A Cure for Alzheimer’s Disease? No, just a long line of late stage treatment failures…

3 months ago
58 in steemstem


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It’s really nice to write about breakthroughs in healthcare, such as my two recent posts on asthma and CAR-T therapy in cancer. There is no doubting the unmet need in both of those areas, and the two treatments both have the potential to be game-changing over the coming years – but from a scientific perspective they represent the best case scenarios and drug development is not always like that…

Alzheimer’s Disease is another condition with huge unmet need, and one in which there have been no significant treatment breakthroughs for many years. A small company called Axovant Sciences recently announced eagerly awaited results from a Phase III trial, and the hope of course was that the results would be positive, resulting in the first new treatment for a long long time

Unfortunately the trial failed, that’s the end of the article and so I can close here, please upvote and resteem

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Only joking, I already have a few paragraphs done and so I thought why not add a few more on Alzheimer’s Disease. Many of us no doubt know someone that suffers from Alzheimer’s, and all of us, if we live long enough, will eventually get it

Background to Alzheimer’s Disease

Alzheimer’s Disease was first described by a German psychiatrist, Alois Alzheimer, in the early 1900s

It is a type of dementia, in fact the most common form of dementia, and leads to problems with memory, cognition and behaviour

It is very common and it is growing – according to the Alzheimer’s Association someone is diagnosed every 66 seconds, more than 5 million Americans are suffering from it today, and more than 16 million Americans are expected to have been diagnosed in 2050. And that’s just the US of A…

And the reason it is growing is because it is typically thought of as a disease of the elderly - the greatest known risk factor is increasing age and the majority of Alzheimer’s patients are over the age of 65 - and the elderly population is growing worldwide

The cruel thing about Alzheimer’s is that it is progressive. Symptoms such as mild memory loss and confusion, which may initially be fairly insidious, and perhaps not even noticed for some time, slowly deteriorate, impacting the patient’s life to a greater and greater degree as the months and years go by. By the late stages of the disease, a patient has typically lost the ability to carry on a conversation or react to the environment around him/her. This change in mental state can be very distressing for the patient and for the patient’s family and carers, and the burden placed on the patient, those around him/her, and on healthcare systems is huge


Source in image

Cause of Alzheimer’s Disease

The classic pathological signs of Alzheimer’s Disease are seen in the brain and comprise extracellular deposition of a protein called beta amyloid and intracellular accumulation of a proten called tau

Beta amyloid deposition leads to the formation of amyloid plaques, while tau accumulation leads to the formation of neurofibrillary tangles, and these two together seem to cause the symptoms seen in Alzheimer's patients


Source

Diagnosis

There are no specific clinical findings in Alzheimer’s Disease. Rather, symptoms as outlined above vary from patient to patient, and a diagnosis is typically made based on a history of progressive dementia over a few years, with the absence of another cause (e.g. a brain tumour)

A definitive diagnosis can only be made by pathological examination of brain tissue – i.e. after death. The brains of demented people contain more amyloid plaques and neurofibrillary tangles, and the severity of dementia correlates with the number and spread of these lesions

Prognosis and Treatment

Alzheimer's is progressive and typically fatal within 5 to 10 years of diagnosis, although patients can live for as long as 20 years after diagnosis. Most patients die due to complications of chronic illness – remember that these patients are usually elderly and so often suffer from multiple other conditions

Alzheimer's currently has no cure, but there are options available to help manage symptoms. These include both drug and non-drug options to treat the cognitive and behavioural changes, help with sleep patterns, and help to treat concomitant disease

Unfortunately, there is current no treatment available which prevents disease progression, and so at best the currently available options only bring about a temporary slowing of symptoms and improvement in quality of life for those with Alzheimer's (and their caregivers)

This is a huge area of focus for researchers, and discovering a cure for Alzheimer’s is one of the Holy Grails of medicine, but Alzheimer’s research is littered with failed drug trials, and the search continues

  • The most recent failure was from a small biotech company called Axovant, who announced that an investigational drug called intepirdine had failed a late stage trial (the Phase III MINDSET trial)
  • Earlier this year, the Pharma giant Merck announced that it was discontinuing an Alzheimer’s trial testing a drug called verubecestat as there was virtually no chance of success
  • Before that, the Pharma giant Lilly decided to stop a trial with the drug solanezumab after concluding that there was no reason to believe it could succeed

The list of failures goes on and on and I could list many more, but equally the search for drugs that can slow disease progression also goes on and on, and eventually such treatments will be discovered and approved. There is also a huge focus on identifying markers of disease that would enable early diagnosis and allow treatments to target the disease in the early stages, before irreversible decline has taken place

It seems that there is a long way to go, but sooner or later we will get there – watch this space!!


Cheers

Holbein81

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57
  ·  3 months ago

You've received a FULL upvote from #TheUnmentionables - a SteemIt community full of members who like to kick ass, take names, and occasionally do it wearing (or forgetting to wear) our unmentionables...



