Can Gene Editing Eliminate Alzheimer's Disease? - Comments

[Ygggdrasil]

Ygggdrasil submitted a new PF Insights post

Can Gene Editing Eliminate Alzheimer's Disease?

Continue reading the Original PF Insights Post.

 

[Greg Bernhardt]

With most disease, early detection is critical. I believe I watched a TEDtalk where a scientist claimed there were clear physical signs in the brain of early Alzheimer’s disease long before any external signs.

 

[Ygggdrasil]

I agree, early detection is crucial for Alzheimer's, especially because some of the failed clinical trial suggest that the disease is too far advanced to be reversed once patients are showing symptoms. There is research into trying to http://www.nature.com/nm/journal/v20/n4/full/nm.3466.html, but although there has been progress, the test is not yet accurate enough to be useful in guiding treatment. The proposal to prescribe drugs to treat Alzheimer's at an early pre-clinical stage or to attempt to prevent Alzheimer's disease, however, has been met with some controversy.

 

[Jimster41]

Amazing. Clearly a lot of challenges, given embryos are already legally complex, and controversial. However, I would also think that families with high risk of alzheimer's would have the kind of perspective to judge. I was reading sort of fast. Is there currently a means of detecting the genetic markers for alzheimer's risk? Is the only leverage point for intervention at the embryo?

Now I have read the other posts...

 

[gravenewworld]

I keep hearing people in the media talk about fixing errors in the genes for Huntington’s disease or cystic fibrosis in human embryos, but why wouldn’t you instead just screen for embryos without the disease-causing mutations? It is easier and probably far cheaper.

I do see therapeutic potential for genome editing of somatic cells for people with some diseases, especially ones affecting blood cells or other easily transplanted cells. And of course, CRISPR and other genome editing technologies will continue to be very, very useful in the lab to create model organisms and genetically modified cell lines. But for human embryos, I just don’t see a lot of upside to the technology.

 

[Ygggdrasil]

Amazing. Clearly a lot of challenges, given embryos are already legally complex, and controversial. However, I would also think that families with high risk of alzheimer's would have the kind of perspective to judge. I was reading sort of fast. Is there currently a means of detecting the genetic markers for alzheimer's risk? Is the only leverage point for intervention at the embryo?

There are a few genetic markers that have been found to affect one's risk of developing Alzheimer's disease. Probably the best known one is the APOE gene. There are three forms of the gene, ε2, ε3, and ε4. ε3 is the most common form, but it seems that the ε2 form may lowers one's risk and the ε4 form raises one's risk of developing Alzheimer's.

Since any genetic intervention would have to target brain cells, intervention at the embryo stage may be the most practical. Performing brain surgery to do gene therapy to insert a gene that will lower one's risk of Alzheimer's does not seem like a feasible solution. Researchers, however, are taking clues from genetic studies to try and design drugs that may mimick the effects of protective mutations or block the effects of deleterious mutations in order to provide another means to tackling Alzheimer's.

I keep hearing people in the media talk about fixing errors in the genes for Huntington’s disease or cystic fibrosis in human embryos, but why wouldn’t you instead just screen for embryos without the disease-causing mutations? It is easier and probably far cheaper.

I do see therapeutic potential for genome editing of somatic cells for people with some diseases, especially ones affecting blood cells or other easily transplanted cells. And of course, CRISPR and other genome editing technologies will continue to be very, very useful in the lab to create model organisms and genetically modified cell lines. But for human embryos, I just don’t see a lot of upside to the technology.

I agree that, for most genetic disorders, PGD is much easier, safer and cheaper way to ensure an embryo is free from genetic disease (a point which I made in my previous article on https://www.physicsforums.com/insights/dont-fear-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-new-gene-editing-technologies-wont-lead-designer-babies/). Where gene editing has an application is in the introduction of rare protective alleles into embryos to significantly lower disease risk. For example, in this article, I look at a rare mutation (present in ~ 0.5% of Scandinavian people and virtually absent in other populations) that seems to lower one's risk of developing Alzheimer's disease by ~3.5 fold. There's certainly a lot more work that can be done before this rare allele could be introduced into embryos safely and efficiently, but such a therapy could potentially eliminate a large fraction of Alzheimer's cases in the next generation of people.

 

[mfb]

My position is that Alzheimer's could be entirely eliminated by genetic editing.
We know this is true.
There are super agers who live past a century without developing Alzheimer-like pathology.

Gene editing, properly done would eliminate 100% of Alzheimer's dementia.

There are also persons who don't die in a traffic accident, that does not mean gene editing will allow to eliminate traffic deaths.
There is no evidence that the Alzheimer risk could be zero with any genetic code.

Given that there are healthy individuals living today that carry this mutation, it does not seem likely that it causes severe problems, especially not at the 1 in 13 level.

Are we sure about that? Did someone screen the population with this mutation for all potentially problematic health issues? Would a 7% higher risk of getting disease X have been spotted, for all X? What about a 1% higher risk to get diseases A, B, C, D, E, F and G?

