Huntington’s breakthrough may stop disease

Huntington's disease (HD)... is an inherited disorder that results in death of brain cells. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. As the disease advances, uncoordinated, jerky body movements become more apparent. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia. The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age, but can start at any age. The disease may develop earlier in life in each successive generation. About eight percent of cases start before the age of 20 years and typically present with symptoms more similar to Parkinson's disease. People with HD often underestimate the degree of their problems.

See Wikipedia: Huntington's Disease for full citation

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The disease affects the protein Huntington and instead of creating more proteins (the protein is beneficial, normally) it turns and attacks brain cells.

The defect that causes the neurodegenerative disease Huntington's has been corrected in patients for the first time, the BBC has learned.

An experimental drug, injected into spinal fluid, safely lowered levels of toxic proteins in the brain.

The research team, at University College London, say there is now hope the deadly disease can be stopped.
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Some patients described it as Parkinson's, Alzheimer's and motor neurone disease rolled into one.

BBC.com, Health, Dec. 11, 2017 - Huntington’s breakthrough may stop disease.

There is segment of mRNA (messenger RNA) that begins to transcribe the DNA for replication incorrectly. The result is HD and the slow decline of the patient.

The study, in 46 humans, has the medicine injected into the spinal fluid and/or brain fluid directly. The drug kills the bad mRNA strands preventing from the spread of the disease. In some cases even reversal of motor function have been reported!

They are not calling it "cure" just an avenue of research that is being pursued. It has shown dramatic results. Finally,...

The therapy was developed by Ionis Pharmaceuticals, which said the drug had "substantially exceeded" expectations, and the licence has now been sold to Roche.

(same source)

After that excitement we hit the Big Pharma wall yet again!

The hope is that other diseases that a similar or have similar attack vectors (bad gene coding), could also benefit from this approach.

The Search seems a bit wonky so here is the other thread on HD reversal. ATS, News, 2/2012 - McMaster researchers reverse Huntington's disease in mice.

In the other thread, a lipid is injected into the brain that slows the disease. Since it is mRNA transcribing DNA that is the actual cause I'm not sure that was a viable road of research. That research was from Canada so is slightly different.

Anything that helps prevent/slow down/and, maybe one day, cure/ Huntington's Disease is thread worthy!

Thoughts?

Sorry that the only source is the Beebs. The research has not been published, yet. Open discussion as I've had browser issues lately...

ETA a bit more info:

They created a snippet of synthetic DNA that messes with the messenger RNA responsible for translating DNA protein codes, effectively blocking the problematic huntingtin protein from every being made. The treatment is called Ionis-HTTRx and made by Ionis Pharmaceuticals, the Guardian reports

Quartz.com - A breakthrough study could lead to synthetic DNA therapies for incurable genetic diseases.

a reply to: TEOTWAWKIAIFF

my thoughts are it's awesome.
huntingtons is up there with ALS as some of the worst # ever.

does it skip a generation usually?
i think i read that somewhere

woody guthrie had huntingtons

This is some fantastic news.

I have a protein issue that I take Humira for. Biologics are a godsend.

a reply to: TinySickTears

If they can narrow down what proteins are involved they can find the source. In this case it is synthetic DNA snippet that wipes out the bad mRNA in the brain/spinal fluid reducing the overall amount of sick cells. The body does the clean up after that!

Most auto-immune diseases are not fun. Either to have or watch others suffer through. You feel so helpless as their own body turns on them.

As far as Wikipedia said, it accelerates in following generations. First shows up in the 50s, next gen, 40s' etc.

a reply to: bigfatfurrytexan

With all the news about CRISPER and zombie apocalypses it is good to hear some real, feel good, positive DNA research news for once!

I found some info on the trial!

The trial enrolled 46 patients with early Huntington's disease at nine study centers in the United Kingdom, Germany, and Canada. Each patient received four doses of Ionis-HTTRx or placebo, given by injection into the spinal fluid. According to the ascending-dose trial design, the dose of Ionis-HTTRx was increased several times during the trial.

Treatment with Ionis-HTTRx led to significant, dose-dependent reductions in mHTT — the first time the protein known to cause Huntington's disease has been lowered in the nervous system of patients.

The drug was safe and well tolerated, as judged by an independent safety committee, which "supports continued development," Ionis said in a news release.

Medscape.com - New Drug a 'Ground-Breaking' Advance in Huntington's Disease.

Acronym soup time!

