from Hacker News

What can medicine do for people with genes for ALS?

by swid on 9/21/23, 2:14 PM with 66 comments

• by swid on 9/21/23, 2:14 PM

  https://archive.ph/lEynt

• by boxfire on 9/21/23, 3:22 PM

  Damn. One of the most powerful experiences of my life was working for someone with ALS. They could only communicate via moving and blinking their eyes slightly as I cued them. This person pivoted their career and was actively researching the disease locking them into their brain.

  One day they played a trick on me (I was basically a human auto complete as I took some graduate courses in their field and I was able to help finish the proposal they were writing). They made a joke in the word document. It made me laugh, and as I was looking in their eye I could see the joy that made. I cried so much that night.

  It really really gets to me. Every time I saw a new eye tracker device or otherwise I would email their spouse. I fuckin hate that disease, but I'm amazed at the human spirit I've seen it reveal.

• by A7C3D5 on 9/21/23, 4:21 PM

  I lost two friends to ALS within the span of a year. Barring huge advances in treating this, which I don't see happening anytime soon, I fully plan to take the easier way out should it ever happen to me. Horrific doesn't even begin to describe it.

  Medically assisted suicide should be a federal right. It's abhorrently shameful that we wouldn't allow a dog to die this way, yet somehow it's acceptable to watch a parent or spouse to go through this with NO HOPE of recovery. It makes me so angry.

• by jawns on 9/21/23, 3:17 PM

  My family has been affected by another devastating disease with a clear genetic marker, Huntington's Disease. If a parent has the genetic mutation that causes the disease, each of their children has a 50 percent chance of inheriting the mutation. Unfortunately, while there has been some work to stave off and lessen symptoms, there is no cure, which makes it a very difficult decision for someone to be tested for the mutation.

  In both of these cases (genetic ALS and genetic HD) I think right now the best we can do is have realistic expectations about what physicians, nurses, aides, and others on a person's care team can do, and also to recognize that there are going to be a lot of questions that don't have great answers yet.

  Ultimately, I expect that the greatest breakthroughs for these diseases will come through researchers who only indirectly work with patients, but I have the utmost respect for front-line health care workers who accompany these patients through a terrible situation.

• by jddj on 9/21/23, 3:36 PM

  I lost a parent to ALS.

  Morbidly, I guess for me it might be a race between that and the cancers that killed off the other side of the family.

  I don't really care to get checked for the gene, but I do have a general idea of what needs to happen once the speech starts to go.

• by apple4ever on 10/1/23, 12:46 AM

  My grandfather had Alzheimers and my mother - his daughter - had FTD. I do fear about what that means for me. I did try a study that tested me for a common FTD gene. My aunt - my mom's sister - did not want to know the results. I did. I wanted to know if whether I'd definitely get it, or if that was still unknown. I understand why she didn't want to know, I for me it cave me a sense of understanding about my future.

  That particular test came back negative, so it was helpful to alleviate some anxiety. There are others ones that I must pay for to check my risk further.

  Through watching them deal with this terrible disease, and knowing others have done so and also still others deal with terrible diseases - I can never understand the desire to stick our heads in the sand and say "welp nothing we can do so lets not even try". It very much reminds me of the Columbia disaster.

  It must be a common human thing, because it happens repeatedly. For me, I will advocate that people like me and especially people who are positive are allowed to do whatever they want with their bodies, if they believe it can help them.

• by incongruity on 9/21/23, 6:17 PM

  We have familial ALS in our family. I lost my grandfather, two aunts, and uncle and a number of more distantly related family members to this disease.

  Thank you for posting this article – I'm lucky - my dad tested negative for the gene that has afflicted our loved ones – but I feel so guilty vs. all of my cousins who still have to face these risks.

  We have the power to enable them and others like them to make their own decisions, to have even a slim bit of hope (or even a slim bit of uncertainty) for the first time since we've recognized that familial ALS was a thing. I can't overstate how big of a deal that is. Agency, even if risky, is so much better than the fear and powerlessness of waiting for the inevitable.

• by teeray on 9/21/23, 4:14 PM

  I don’t want this to come off as “oh, well did you just try gene therapy?” but, I am genuinely curious what prevents us from trying to edit out these problematic mutations under a “right to try” basis.

• by carbocation on 9/21/23, 2:58 PM

  This is an important story and my critique is mundane but I wish the headline were more accurate. You don't have "genetic [disease]" unless you have "[disease]", and I think that STAT News should get that right.

  These individuals have what we think is the genetic risk factor for ALS. ALS is probably a complex disease, in which case a single monogenic variant will not, alone, be enough to explain risk, timing of onset, etc.

• by armadsen on 9/21/23, 7:44 PM

  Dominantly inherited Alzheimer's runs in my wife's family and they've faced some similar experiences to those described in the article. Alzheimer's specialists treating her dad initially dismissed the risk of his kids getting it. The vast majority of AD patients don't have any specific known genetic predisposition for it, and among those that do have genetic risk, the most common is APOE mutations where your risk is increased, but it's by no means a sure thing you'll get the disease. The forms that are dominantly inherited and ~guarantee you'll get the disease are maybe 1% of total cases.

  For that reason, even some Alzheimer's doctors seem inclined to treat people as if the dominantly inherited forms aren't worth worrying about until symptoms start. It took quite a bit of pushback and multiple doctors to find one that would refer him to be tested for a EOFAD (early onset familial Alzheimer's disease) causing gene. And of course, just as anyone in his family could have told you, he came back positive for a known pathogenic mutation with ~100% penetrance.

  His kids, all youngish adults, are now in the process of deciding whether to get tested. But if they come back positive -- outside some clinical trials going on with the new antibody drugs (Lecanemab, Donanemab) -- there's nothing to be done other than wait to get it in your 40s or 50s, decline and die. It's a terrible, terrible position to be in.

• by jmyeet on 9/21/23, 5:24 PM

  I see several issues:

  1. It's just more evidence (as if we needed it) that individual health insurance is a fumdamentally flawed system and we should absolutely not base policy decisions on that terrible premise;

  2. There is a danger on physicians attributing symptoms to a genetic illness. Honestly, I think this might even be a cause of medial misogyny (which is real and well-studied) where doctors simply blame symptoms from woman patients on their reproductive system.

  3. Screening fetuses for possible abortion is another issue. Of course this should only be done with parental consent but there's still a eugenics conversation to be had. I'm all in favor of not subjecting people to a debilitating illness if you don't have to.

• by afpx on 9/21/23, 9:18 PM

  There's an association between ALS and programmers:

  See 10.1093/AJE/KWI343

  https://sci-hub.se/10.1093/AJE/KWI343