 

[mfb]

Genetic markers have been found that help prevent the onset of Alzheimer`s disease.

They just reduce the risk.

The APOE 3b variant that I mentioned had profound effects on lowering Alzheimer risk, up to 90%.

While I would be interested in a source for the claimed 90%, it does not help: your original claim was 100%.

It cannot be assured, though I strongly suspect that CRISPering a set of genes could have a profound effect in reducing risk.

That is a much weaker statement.

 

[Laroxe]

While we are getting increasing evidence that the risk of dementia is influenced by specific genes, the discussion here seems to be based on the idea that we have evolved genes to help us develop dementia and I suspect this isn't the case. We know that certain genes in certain combinations influence risk of all sorts of diseases but presumably these genes have survived selective pressures for a reason. The question really is do we know enough about the processes underpinning dementia and do we know enough about how the products of our genes, often in complex combinations influence our physiology.
The genetics of early onset Alzheimer's is pretty well understood but this is rare and isn't really the same disease as late onset at all. The genetics of late onset is far more muddy with a number of genes identified that influence risk but in an unpredictable way. The APOE gene in general controls the production of lipoprotein's, a major physiological process and the various subtypes have been linked to risks of a variety of diseases including cardiovascular, the fact that there is variation in the level of risk doesn't really help when all the subtypes are common and even in those with 2 type e3 variants that shouldn't have any increased risk, 60% will develop the condition by 80. Some people argue that the only effect of the APOE gene is in when people develop the condition.
I think gene editing has potential but only when we actually understand what we are doing. It may have been possible to eliminate the sickle cell trait, which has a clear single gene origin, carried by up to 50% of the population of some areas in Africa and can cause a lot of problems, doing so, would have probably killed millions, the discovery of its effects on malaria only being discovered later than its identification as a cause of disease.

 

[dlgoff]

Evidence is also emerging for a role of copper-2 found in copper plumbing as perhaps the causative agent of
the current Alzheimer pandemic.

http://www.mdpi.com/2072-6643/7/12/5513/htm

This is shocking to know, yet could be valuable knowledge for the general public IMO.

 

[rootone]

Copper piping has been around for quite a while though.
If it does have some detrimental effect for health that may be so, but it can't explain a sudden pandemic outbreak if that is the case.

 

[Ygggdrasil]

Copper piping has been around for quite a while though.
If it does have some detrimental effect for health that may be so, but it can't explain a sudden pandemic outbreak if that is the case.

I don't know if it's accurate to say that there has been a sudden pandemic outbreak of Alzheimer's disease. First, the main risk factor for Alzheimer's is age, so the prevalence and incidence of the disease depends on the size of the otherwise healthy, elderly population in a society in which doctors could notice symptoms of the disease. Second, diagnostic criteria for many neurological diseases change over time, so increases in incidence of a disease could simply be due to changes in how doctors diagnose the disease. For example, diagnoses of Alzheimer's disease used to be reserved for individuals between the ages of 45 and 65, and it wasn't until 1977 that the term was applied to dementia in individuals over the age of 65 (https://en.wikipedia.org/wiki/Alzheimer's_disease#History).

That said, whether copper contributes to Alzheimer's disease is still controversial. While the review that @Alzoom cites makes a compelling case, there are conflicting reports, for example, this study suggesting that copper could actually prevent amyloid formation. More research is likely required to come to a more solid conclusion. However, the recommendations that Brewer makes in the Nutrients paper (avoid supplement pills containing copper, filter water to remove trace copper, wash fruits and vegetables, and reduce dietary fat and meat intake) are very reasonable suggestions for a healthy lifestyle.

 

[Laroxe]

I think the work on metal toxicity is interesting but really quite unconvincing, it seems to change to another candidate metal every couple of years and in fact many of these metals are very common in the natural environment. Aluminium is I think the 3rd commonest mineral on the planet, is widely present in both plants and animals and appears pretty inert, any discussion on poisonings that does not in some way relate symptoms to dosages is rarely useful and most poisons have well described and specific effects. The vast majority of potent neuro-toxins our neurones are exposed to are actually produced in the brain as products of metabolism. There are just to many theories to make much sense out of but again as someone said the clearest risk factor is age, with virtually everyone over 80 having significant accumulations of amyloid proteins in their brain whether diagnosed or not. I recognise the life expectancy figures don't help much, but it is a fact that populations are ageing, there are more elderly people with risk very clearly associated with age. Interestingly there appears to be a new spanner in the works, most people have perhaps heard that despite al the panics about obesity the actual incidence of heart disease is falling and no one is quite sure why. Well it also seems to be the case that the incidence of Alzhiemer's is developed countries is also falling & again its a bit of a mystery. http://www.cam.ac.uk/research/news/...res-in-the-uk-show-decline-over-past-20-years

 

[jakob.worleycun]

While alzheimers and some ofher forms of dementia can be prevented by the altering of genes, once the damage has been done changing the genes may stop the detrimental expression of said gene from further expression, it will not however reverse damage that has been done.