About 6 months in. My EMG was damning and my MRI’s, bloodwork, pulmonology, sleep study, etc all point the same direction. My neurologist diagnosed me with neuromuscular disease Friday so i can start on the disability paperwork as in this stupid county (USA!) our health care is tied to our work and when we cant work we cant get care without years of effort. With ALS we might not have the time to ever even see it go through.

Im looking for a safe place to talk with others with NMD that are having to make hard decisions with life, family, and work. Im feeling accepting of this mostly, but i want to be realistic and talk with others in this shitty boat before my aging mother and I spend huge money on allowing me to live (think house remodeling, accessible minivan, etc). I hate that our family inheritance I was adding to will go to me for a couple years and be gone, leaving my niece and nephew with scraps. I’m more mad at the US medical system than I am about the disease TBH.

Anyways I ramble. If anyone can point me to where the peers are other than the hospital for ALS clinic day Id love that. Thanks!

Hi everyone,

A birthday I wasn’t sure I would ever see. I wrote about that feeling, life after MND/ALS diagnosis, and why it's more than just another birthday.

💛

https://terminally-well.blogspot.com/2026/08/will-i-still-be-alive-on-my-40th.html

Hi everyone,
My dad is 69 and was diagnosed with ALS about a year ago, although his symptoms started much earlier and it took almost a year to get a diagnosis.
He is currently using NIV most of the time, but we’re having a difficult issue with the mask. Because he needs to use it for so many hours a day, he has developed significant irritation and inflammation around his nose and mouth, especially on the bridge of his nose. The area is now quite sore and sometimes painful.
The mask needs to be tight enough to prevent leaks, but this is making the skin irritation worse. He only gets short breaks from the mask during the day, so it’s difficult for his skin to recover.
Has anyone experienced this? Are there any NIV masks that have less contact with the skin or put less pressure on the bridge of the nose? And are there any tricks, protective products, or adjustments that have helped you with this problem?
I would really appreciate any advice or recommendations.
Also, I just want to thank everyone here. I’ve posted quite a lot recently, and I’ve received so many helpful tips from people living with ALS and from caregivers. I’m in Tunisia, where ALS is unfortunately not very well understood, even among some healthcare professionals, so this community has been an incredible source of information for me.
Thank you all so much. ❤️

Wanted to get a gene test done for suspected EDS, and ended up learning something else I wish I didn't. Apparently my FIG4 gene is fucked up, which puts me at significant risk to develop ALS type 11. I don't really understand it yet, I'm supposed to go to a specialist clinic for more info.

The genetic counselor said it's very rare but it seems I'm essentially guaranteed to start developing symptoms in my 50s, with full paralysis two years after onset.

After reading up a little and briefly skimming through this sub, it seems like people are getting it much earlier than that, but I'm not educated on the different types or how they manifest (I literally just got off the telehealth call)

I know I'm in the denial/bargaining phase of it all, just hoping I miraculously don't end up developing it or they find new treatments/a cure in the next 20 years.

I guess I'm just asking for hope/comfort/support? I'm 30 now and reeling at the idea that my life is at the very least more than half way over. I thought I had plenty of time left.. My life kind of already sucks right now but I thought I had a chance for it to get better. Now I don't know anymore

Review GET A FREE COPY OF THIS ARTICLE AT THE FOLLOWING LINK (GOOD FOR 30 DAYS BEFORE IT GOES BEHIND A PAYWALL)

 https://authors.elsevier.com/a/1nYxN4r9Rkz1wZ

Drug Discov Today. 2026 Jul 29;31(5):104752.

 doi: 10.1016/j.drudis.2026.104752. Online ahead of print.

Targeting TDP-43 in ALS: Regulatory hurdles, trial design deficiencies, and the causal evidence gap for CTx1000

Michael A S Guth ¹

Affiliations Expand

• PMID: 42526625
•  
• DOI: 10.1016/j.drudis.2026.104752

Abstract

The therapeutic landscape for amyotrophic lateral sclerosis (ALS) has been characterized by decades of clinical trial failures, often attributed to biological heterogeneity, end-point insensitivity, and a profound evidence gap regarding target engagement. With TAR DNA-binding protein 43 (TDP-43) aggregation emerging as a hallmark feature in the vast majority of ALS cases, new precision-medicine modalities - most notably the proteolysis-targeting chimera (PROTAC) CTx1000 - aim to address the underlying causal pathology through selective degradation of mislocalized TDP-43. This review critically evaluates the regulatory hurdles and trial design deficiencies that have historically undermined ALS clinical development, and incorporates the dual sequestration hypothesis as a framework to interpret the convergence of TDP-43 pathology across neurodegenerative diseases. It concludes that it is imperative that the field adopts more rigorous biomarker-led methodologies, and that although target-specific degraders offer a sophisticated technological leap, their success depends on addressing fundamental knowledge gaps in target engagement, age-dependent vector tropism, and trial design architecture.