HTT - Huntington Transcription protein (the good one. It helps neurons communicate and grow in early life)
mHTT - mutant HTT (the bad one, causes Huntington's disease, HD).
Ionis-HTTRx - Company name, HTT (same as above), Rx (prescription), or, company drug!

That it worked is good news. That it worked in proportion to dosage is incredible!

Roche came in because they have financial resources to carry out a larger study. Maybe I'll give them a pass but always have the fear that money, the bottom line, is what is the driving factor.

When all is said and done, prevention would cost less as patients need full time care in the end. That is a huge expense.

Hmmm. I wonder if this is that Deuterium drug they were testing?

I would be skeptical of something being injected into my spine. I suppose the option, Huntingtons, isn't that great though. Maybe worth the risk.

I would think that there should be some dietary modification that could help stop the disease in the first place. Hmmm. first search I did gives a possible cause. en.hdbuzz.net... It would not of thought that milk caused Uric acid levels to go lower in the blood. Now I got something else to study, I wonder how it does that, by blocking blood Ammonia metabolism to uric acid or blocking Ammonia creation in the blood.

Oh sorry OP, got kind of sidetracked, I should refrain from doing side research and posting it. But if I type it, then I can more easily memorize the info.

a reply to: rickymouse

Hey, I just got pulled sideways by something "that should only take a minute of my time"... an hour ago!

As far as dietary goes... I saw on the Wikipedia entry CoQ10 does absolutely nothing. It is a genetic disorder so until they can actually correct the code in utero then it looks like the best way is fight fire with fire (DNA).

This went up on phys.org a few hours ago: Major cause of dementia discovered

The common cause being a toxic build up of urea in the brain - leading to neuronal damage characteristic of Alzheimer's and Huntingdon's and possibly, by implication, other dementias.

We already know Huntington's Disease is an illness caused by a faulty gene in our DNA - but until now we didn't understand how that causes brain damage - so we feel this is an important milestone.

The implication is that the condition could be treated (ideally before major brain damage) with a drug that prevents the build up of urea.

Thank goodness. I don't even think I know anyone with the disease personally but what should that matter anyhow, thank the universe for science and intelligent useful people and machines.

-Alee

originally posted by: EvilAxis
This went up on phys.org a few hours ago: Major cause of dementia discovered

The common cause being a toxic build up of urea in the brain - leading to neuronal damage characteristic of Alzheimer's and Huntingdon's and possibly, by implication, other dementias.

We already know Huntington's Disease is an illness caused by a faulty gene in our DNA - but until now we didn't understand how that causes brain damage - so we feel this is an important milestone.

The implication is that the condition could be treated (ideally before major brain damage) with a drug that prevents the build up of urea.

So instead of being excreted in the urine it's being built up in the brain??? Interesting. I didn't know that.

-Alee

I hope this research goes somewhere. Too often I hear about "A" curing/halting "B" and never hearing of it again. It would be nice to see a disease wiped out Polio style, especially a slow killer like this. Thanks for the interesting post.

originally posted by: TEOTWAWKIAIFF
a reply to: rickymouse

Hey, I just got pulled sideways by something "that should only take a minute of my time"... an hour ago!

As far as dietary goes... I saw on the Wikipedia entry CoQ10 does absolutely nothing. It is a genetic disorder so until they can actually correct the code in utero then it looks like the best way is fight fire with fire (DNA).

Sometimes people's metabolism does not make enough Q10. It can use it once it is added to the diet in a form it can absorb. Those people can get help by taking the supplement. A person who can make it, maybe seventy percent of people will get no help from subsidizing it with pills. But certain meds like Statins, interfere with the making of it so these people who would usually not need it now need it. Statins interupt a cycle which will lower Q10 levels. Some foods have a similar effect, blocking the lipids action. Q10 is a lipid or fat based product. Only a tiny percent of people have a genetic disorder in which Q10 is not useful, both in the body and in supplements. Those people do not benefit from Q10 unless the enzymes are restored that makes it work right.

You see, there are many ways that our enzymes and the genetic snps or gensets can upset things. I personally get a sick feeling from taking Q10, I swell up. I tried it three seperate times years ago when my mother was alive and trying to convince me that I needed it. My brother had the same problem. Evidently from my research I make enough of it and it works properly. So, I get overloaded with it since I do not break down this lipids like testosterone and estrogen and androgen. It requires the same system of enzymes to break it down. I don't make much testosterone, but never had problems because I also do not break it down. My genetics gene apps clearly show this, and I know it is correct because a doctor put me on testosterone shots and I blew up like a balloon. I used them for four months and started to get some bad side effects so I quit. She was a pill pusher, if your testosterone levels are not low, a doctor should not be prescribing shots. The first month I felt pretty good but it was downhill after that. Never again. Only my one daughter and I have the homozygous genset that is a problem. Her kids are heterozygous, no problem, my other daughter and wife and exwife and son in law are heterozygous, so is my granddaughters husband. So unless you have the homozygous form the enzyme works properly, with the mutations the enzyme doesn't work at all. But both my daughter and I have other epigenetics that protect us from getting problems, we do not make much of these hormones.

