's. I guess you have to start with what nature gives.

I saw a lecture recently that sought to compare the difference between mice neurons and human neurons. They were surprised to find that the capacitance of the neural membranes was substantially different. They showed that populations of human neurons we're capable of entraining to frequencies exceeding 1000hz, whereas mouse neural populations capped out below 300hz. I apologize I don't remember the researchers name, but it was at a Human Brain Project conference in Amsterdam.

Out of curiosity, is that property specific to mice, or are most small mammals similar in that regard, and we use mice instead of, say, cats, just because they are more convenient?

This is because our mouse models of Alzheimer disease are terrible. And pretty much everything we've tried has been aimed at beta-amyloid.

I think there is a better chance for this therapy because of the way it works, by transition the microglia over to an anti-inflammatory mode.

If this procedure passed safety trials I wouldn't be surprised if a similar therapy worked for schizophrenia, anxiety, and depression.

I agree that various kinds of immune modulation will be a huge part of medicine in the future. Promising results vs cancer, seems plausible you could teach or program the immune system to attack anything in the body once you’ve identified it. Controlling autoimmunity will also be a challenge.

They've already started doing this with cancer. The problem is the cancer evolves to stop producing the identifiers the immune system was using to determine what to kill.

Is there speculation on what this would do to a healthy brain?

Probably more harm than good- you probably don’t want ultrasonic waves shaking your neurons around without a good reason. This sounds like a “kick a TV and it works again” sort of technology.

Who knows? Maybe certain modes of damage can result in something akin to hypertrophy in muscle?

I don't think this is a kick the TV type of technology. It's causing the microglia to activate, and I doubt it's causing any neuroinjury. Because the last people you want to injure are people with Alzheimer's.

Many treatments of severe conditions do substantial harm, which is considered acceptable for the benefits.

Extreme examples are chemotherapy, i.e. giving poison to cancer patients, and radiotherapy, i.e. irradiating them. The healthy cells can take it, the cancer cells not so much. Statistically.

Yeah but this isn't chemotherapy, and with chemotherapy you are literally trying to kill cells.

A distinction without a difference. What I meant was: it may be worth it to cause some neural damage to defuse whatever mechanism causes a disease that, when unstopped, causes more neural damage. Hence "kick the TV" technologies are not out of consideration.

Obviously, very big ethical issues arise when experimenting on people, but that's nothing new. Someone took radiotherapy first, before anyone was sure it was worth it to the individual.

My first thought: Great, an ultrasonic brain cleaner. Back in the day, I used an ultrasonic homogenizer for mitochondria preps. But this would be a lot gentler, I guess.

You might not need ultrasound though, eg https://www.nature.com/articles/d41586-018-02391-6.

I can't find the link now, on mobile, but I found reference to using low frequency sound/light and that (anecdotally) individuals had tried this with their Alzheimer suffering relatives and had great success, like miraculous recovery of memory.

I wonder if there is a natural occupational exposure (CRT TV?) that could give evidence here, like if fewer people long-term exposed to low frequency sound/light get Alz?

Related: prenatal ultrasound could be significantly damaging, https://www.pnas.org/content/103/34/12903.full.

There was a great Radiolab episode about the lower-frequency stuff. IIRC, the hypothesis there is that you can stimulate certain types of brainwaves that tend to run on similar frequencies, so that seems like it's probably working via a separate mechanism from the proposed effects of the ultrasound treatment, since ultrasound is way too high-frequency to correspond to any known brainwave frequencies. Perhaps both treatments could be complementary, though, assuming they both pan out.

Mental percussive maintenance?

Indeed; the 'open the blood-brain barrier' motivation sounds fscking scary; the barrier is there for a reason, and you'd be opening yourself to totally unknown risks in the process.

The first thing that came to my mind was how some people with kidney stones are treated with shock waves that breaks them up.

Sounds promising and I hope it works. But until its proven to work well in humans I won't get exciting about it

https://www.foundmyfitness.com/episodes/dale-bredesen

Rather than just posting a link, it would be helpful if you would give a brief explanation of what you find useful or interesting there.

https://www.youtube.com/watch?v=qQhUxd82Rr0

Wow. This is amazing. My 96-yo grandmother could really try this because anything that could potentially improve her QOL would be good.

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