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70
  ·  3 months ago

I am beginning to wonder if Tau would be a better target then A-Beta with regards to druggability. Perhaps the formation of neurofibliary tangles are a more significant contributor to disease progression then is accumulation of the a-beta plaques. The axovant drug was not targeting either, it was trying to stimulate 5-hydroxytryptamine receptors in an attempt to mask symptoms, rather than treat the underlying cause. So its failure is separate from my own concerns... alzheimers is not an easy disease to crack that is for certain.

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58
  ·  3 months ago

Thanks for the comment!

I am no expert, but certainly it seems that the correlation between A-beta and symptoms is weak at best and so there must be a lot more going on.
From what I read a fair amount of research is now focused on combination therapies targeting a number of different pathways - which makes sense in terms of moving things forward, but unfortunately I imagine only in small incremental steps.

But for sure, something is better than nothing and if you learn something from those steps then eventually the right path will show itself...

Cheers

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70
  ·  3 months ago

The correlation between A-beta and symptoms is fantastic, it's why so many have been targeting it. Unfortunately those drugs modulating the plaque formation never seem to have the effecacy that we want, nor do they repeat the results we observe from them in animal models. It's odd. It's amazing just how much money has been poured into Alzheimer's (tens to hundreds of billions at this point) for such little progress to have been made.

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58
  ·  3 months ago

Yeah, sorry, I am confusing myself now trying to do too many things at once - could be early onset Alzheimer's...

Sounds like you know your stuff!! More than I do at least 😁

Thanks for the comments!

Cheers

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70
  ·  3 months ago

And thank you for the great post! Looking forward to what you have to bring to the table in the future :)

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58
  ·  3 months ago

Thanks, will look for something healthcare next week. I try to do min one healthcare and one beer post per week. Beer today naturally...

Cheers

51
  ·  3 months ago

This is one of our lost "wars" for now with life. And until the time we find a cure for 1-2 diseases, there are already more others on the way. New and unstoppable.

Our evolution makes us having new obstacles and unknown problems that put us in a constant research.

It could be the nature way to filter our number or it is just the way it is.

I wonder though, how many bad diseases already have a cure and not being wanted to make available to the large public. And how many of them are fabricated and not made by nature. I think last one is a bad choice by some crazy minds without soul.

Also, there are lot of scientists and people that work hard and maybe dedicate all their life to find a cure to such bad diseases. Some will find a way but others not.

We can just hope that we can have a cure for lot of them in the near future.

And also live a good life till then.

I know also, the scandal around the autism. There are pro and cons regarding more kids having it.
Some said it can be caused by some vaccines people taken in their childhood.

Regarding the scandal with US giving test vaccines to kids is another topic, but i think is more sensible and so damn strange that, if true, some people could do that.

Who knows where the truth lies behind all this information we have.

I just hope i will be sane till the end. And not be a vegetable to my family. It is one of the worst thing that could happen to them.

Best wishes to all

#cof

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58
  ·  3 months ago

Thanks for the detailed comment!

To pick up on a couple of things:

I find it incredibly difficult to believe that researchers are developing and then withholding cures. I understand that this makes great material for conspiracy theorists, but practically I just don't see how it could happen

I don't know much about autism, but consider this. Are we seeing increasing cases of autism because 1) Many more children have autism now, or because 2) We are better at diagnosing and have a lower threshold for diagnosis in our 21st century litigious society. I don't know the answer, it's just a thought

Thanks again for commenting!

Cheers

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51
  ·  3 months ago

Yes, it is difficult to believe things like that. So many people would live if some things were released but maybe kept hidden.

I'm not with conspiracy theory but also not against it.
There are always good reasons and points to believe that unbelievable things can... happen. But because humans greed and obsession to destruction too, they are happening in many areas.

I can't know for sure regarding that, but don't tell me that there are not people responsible for spreading new viruses in some places with testing purposes or just with other bad intentions. And here comes some links to the ones mentioned before, regarding holding secrets to possible cures to current diseases or just putting on hold some researches.

Also yes, we do find more people ill and with almost clear result because of the technology we have.

And i saw if i don't mistake... a video with Jack Ma (founder of Alibaba) and some lady there who said that she fight from 19 years to find solutions to make affordable to all people cheap analyzes to help prevent or finding in early stages curable diseases.

And i think she said that they could give some expensive analyzes at some point at prices like $10... so everyone can have them.

So, there are people that are doing good things.

But i heard other times about companies that didn't want to sustain things like that. Even in my country. Saying that they are not sustainable projects...

Also, it is good to have different opinions. This is the way we can have different approach to things we live and to not falling into one side view which will lead to stopping progression.

Nice to see your posts again buddy

64
  ·  3 months ago

Sad to know that there is no treatment yet for Alzheimer. As the father of an autistic son, I have always prayed for a cure for autism and hopefully it will be in my lifetime.

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58
  ·  3 months ago

I can imagine - still a long way to go in science / healthcare!!