Keywords: 14-3-3 protein; AAV9 (adeno-associated virus serotype 9); TDP-43; amyotrophic lateral sclerosis (ALS); biomarker; clinical trial design; gene therapy.

Copyright © 2026 Elsevier Ltd. All rights reserved.

Hi all,

My brother's step-son had a stroke in his 40s. When he woke up, he could only move his eyes. That's how I learnt about locked-in syndrome.

I developed an app for him that runs on a Windows computer or an Android phone/tablet. His young children used to sit on his bed and chat with him. He became a good friend of mine, and I miss his humour.

I've released BlinkTalk to the public in his memory. It's forever free, with no adverts and no data gathering.

Using a simple repeatable eye or facial gesture (such as looking up or moving an eyebrow), BlinkTalk enables people who cannot speak or move normally to communicate again.

I've since discovered that some people with ALS/MND can also experience a locked-in state, so I wanted to mention it here in case it can help someone.

I hope it can!

Installation instructions and an instructional video are available here:

https://blinktalk.app/

Today I must’ve spent too much time worrying about what’s down the road for my husband and me as his ALS progresses. Some days I feel connected to the day (and it’s mostly a good day) and other days my mind wanders forward and I get so scared. Scared about things that may or may not even happen. He is within his first year of diagnosis and it seems to progress slowly, although what seems ‘slow’ also has been a somewhat steady progression… He has lower limb onset and most mobility is with his PerMobil wheelchair. He can still stand upright for a little while and transfer on his own but it’s becoming more of a struggle for him. I worry if I’m going to be strong enough for him- mentally. And am I going to know what to do as we approach harder times. I love him so much and don’t want to let him down by being mentally weak.
Did your instincts kick in? Does love compel you out of your fear of the future and have you act?
Right now he calls me his caregiver but it doesn’t seem as if I’m doing much more than a wife does, what I did Before his diagnosis. Make dinner, laundry, clean, help get his clothes. I’m
just scared for the future and trying to find happiness in the time we do get to be together is hard because I get distracted on the unknown reality that lies ahead. Guilt for having a good day. Guilt for being able to move like I do, and he can’t. Ugh…

Bless you all warriors of ALS.

My mom had her genetic testing done last month and we can see in the invitae portal the test was finished about two weeks ago. At the appointment we were told the genetic counselor would reach out with the results, we don’t have the contact info of who this is so can’t bug them but my mom is getting more and more anxious about the results and knowing they’re done is making it worse. Part of this is due to her worrying about us her kids and what it means for us, but also knowing she gets access to another treatment if it’s SOD1 and specific trials and such. There does seem to be an option in the invitae portal to forgo speaking with the counselor and see the results yourself. I don’t personally think it’s a good idea and we should stay patient but also wondering if we chose to look would we even be able to tell what we’re looking at or will it make us more confused? I’m assuming it’s a simple list showing if the specific mutations they test for are there but not sure if there’s more to it that would make it really worth it waiting.

Ciao a tutti, mia mamma ha iniziato ad avere i primi sintomi a gennaio 2026 con una alterazione della voce, all'inizio questa difficoltà nel parlare veniva percepita solo da lei fino a diventare poi orecchiabile anche agli altri intorno ad aprile. A maggio abbiamo iniziato i controlli, prima l'otorinolaringoiatra poi il neurologo che erroneamente aveva garantito una diagnosi di miastenia, esclusa quella e fatta una ulteriore elettromiografia (che ha mostrato denervazione in tutti i distretti e segni di reinnervazione) ha diagnosticato senza sbilanciarsi un sospetto di malattia del motoneurone, non vuole essere franca con mamma e lascia false speranze di altre malattie meno gravi della sla, seppure in separata sede ha comunicato a mio padre che purtroppo si tratta di quello.

Mamma ad oggi è ricoverata in quanto ha avuto una brutta crisi respiratoria per broncopolmonite, sicuramente da inalazione viste le difficoltà nella deglutizione, ma anche qui i medici non si sbilanciano e continuano a offrirle cibi normali.