There are gene corrections that can help normalize a lot of things that they have found to be bad genes. In our case, my one daughter and I cannot take hormone replacement therapy. And we cannot eat much foods that stimulate the creation of hormones. Like Soy products and a few more various foods. We can eat a little, but not too much.

I'll spend eight hours sometimes on a dead end trail doing research, I used to think it was wasted time, but no knowledge is wasted. It gave me the ability to look in many directions and to understand there is more than one possible solution. I have a general idea in which direction I should look from that research in the wrong direction, misdiagnoses are very common by doctors, maybe they should chase their tail more. When you start getting a lot of knowledge, it can effect how you comprehend things. You see what you know or believe and that is not always the right way. I on the other hand have no degrees and a lot of knowledge in multiple directions. I know I know nothing as far as particulars but know which possible directions to research in when someone asks me what may be wrong with them. I also have studied the method of action of meds, I am disappointed, the Pharma companies could tell us how to change our diet based on symptoms, they just sell us pills to make up for the improper enzymes being made or sell us meds to correct something that coffee with caffeine could correct.

The worst thing is most people working at those places doing testing do not have a clue until they get older and pay attention to all of what they were testing. They have disclosure agreements, they cannot tell anyone or risk losing everything.

Here is my question... can they cure the disease with just one injection?

Big pharma doesn't work that way... my guess is that the injections will be a life long thing; thousands of dollars per month, for life.

I have M.S., so I get it. The past few years have been very difficult, and I fear that my M.S. has transitioned to the more aggressive form of the disease.

I wish that there was a cure; the therapy has often been worse than the disease... I would hate having to spend thousands of dollars a month for temporary relief. It makes no damned sense.

If big pharma were to actually cure a disease with one treatment, they would lose millions. That is truth.

a reply to: madmac5150

From studying the actions of medicines I see a lot of side effects where the resulting problem is worse than the disease you are treating. Some of these problems won't show up for a couple of years or more. Big Pharma loves science like this, in five years the drug will probably be banned because of unforeseen major side effects. A lot of meds are silently taken off the market and a law suit cannot be brought because there was no evidence to show the side effects were a future problem.

Only if the company knows there was problems can they be sued, that is why they only test certain things they are required to test for.

My belief with this is that they do not know enough yet to actually know what side effects will occur. A mouse does not live long, how can they tell if it will work long term without any side effects. Maybe in twenty years when they understand the genome better, this would be something that might be feasible. I do not like being a guinney pig myself.

Trying to find a way to keep the genetic trait from expressing itself would be better. If someone wants to try it, I can say they have a right to try it at their own risk. After all, they will not be having good quality of life with Huntington's disease anyway.

a reply to: madmac5150

I was gonna answer rickeymouse but... dude!!

I am so sorry! The story reads that the same approach can help other autoimmune diseases that are genetic. And if they can narrow the source to the genes screwing with your amino acids and/or protein transcription then they can fix you!

The same approach can solve the same problem!

I hope it is true! Like I said autoimmune diseases are not good. Even something as benign as rheumatoid arthritis. And I don’t want to get your hopes too far up, it was small study that needs follow up and real science behind it...

But it is hope! Versus the certain wasting away death... a good thing!

I hope it works out for you too!! There is a shortage of good souls in this world! T’would be a shame to let yours go to waste!

originally posted by: madmac5150
Here is my question... can they cure the disease with just one injection?

Big pharma doesn't work that way... my guess is that the injections will be a life long thing; thousands of dollars per month, for life.

I have M.S., so I get it. The past few years have been very difficult, and I fear that my M.S. has transitioned to the more aggressive form of the disease.

I wish that there was a cure; the therapy has often been worse than the disease... I would hate having to spend thousands of dollars a month for temporary relief. It makes no damned sense.

If big pharma were to actually cure a disease with one treatment, they would lose millions. That is truth.

it wont cure it. In order to cure it, the faulty DNA segment should be replaced with a healthy one. This only works on the result of the faulty DNA, the mRNA. So yes, you would need repetitive shots