Thanks for commenting

43
  ·  3 months ago

Nice post, thanks for the info. One thing I have pondered for over a year (and I work with a lot of Alzheimer's and Dementia sufferers) is that this is the typical pit of 'correlation vs. causation'. A while back they identified the plaques and tangles and put their fingers firmly on Tau & beta-Amyloids as a source for treatment... however just because they are there, they are not necessarily the cause.
I skimmed though the comments and saw inflammation mentioned, and this is a very important issue. In the last 10 years neuroinflammation and exaggerated/chronic immune responses are surfacing as strong factors in neurodevelopmental disorders.
Add to that the recent discovery of a lymphatic vessel network within the brain that is capable of overcoming the blood-brain barrier, that can allow large proteins in the form of pathogens, allergens and other irritants in the brain and you have a cocktail for a whole new set of discoveries. I am really encouraged by the fact neuroimmunology and the relationship between brain and bowel is starting to be made as well. I think we are facing a layer cake and we have only tucked into the icing on top... It will be many decades before we can say we have really cracked neuropathology.
Upvoted for sure.

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58
  ·  3 months ago

Thanks for the v insightful comment!
I agree that we are very much at the beginning - and I think that applies to biotech in general. I really do believe that the next 20 years will be a golden era and in 2030 or so we will look back in amazement at how little we know right now

Cheers

57
  ·  3 months ago

This disease is probably one of the most heartbreaking affliction. 💔 To forget your loved ones... I can't even think about it. Hope they find a way to slow or reverse it soon.

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58
  ·  3 months ago

Very true. I have been fortunate so far with my relatives. But unfortunately it is only a matter of time, and no cure in sight yet - very difficult trials to conduct - but eventually there will be new treatments

64
  ·  3 months ago

@holbein81 - Thanks for this exhaustive coverage on Alzheimer's. I have seen a relative suffer from it and as you have pointed out, it was sad to see him not recognizing even his own son or wife.
Hope a cure materializes some time soon.
Upvoted

Regards,

@vm2904

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58
  ·  3 months ago

Thanks for the comment! I have been lucky so far with my relatives - sure hope it stays that way

38
  ·  3 months ago

The biggest thing is you have to battle inflammation and provide alternative fuel sources. ALZ brains are very insulin resistant so providing alternative fuel sources like ketones can be a great idea. Dr. Mary Newport is doing a lot of awesome stuff with Alzheimer's and coconut oil!

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58
  ·  3 months ago

Alzheimer's has no cure, so in my view patients should try anything they can get their hands on that they feel helps, proven or not - that's what I would do!

Thanks for commenting

53
  ·  3 months ago

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58
  ·  3 months ago

Thanks for reading, and for the resteem!

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53
  ·  3 months ago

You are most welcome

61
  ·  3 months ago

It's a terrifying disease, but we all won't get it- only about 10% of dementia cases are Alzheimer's related. That's still a huge number of people, however.

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58
  ·  3 months ago

Hey @mountainwashere, thanks for commenting!
Where did you get the 10% number from? I had always thought of Alzheimer's as by far the most common cause of dementia, and numbers I see quote it as causing between 60-80% of cases - e.g. here:

http://www.dementia.com/causes.html
http://www.alz.org/what-is-dementia.asp

No, we won't all get it, but only because we will die of something else first - that's what I mean when I wrote that 'all of us, if we live long enough, will get it'.

And of course the population is ageing year on year due to advances in other areas, which is driving up the number of people who do get it before dying of something else

Cheers

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61
  ·  3 months ago

My numbers might be wrong- can't recall where I saw them. I'll do some doublechecking.

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58
  ·  3 months ago

No drama, don't worry about it

Unfortunately even 1% is way too many...

56
  ·  3 months ago

@holbein81,

Ranging from the first man to the second man. They have all said it all. The outbreak of this disease has made some life devastated. Thank you for sharing this.

I will be forwarding it to my Facebook profile and likes so as to spread it.
@stevenmosoes

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58
  ·  3 months ago

Thanks for the great positive comment!

62
  ·  3 months ago

Its such a nasty disease haVe seen the effects on my Mumand a couple of other relatives I hope a cure is found soon

62
  ·  3 months ago

Cool man! Thanks for sharing

54
  ·  3 months ago

hey /@holbein81,
this is good information, you always update the data to facilitate and analyze. This is a good job.

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58
  ·  3 months ago

Hi @robert31 thanks for the comment, glad you enjoyed reading the post!

47
  ·  3 months ago

happiness and good attitude will be a great way to help

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58
  ·  3 months ago

Thanks for the comment!

True, happiness and a good attitude go a long way in life. Unfortunately if you are diagnosed with Alzheimer's then you'll need a bit more than that to stop the disease from progressing

Cheers

39
  ·  3 months ago

Wow amazing

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58
  ·  3 months ago

Thanks!

54
  ·  3 months ago

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67
  ·  3 months ago

Calling @originalworks :)
img credz: pixabay.com
Nice, you got a 4.8% @minnowbooster upgoat, thanks to @holbein81
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60
  ·  3 months ago

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