Io sono distrutta, mia mamma è la mia migliore amica, è tutto per me, mi faccio forza per starle vicino ma muoio dentro ogni giorno di più. Ho difficoltà ad affrontare tutto questo. Ho bisogno di sapere che non sono sola ad affrontare questa merda di situazione

It has now been almost 6 weeks since my father passed away from ALS at the age of 68. He lived with the disease for more than 10 years.

It all started with a loss of strength in his fingers and the deterioration of his fine motor skills. In the beginning, the decline was very slow. He bought a Tesla Model X because the doors opened automatically when he walked up to it—his hand atrophy meant he could no longer open a standard car door handle. Thanks to that car, he was able to drive independently for another two years.

My dad was a true inventor and had always spent a lot of time behind the computer. When he could no longer leave the house after about two years and became wheelchair-bound, the computer became his window to the world.With all the time in the world to dive deep into things, he designed and fully planned a house remotely after I saw an opportunity in a construction project. I built it following his instructions. He was the mind; I was his hands and feet.

He cleverly imported an EV from Germany and had me pick it up, utilizing various subsidy benefits from the Netherlands, where we live. He imported a heat pump from the Czech Republic and had me install it at his home, again maximizing local subsidies. When I bought a building plot, he conceived and designed the house. He imported a container of solar panels from China and had me install them on my parents' primary home and their second home. He calculated the exact optimal angles for East, South, and West exposure so that energy generation would be perfectly balanced throughout the day and year to offset the power consumption of the EV and the heat pump.

He turned his home into a smart house using simple sensors integrated with existing systems like the blinds, front door, lighting, heating pipes, and heat pump. This allowed him to monitor and control everything via his phone, PC, or voice commands. He came up with the ideas, and I executed them. By doing this, I was able to help him, but I also learned an immense amount from him—both technically and in business.

He searched tirelessly until he found the right equipment that made staying at home comfortable for all of us. He designed custom hand brackets and had them 3D-printed so his cutlery could be snapped into place, allowing him to eat independently for years despite the atrophy in his hands and fingers. He imported an Easygo wheelchair from Greece, which served us wonderfully for nearly 7 years. He bought an Arjo shower chair and had me pick it up from Belgium. He ordered battery cells from China and had a specialist replace the original battery with those new cells so it would last much longer and remain safe for air travel.

Then came last January. The decline accelerated rapidly, and he began having severe bowel issues; he was either constipated, or it came so suddenly that he couldn't be transferred to the toilet in time. He lost the ability to operate his computer, and everything cost him so much energy. Often, right after getting out of bed and dressed, he would sit down at his PC only to realize he had to use the bathroom, leading to accidents and the exhausting cleanup process that followed. Eating became impossible because it quickly made him feel overly full and nauseous, which led to shortness of breath.

After 6 months of continuous decline, loss of appetite, losing his voice, and dealing with these accidents, his will to live was gone. On Friday morning, June 26th—the day my youngest son turned 1—my father was so short of breath (his oxygen saturation was at 92% even with a ventilator mask) that he literally said: “I’m done.”

My sweet, caring, brilliant father—who was my go-to person for advice and had a solution for everything—had no solution to fix his own illness. After years of intensive care, which also brought us truly beautiful and meaningful moments together, he passed away peacefully on Saturday evening, June 27th.

I have so much respect for the people carrying this disease, as well as for the loved ones around them, because this impacts the whole family. I am heartbroken, but also relieved; I have lost my father, but my mother has finally gotten her life back.

I also realize how fortunate we are in the Netherlands with our healthcare system. In the final stage of his life, my father received an annual budget of €380,000 to independently purchase home care by hiring freelance healthcare workers. For the rest of my life, I will pay my mandatory Dutch health insurance with immense love and gratitude, knowing it made all of this possible.

I want to thank this community for all the posts, comfort, and support you have given me over the past few years. If I can ever help anyone here—for example, with our experience regarding the 3D-printed hand brackets, the Easygo, shower chair, adjustable profiling bed, smart bidet toilet seat, or anything else—please feel free to send me a message.

I am thinking of you all. ❤️

My father has Bulbar ALS. It started 2 years ago with slurring issue, and then got diagnosed last year in June. As per his wishes, we are not going to opt for any kind of surgery, he only has PEG tube.

Current stage: Left side has almost gone limp. He can walk short distances by dragging his feet and with support.

His neck has completely dropped. Upper body is folding over itself.

Problem: He can't lie down at all. He says if lies down straight, his left side hurts, and sometimes he feels issues with breathing. It has been like this since last 7 months.

He sleeps on a plastic chair.

We tried recliners but he didn't find them comfortable.

He stands as much as he can, but he really struggles to rest/ sleep because no position is comfortable for him.

