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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
> 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.
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.
There is a word for killing someone against their will. It is murder. You may be surprised to find that murders still happen despite it being illegal pretty much everywhere.
We allow euthanaisa for pets because it is more humane than letting them suffer. For some reason that doesn't apply to people?
Anyway, I am guessing you have not witnessed someone you care about slowly die in agony. The theoretical abuse angle doesn't hold up to that reality.
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.
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?
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.
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.
don't you do embryo selection anyways when you use artificial insemination? then this would just be another test if the embryo is viable, making the moral question be the same that artificial insemination already poses.
> 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.
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.
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.
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
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.
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.
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.
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.
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.
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.
> 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".
I think you are nicely describing the field of preventive medicine. You picked a particularly good example (CAD) because we know that preventive efforts work. Hopefully that will expand to all diseases in time. In the circumstances where we really understand the disease process, is seems much better to prevent symptom onset than to wait to treat after things are so bad that the patient notices them.
What's worrying is that based on what the article describes, it sounds like branches of medicine that aren't used to practicing preventative medicine are resistant to beginning to do so.
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/
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.)
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.
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.
In the liability threshold model for disease, complex traits can certainly have monogenic variants that essentially guarantee that disease will occur. For example, homozygous FH (LDLR) will cause clinical disease onset in infancy or early childhood. But most people with FH don’t have homozygous FH.
In fact, we know that ALS is a complex disease because we know that common genetic variants influence ALS risk, but that doesn’t mean that every monogenic ALS variant is going to have its penetrance and onset modified to the same degree. So by saying that ALS is a complex disease I don't mean to take away from the fact that for some families, their causal variant may have a consistent effect with only minimal variation from the genetic background.
I’m fully supportive of preventive therapy. I think that is the actual future of medicine. And so I am a big fan of the idea of using genetics to identify a population at risk, doing individual biochemistry (or whatever endophenotype people use - perhaps imaging or other measurements) to see if the pathophysiologic process is occurring, and treating to prevent disease.
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".
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.
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.
> The entire point of the article is that the carriers are not symptomatic yet, so where's the confusion?
I don't think there is any confusion. In medicine, the disease begins when the symptoms start. Indeed, it's useful to be able to distinguish being a carrier from having a disease.
A coda that I would add is that as our ability to detect abnormalities expands thanks to improved diagnostics, what we consider to be a sign of disease will evolve.
We can’t translate from DNA to biochemistry for almost any trait except for Lp(a), so I don’t count DNA as being a sign right now. But eventually it could be. That will moot this conversation, because at that point we will all be in agreement.
Before cholesterol testing, the sign for FH was a thick layer of lipid particles visible when blood was drawn. As our diagnostics improved, the sign of hypercholesterolemia has been refined to a quantitative value. And each field is trying to accomplish the same.
> "That means that if you live long enough, you will get ALS."
We don't simply don't know that. There is an incredibly wide spectrum of phenotypes, even for SOD1 mutations (~2 of cases) the life span could be as short as 6 months and as large as 25 years.
There are ~120 gene mutations that are incriminated in what scientists call ALS. Each of them has dozens alleles on average.
In addition there are associations between ALS and dozens of occupations, and exposure to thousands of substances. The scientists tell of multi-step diseases.
You are only right in the sense that we will all die at the end.
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.
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.
There are associations between ALS and dozens of occupations, and exposure to thousands of substances.
There is a difference between the prodomal (causative) event and the consequence: The disease. ALS and probably many other neurodegenerative disease could be caused by many events. The scientists tell of multi-step diseases.
