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Comment by kurthr | Hacker News Reader

TL;DR

Huntington's is caused by an error in a section of DNA called the huntingtin gene. Normally this contains the instructions for making a protein, called huntingtin, which is vital for brain development. But a genetic error corrupts the protein and turns it into a killer of brain cells. The treatment is designed to silence the gene.

One fear was the injections could have caused fatal meningitis. But the first in-human trial showed the drug was safe, well tolerated by patients and crucially reduced the levels of huntingtin in the brain.

The UCL scientist, who was not involved in the research, says the same approach might be possible in other neurodegenerative diseases that feature the build-up of toxic proteins in the brain. The protein synuclein is implicated in Parkinson's while amyloid and tau seem to have a role in dementias. Off the back of this research, trials are planned using gene-silencing to lower the levels of tau.

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I wish all articles were written like your tldr. The BBC article is atrocious, it reads like a list of bullet points. A single sentence per paragraph, no flow.

They're going after the Daily Mail readers who can cope with a few more syllables in their words.

Here is the Guardian piece on it that reads much better. https://www.theguardian.com/science/2017/dec/11/excitement-a...

I wonder how this genetic error could propagate wide enough for the disease to get a name.

It's clearly maladaptive, isn't it?

Of course, same question could be asked for BRCA.

See my other comment for a possible explanation. There seems to be a link between complex brain development and Chorea Huntington, where a higher number of triplets in the gene leads to higher intelligence or more complex brains, but when the number gets too high the disease develops.

Because it usually only kicks in after childbearing years, until relatively recently there's not been a test for it, so no way to know if you'd pass it onto your children, and in the last 200 years life expectancy has gone past the age at which is kicks in, highlighting it more.

> Because it usually only kicks in after childbearing years

Orphans are not a very good evolutionary tactics. But you definitely have a point otherwise. Had it earlier onset age, it would have no way to propagate.

Historically 30-50 would be often be grandparents or great grandparents which has much less evolutionary pressure. Though they would likely still have underage kids.

Historically those kids would have been working already.

A 50 year old can have great grand kids, and a 3 year old at the same time. Though with a large extended family someone can also probably take over in the case something happens.

Do you still call them "orphans" if they're in their mid to late 20s?

There is something important about the type of mutations that drive Huntington's.

Huntington's is caused by an expanded repeat composed of (CAG)n with n>40 repeats. Due to the instability of repeat regions, new mutations arise in this gene at a relatively high rate. So, even if there were strong selection against expanded repeats the disease would continue to exist. However, as mentioned by others here, strong selection is unlikely due to the late age of onset of the disease. So mutation continues to introduce the disease and selection has been too weak to remove it.

In contrast, BRCA mutations differ from the Huntington mutations. BRCA mutations are single "point" changes in the sequence, known as SNPs, that disrupt the protein function. Novel point mutations are exceptionally rare.

So, unlike with BRCA, when investigating why Huntinton's disease exists, one must consider BOTH mutation and selection.

Huntington's also has an interesting place in the history of genetics, genetic diseases, and heredity.

I wish I could find the excerpt, but the book The Gene talks about the original research and it's an interesting story.

The book is worth reading in general (Siddhartha Mukherjee is a great writer and it's really good).

http://www.simonandschuster.com/books/The-Gene/Siddhartha-Mu...

I don't think it's clearly maladaptive. We age and die because it's adaptive to do so. It's possible we've retained a predilection for developing huntington's because it's energy efficient to have some grandparents die.

I'm not arguing that this is necessarily the case, but it is not clearly maladaptive.

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