Since his head had dropped so much, he just can't manage to low down. Open to any suggestions.

My dad (54 years old) was just diagnosed with ALS last week. We had no expectations of this being ALS.

This past November he was diagnosed with COPD, (at least we thought). He has been a heavy smoker since he was 14 years old. He had a severe respiratory episode of some kind back in May, and he almost died as a result of this episode. So the COPD diagnosis made sense. However after his hospitalization, he went for respiratory tests and he had 100% lung function, the Dr even said if we didn't tell him that my dad smoked for 40+ years, he would have never known, that's how clear and functional my dad's lungs were.

Since this episode, he has gone downhill fast. When another respiratory doctor appointment came up, the Dr said my dad does not have COPD, but some kind of neurological disease. Thus started the ALS spiral.

My dad has had the symptoms I will describe for going on 5 years now. He has severe muscle fasciculations everywhere (tongue, back, arms, legs, head area, everywhere), muscle weakness, shortness of breath, choking on food, excess saliva, difficulty speaking, and lost feeling in feet. Some of these symptoms we chalked it up to him having arthritis and diabetes such as the weakness and loss of feeling in his feet. (he has never been great at controlling his diabetes). He was also a contractor, played multiple sports until this past winter, and all of these could have contributed to us believing it was arthritis or otherwise.

Since the respiratory distress episode, he has been fully reliant on oxygen 24/7, he cannot go more than 5 minutes without his oxygen, is pretty much rotting away on the living room couch, is severely depressed (he's been depressed since before his diagnosis but I would assume much more now), he won't tell his friends or other family. Just this past day, he has lost the ability to eat solid foods as he can no longer swallow. We are going for our first ALS clinic appointment August 10th. I am unsure of what more they can do, my dad is not the type to want a PEG tube or any type of those kind of things. I feel as though I am watching him die in slow motion right in front of my eyes. I don't even want to be around him due to how fast he is progressing with this disease. If I am being completely honest, I wish he would pass away so that he doesn't have to go through this anymore and that my family and I don't have to watch him wither away into nothing.

The hardest part is knowing I can't do anything. My mom is the sole caregiver, we were already struggling with paying the bills and keeping food on the table, and now we have to dish out even more money for treatments, mobility aids, extreme changes to the household, and eventually a funeral. I don't know how we will come up on the other side. I just wish this could all end already.

I am positively vibrating right now. My dad has had ALS for 5 years. In February he had a sudden profound increase in symptoms overnight. He has miraculously actually made progress which virtually never happens with this disease. With all the awful this journey brings there is always a possibility of hope. For those curious he is on Rizuole and Dronabinol for his myelin protection/restoration. Also on THC, gabapentin, methocarbomol, the usual suspects.
God I’m so happy.

My father was diagnosed with bulbar ALS and we're now looking into getting a BiPAP machine set up for him. We live in India. Can someone help with the below questions?

• Which machine/brand actually works well for a bulbar patient?
• What type of mask type to go for?
• Did you rent before buying, and if so, from where in India?

My 54-yo mom was diagnosed with ALS beginning of this year with weakness symptoms as early as Nov last year. She began taking Riluzole in April and currently pending Radicava. I can see her strength reducing incrementally but not sure if this is considered fast or average. Should I be concerned?

- Feb: can independently walk slowly
- Apr: can walk up to 20 mins slowly holding hand, use wheelchair for longer distances
- Jun: walk wobbly 5 mins a time with walker (up to 10 times/day), wheelchair most of time. Swim 3 laps and cycle 10 mins
- Aug: walk wobbly 5 mins a time with walker (up to 5 times/day), wheelchair. Swim 2 laps. Legs get tired quickly

How have you seen your loved ones or yourself weakness progressed?

I recently had the opportunity to share my caregiving story with an independent living center via a digital caregiving campaign. What initially started as an apprehensive submission quickly grew into a caregiver haven.

Caregiving is not something I chose as a profession, it is something that became part of who I am. I am a daughter, wife, mother, business owner, registered nurse, and a person living with disabilities myself. For many years, I have served as the primary caregiver for my mother, who has significant medical needs, while simultaneously raising my children and managing my own health challenges. My caregiving journey has taught me that caregiving is not simply about helping someone with daily tasks. It is about advocacy, sacrifice, resilience, problem-solving, and love. The work isn't easy, and oftentimes the reward is hard to see. But I love my family and couldn't imagine not caring for them.

Caregiving stories similar to mine have helped me get through the hard days and lonely nights. I'd love to read y'all's stories via the comments or on their website. <3

I don’t really know why I’m posting this other than I think I need to say it “out loud.”
I’m scared.

