[HN Gopher] What can medicine do for people with genes for ALS?
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What can medicine do for people with genes for ALS?
Author : swid
Score : 61 points
Date : 2023-09-21 14:14 UTC (8 hours ago)
(HTM) web link (www.statnews.com)
(TXT) w3m dump (www.statnews.com)
| jddj wrote:
| 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.
| A_D_E_P_T wrote:
| > Morbidly, I guess for me it might be a race between that and
| the cancers that killed off the other side of the family.
|
| <=10% of ALS is inherited. And even if you carry a gene which
| makes you more susceptible to ALS, the risk seems to cap out at
| ~50%. So, at worst, it's a coin flip.
|
| So. It's not an inevitability -- not certain doom. It's a roll
| of the dice, with the odds in your favor.
| jddj wrote:
| That's true, and if I were a gambling man I'd probably back
| the various cancers in that competition anyway, but still
| these things have a way of changing your outlook in subtle
| ways.
|
| That coin-flip-at-worst still probably gives one a better
| than evens chance of falling on the side of the average life
| expectancy where folks don't live to enjoy a long healthy
| retirement, for example.
|
| You might, though, so you can't burn it all either.
|
| There's also some added complexity that comes along for the
| ride when choosing to have children or not, saddled with a
| family history of nasty, fairly early onset baggage.
|
| Another commenter said that embryo selection can help in that
| regard, which is an interesting angle that I hadn't
| considered.
| asveikau wrote:
| The article says that is true for most of the mutations
| causing ALS, but the specific mutation that the subject of
| the story has is more of an inevitability than the other,
| more common ones.
| ToddWBurgess wrote:
| Lost my mother to ALS. She was a nurse so she made a point to
| ask if there was a chance she passed it onto her kids and was
| assured no we are fine. It is a small consolation considering
| all she had to endure.
|
| ALS is a horrible way to exit this earth. It is a death I would
| wish on no one
| bloomingeek wrote:
| Sorry to hear. My aunt died of ALS, so my sister and I
| scheduled some tests with a neurologist for some peace of mind.
| boxfire wrote:
| 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.
| jahnu wrote:
| It's extremely cruel but as you saw people can be resilient.
| The artist TransFatty made a very moving, sad, brilliant, and
| even funny documentary about his experience being diagnosed
| with ALS.
|
| https://m.imdb.com/title/tt4221762/
| busterarm wrote:
| My mom was a nurse who spent a significant portion of her
| career caring for people with neurodegenerative disorders. It's
| a very difficult thing to be in proximity of.
|
| I remember one specific patient that was a child and his
| parents were going to extreme lengths to have him live like a
| normal kid. I forget the specific disease but for the last few
| years of his life he had no functioning nervous system and was
| kept alive by machines until the parents could bring themselves
| to let him go.
|
| I think about these situations a lot and yeah -- it brings out
| a range of strong emotions.
| armadsen wrote:
| 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.
| teeray wrote:
| 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.
| jmyeet wrote:
| 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.
| SoftTalker wrote:
| > Screening fetuses for possible abortion
|
| I don't think we go there. Why is it right to deny someone a
| life just because it's likely to be shorter than average?
| jmyeet wrote:
| Why is it right to give someone a lifelong preventable
| debilitating disease that will drastically reduce the length
| and quality of their life?
| afpx wrote:
| There's an association between ALS and programmers:
|
| See 10.1093/AJE/KWI343
|
| https://sci-hub.se/10.1093/AJE/KWI343
| incongruity wrote:
| 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.
| carbocation wrote:
| 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.
| oidar wrote:
| I really want to like stat news, but it seems like much of
| their journalism style has been informed by celebrity rags. It
| makes it less trustworthy to me.
| armadsen wrote:
| I disagree with you. If the risk is 100% as it is with some
| ALS-causing gene mutations, as well as one that runs in my (in-
| law) family, it's does indeed alone explain risk. At least for
| the disease in my family, timing of onset is relatively
| consistent too (+/- 5 years or something). And maybe more
| importantly, the pathology is such that internal damage is
| happening for years, probably decades, before the first outward
| symptoms appear. If "family member noticed a tiny little
| problem that maybe was nothing, maybe the first symptom of the
| disease, but was concerned enough to go to the doctor" is the
| criteria for diagnosing the disease, and starting treatment,
| that's _way_ , _way_ more subjective and silly than looking for
| a specific gene mutation that causes the underlying pathology.
| beebmam wrote:
| Epigenetics might play a role, too, like it usually does.
| A_D_E_P_T wrote:
| Truth is that we don't even know what [disease] is.
|
| ALS could be several etiologically distinct diseases that
| manifest similarly. And there are indications of this in the
| fact that certain drugs -- like the recently approved Tofersen
| -- have some effect on a subset of ALS cases but have no effect
| on others.
|
| On that note, even Tofersen is of very questionable efficacy:
| https://www.cnbc.com/2023/03/22/fda-advisors-vote-against-ef...