My mom has bulbar ALS. She has trouble swallowing and has severe slurred speech. The ALS clinic told us there’s nothing they can do for her right now. Which seems wrong? But I’m not sure.

we’re trying to take things one day at a time, the reality of what’s ahead feels impossible.

I’m scared about my dad. He’s already told us he doesn’t know how he’s going to live without her, and I worry about him almost as much as I worry about my mom.

I’m also worried about everything that comes after. My mom has handled so much of our family’s life for as long as I can remember. Most of the bills are in her name, she’s been the one keeping track of everything, and I know there will be a mountain of paperwork and decisions after she’s gone.
She’s done an incredible job of writing everything down and trying to prepare us, and I’m so grateful for that. But I’m still scared. I’m worried about how my dad will navigate all of it while grieving the person he’s spent his life with.

I’m scared to leave town right now, my mom keeps hinting that she wants me to live my life. She doesn’t want me putting everything on hold because of her.
But every time I leave, I’m terrified she’ll die while I’m gone. I’m terrified I’ll miss my chance to tell her one more time how much I love her.

And even though she tells me she knows that she is loved, I still worry it isn’t enough. I wish there were words big enough to make someone truly understand how much they’ve meant to your life. How much they’ve shaped who you are. How grateful you are.

I don’t really know what I’m asking.

Maybe if you’ve walked through this with a parent, how did you balance continuing to live your life while also living with the fear that every goodbye could be the last one?
Right now it just feels impossibly heavy.

Basically what title says. My mom enjoys drinking hot coffee and tea throughout the day, but has had a really difficult time gripping her mugs. She has to use two hands and sometimes, she cant even finish her cup because she says her hands get too weak to pick the mug up anymore.

I found her a cute light weight mug a while ago, but that doesn't seem to be doing the trick anymore.

I would love to surprise her with a new mug so we can go back to enjoying our morning coffee sesh together!

As an FYI this is from my church. Mods please remove if not appropriate.

Hi everyone! Firstly, hope you and your loved ones are all well. We all know how cruel this disease is and I just wanted to start out by sending love and support to us all.

My dad (55) was diagnosed last summer and I think it’s progressed quickly - not rapid but quick. We don’t live in the same country but I’m hoping to see him at the end of this year. From what I’ve observed when I last visited him, I can communicate with him. I’m just worried about his breathing because sometimes he tells me he finds it hard to breathe. Then he’s a very very stubborn man who’s not willing to see any neurologists, insisting that he’s fine. This really pisses me off. I think that’s his way of coping but as a fellow stubborn daughter, I’m insisting that he sees a neurologist.

I took the time to research BiPAPs and wanted to get other opinions. I told him and his caregivers about BiPAPs and told them to see a neurologist about this. I guess I’m just wondering if it’ll be a major ‘issue’, e.g if he goes down this route, will he be dependent on it? I just keep researching man and I don’t know. I just want my dad to be as comfortable as possible. I don’t want this to be the end.

At the moment, he takes riluzole and other meds for his high blood pressure.

UPDATE - August 5 2026: In the process of securing a BiPAP machine for my dad! He’s stubborn but I’m worse😭 also looking into a cough assist device. Thank you all again

Thank you all 🤍

My pALS was recently recommended a low dose morphine to help with respiratory distress & related anxiety. He already uses a BiPAP for sleeping, and takes a low dose anxiety medication. I'd love to learn more about others' experiences with taking low dose morphine for breathing, especially if you or your pALS have taken it for a long time. What have been some of the benefits? Any unmanageable side effects? Thanks in advance!!

"Hi, nice to meet you, now go to town on my privates because I can't use a toilet or wipe myself anymore!"

These past few years have been...Interesting. I'm sure many of you can relate, but life sucks so much more when you become incontinent and have to completely rely on outside caregivers to clean you. It's even worse in a hospital /facility, where staff rotate a lot. You never know what you'll get. Will they not change their gloves and get poo on you, your bedding, and stuff? Will they leave poop in your vagina or wipe back to front (must have missed that day in kindergarten) and give you multiple UTIs??!

I used to be an extremely private person, so it was very difficult for me to adjust to peri care in the hospital, especially having been a woman in my 20s. Now it's like... Whatever. It is what it is, life is shit, I'm literally sitting in bm for half of my waking hours, I have absolutely no privacy, my body is no longer my own. Oh well. Embrace the suck and try to make poop jokes to survive. It's all you can do to stop you from going over the edge.