|
| I'm usually hugely sympathetic to "Right to Try" cases. But, in
| the article, you've got people without the disease in question
| (whatever it is) seeking the right to try drugs that are of
| very questionable efficacy to begin with. I say let them have
| it, for whatever good (or harm) it'll do. People can decide for
| themselves whether the side effects they might experience are
| worth the amelioration of fear and glimmer of hope they
| receive.
| NoMoreNicksLeft wrote:
| I know very little about ALS, other than I'm aware that it
| exists and is a nervous system disease. How quick is the
| onset once someone does develop it? Is it a gradual decline,
| a rapid decline, or do they just wake up one morning and
| can't move (falls off a cliff)?
|
| "Right to try" might be worthless in the last case. (Unless
| there's reason to believe that it's reversible with some as-
| of-yet uninvented treatment.)
| SoftTalker wrote:
| It varies. Stephen Hawking lived with it for many years.
| For most people, 2-5 years of steady decline is normal
| between diagnosis and death. In some people it progresses
| more rapidly, in others much more slowly. I don't think we
| really know why.
| margalabargala wrote:
| > in the article, you've got people without the disease in
| question (whatever it is)
|
| Honestly my takeaway from the article, and from a lot of the
| comments here, is that we should be (but aren't) updating our
| definition of "disease" for some diseases as our
| understanding grows.
|
| If you have partially blocked arteries, you're not _actively_
| suffering from heart disease, but it 's normal to give that
| person drugs and advise lifestyle changes as soon as that's
| detected. You don't wait for them to have a heart attack.
|
| Of course, the cause and effect is much better understood
| with heart attacks and isn't at all clear with ALS. But the
| fact that ALS doctors were bewildered that someone might want
| to take prophylactic measures says to me that they have some
| blinders on.
|
| Imagine getting some tests done, learning your coronary
| arteries are 60% blocked and your LDL levels are at the 98th
| percentile, and having a cardiologist tell you "Don't think
| about it for now, come back once your heart stops beating".
| [deleted]
| klipt wrote:
| > ALS could be several etiologically distinct diseases that
| manifest similarly.
|
| What's the common factor - are they all autoimmune diseases?
|
| Would the "inverse vaccine" approach discussed here recently
| help?
| A_D_E_P_T wrote:
| It's unclear whether or not ALS (any form) is an autoimmune
| disease.
|
| Autoimmune diseases are typically associated with
| autoantibody production. These are in evidence in (-- at
| least some forms of --) ALS, but in an unusual way that
| makes their role highly uncertain. They are potentially
| beneficial. See: https://pubmed.ncbi.nlm.nih.gov/25344935/
| btilly wrote:
| The article is about those with the genetic risk struggling to
| get classified and treated as having the disease.
|
| Calling it "genetic ALS" seems like a fair compromise. They
| didn't say "with ALS". They said "with genetic ALS". Which
| seems like a reasonable shorthand for, "with the genetics that
| evidence shows will lead to ALS".
| swid wrote:
| That's the title I shorted it to and my mistake, the STAT title
| actually says "They carry a gene for ALS but aren't sick."
| [deleted]
| ferfumarma wrote:
| You are simply wrong.
|
| The mutations described in this article are a sufficient
| condition to develop ALS, period.
|
| That means that if you live long enough, you _will_ get ALS.
|
| The fact that there are other, yet-to-be-discovered genes that
| could also cause ALS is irrelevant for the individuals that are
| already positive for the SOD1, for example.
| carbocation wrote:
| I guess you disagree with my point that having a disease is
| different from having the risk allele for it, but I stand by
| that distinction.
|
| I specifically addressed timing of onset being important in
| my original comment, because that matters to the person
| living with the problem.
| ferfumarma wrote:
| I agree: the word "disease" necessarily implies signs or
| symptoms of some kind. But what does that add?
|
| The entire _point_ of the article is that the carriers are
| not symptomatic yet, so where 's the confusion?
| A7C3D5 wrote:
| 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.
| RecycledEle wrote:
| You can always kill yourself.
|
| Codifying medically assisted suicide into law would lead to
| abuses. I recall a case where family members and doctors held
| someone down who was fighting and forced lethal poison down the
| person's throat.
|
| At the very least, we must have mandatory video recording and
| reporting of everything related to an assisted suicide and a
| mandatory life-without-parole sentence for those convicted of
| abusing legal euthanasia. We can not let doctors hold someone
| down and force poison down their throats then only get a few
| years in prison.
|
| This is too much like the abortion debate where babies who
| survived attempted abortions were left to die instead of being
| cared for.
| at_a_remove wrote:
| >You can always kill yourself.
|
| Mostly technically true. Once you're locked in, or paralyzed,
| it becomes quite more difficult.
|
| But right now, _most_ suicide methods that are available live
| in the less pleasant octants of the availability
| /suffering/uncertainty space. We used to have some fairly
| pleasant -- by comparison -- deaths available to us but
| they're getting harder to access, leaving the nasty route
| behind. Coal gas? Gone the way of Plath. Barbiturates? Out-
| moded now, know a vet? It isn't like you can nip down to the
| corner for some laudanum like back in the day.
| widowlark wrote:
| if you have ALS, and are bound to your wheelchair, how do you
| accomplish this?
| gautamcgoel wrote:
| > You can always kill yourself.
|
| This is usually painful and unpleasant, and also difficult
| for people with serious impairments (like ALS, for example).
| Perhaps euthanasia should be legal and perhaps not, but in
| any case the quick and painless death available via injection
| is very different from the death you would experience from
| hanging yourself (for example). There are dignified deaths
| and undignified deaths, and I think we should be clear about
| this distinction.
| JumpCrisscross wrote:
| > _recall a case where family members and doctors held
| someone down who was fighting and forced lethal poison down
| the person 's throat_
|
| Shockingly, this is not a legitimate method of euthanasia. At
| the point that you've defrauded an autopsy to that degree,
| you could just have a doctor shoot them in the head and write
| heart attack on the death certificate.
| polski-g wrote:
| Euthanasia is legal in Oregon.
| [deleted]
| gedy wrote:
| I don't disagree per se, but I don't see why federal right is
| so important. We have US states that allow it, so one can
| relocate to states where people have voted for it if that's
| what they want.
|
| Federal power getting involved could also just as easily block
| it from everyone.
| MisterBastahrd wrote:
| Yeah, because relocating is just SO easy. Just ask all the
| women who are being forced into getting sepsis in their home
| states because abortion providers are afraid to treat them
| until they can prove that they have a life threatening
| illness.
| gedy wrote:
| And to my point, what if this was federally banned
| outright? Having state options is better IMHO than a no-
| compromise federal law one way or other on controversial
| issues.
| patmorgan23 wrote:
| Because the expense of relocating to another state and the
| stress/alienation of moving away from family and friends when
| you already require intense medical care is exactly what's
| needed.
| lotsofpulp wrote:
| > We have US states that allow it, so one can relocate to
| states where people have voted for it if that's what they
| want.
|
| This is not easy for people of limited means, hence a federal
| law enshrining people's civil rights over their own
| existence.
| lend000 wrote:
| My understanding is that doctor assisted suicide is legal under
| certain circumstances in California. My father watched his
| terminally ill friend pass this way, and apparently the person
| needs to be able to drink the poison themselves, which could be
| a problem for someone with a paralyzing disease like ALS.
| Whatever they gave him also didn't look particularly painless.
|
| Even more important would be access to experimental/unapproved
| treatments for people with terminal illnesses. It's mind
| boggling that the government still outlaws dying people from
| trying new drugs to potentially save themselves and advance
| medicine because they might be dangerous.
| jawns wrote:
| 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.
| DawsonBruce wrote:
| I lost my father to Huntington's Disease at a young age, and
| have had to live the 50% inheritance chance reality my entire
| life. I've never been tested for the disease, but I probably
| should be eventually. I really hope I don't have it, and only
| time (or a test) will tell.
| Metacelsus wrote:
| Please get tested before you have kids. If you're a carrier,
| it's possible to avoid passing it to your kids using embryo
| selection.
| jawns wrote:
| Note to anyone who is unfamiliar:
|
| Technically, this approach does not avoid passing the
| genetic mutation to the children you conceive. Each embryo
| still has a 50/50 chance of inheriting it.
|
| Instead, the embryos that have the genetic mutation are
| discarded, and only the embryos without the mutation are
| implanted.
|
| If you believe that directly ending a human life at any
| stage, including embryonic development, is immoral or
| morally problematic, this is probably not an approach you
| would feel comfortable taking.
| siftrics wrote:
| "using embryo selection" makes your point with far fewer
| words.
|
| I don't see how else the word "selection" could be
| interpreted in this context.
| CoastalCoder wrote:
| I read the GP as an (oddly worded) effort to raise
| additional considerations.
| siftrics wrote:
| Fair enough.
| jvm___ wrote:
| Huntington's is horrible.
|
| You die like ALS when your lungs stop working. Before that,
| starting in your 40's to 60's you start getting symptoms of
| schizophrenia and Parkinson's, so loss of motor control and
| delusional thought processes. If you know you have it you'll
| eventually not be able to trust your own judgement.
|
| My wife's grandma and uncle's died of it. Grandma was a lady I
| only met as someone who laid in bed with her eyes open but no
| movement or indication she saw you. She did still like
| applesauce by the end. We didn't know if she was there or just
| locked in.
|
| One Uncle, before he was put in a home was living with his
| girlfriend.
|
| Why are you sitting at the window? George is bringing me my
| money. Who's George? My old boss from 20 years ago. You haven't
| seen him in years, does he know you've moved twice and now live
| above a store in a very small rural town? Don't ask questions!
| He's coming to bring me my money today...
|
| Huntington's is not what you want to get.
|
| There's a family genetic mystery as to how Grandma only got the
| disease. August wedding and a December birth in the 1940's. Who
| was the real father?
| swid wrote:
| https://archive.ph/lEynt
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(page generated 2023-09-21 23:01 UTC)