The Plan.

For Dad — and for Dad to read too.
82. Twenty months in. FVC 65%. Still on the bike.
Six things to do this month. The first one is the most important.

Pliny — this site is yours to read, edit, push back on, and tell me where I got it wrong. Gail too. The Austin clinic decides everything; this just helps us all get to better questions faster.

Where we are

He's on the HEALEY screening list at the Austin clinic.

That's the biggest door open. The work now is making the screening visit count: confirming the onset-of-weakness date (the 24-month gate), knowing which regimens he's being screened for, and arriving with records in hand. Step 01 covers the pre-visit prep.

The other priority — equal weight, different domain — is reversing the weight loss. See §4.

What we know

HEALEY screening: on the list at Austin clinic ✓
SOD1 mutation: negative (tofersen / Qalsody is off the table)
To confirm: C9orf72, FUS, TARDBP results from the panel
Phenotype: slow-progressing — biking daily at 20 months is a strong positive
Active gap: not currently on riluzole — Step 03
Active concern: weight loss — §4

01
Make the HEALEY screening visit count.

He's on the screening list — that's the door open. Now: arrive prepared, with the answer to the eligibility question already in hand and the right questions ready to ask. One pre-visit phone call beats discovering an issue in the exam room.

The eligibility variable that decides everything
HEALEY's 24-month limit is from onset of weakness, not from the diagnosis date. ALS is typically diagnosed 9–15 months after the first symptom. Before the screening visit, pin down the exact month — ideally the week — that he first noticed weakness, twitching, slurred speech, foot drop, hand fatigue, or anything else attributable in retrospect. Family text messages, calendar entries, or "remember when X happened?" conversations are useful here. Bring that date in writing.

Pre-visit call (512) 920-0140 Austin ALS Clinic · Dr. Yessar Hussain

Address 4705 Spicewood Springs Rd, Austin, TX 78759
Five questions for the pre-visit call (or in person at screening)
1. Which regimens is he being screened for? Regimen I (NUZ-001) is the newest arm; some sites also enroll into earlier-phase Healey ALS MyMatch sub-studies. Worth asking explicitly.
2. What's the screening visit date, and what tests are required at it? ALSFRS-R, slow vital capacity, blood draws for biomarkers, possibly an LP. Knowing in advance helps him show up well-rested and well-fed.
3. If he qualifies, when does dosing start? The HEALEY platform structure usually puts patients into Master Protocol screening, then ~4 weeks to randomization.
4. Who is the site PI and trial coordinator? Get the coordinator's direct line and email — that's the person to reach for everything from here on.
5. If he's outside the 24-month onset window or doesn't qualify, what does the clinic recommend instead? Many HEALEY sites can route ineligible patients into the SEANOBI or SPG302 expanded access programs. Lock in the backup before screening.
Bring to the screening visit
Onset-of-weakness date (in writing) · prior neurology notes & EMG report · current medication list (riluzole, Radicava, anything else) · genetic test report (if available) · most recent FVC/SVC measurement and the date · current weight and height · primary care contact info.

NCT07410806 HEALEY at MGH 9th-arm launch coverage
02

Confirm what was tested in the genetic panel — bring it to the screening visit.

SOD1 negative is confirmed. Three other genes change the trial menu and may be relevant to HEALEY arm assignment: C9orf72, FUS, TARDBP. ~7% of sporadic ALS carries C9orf72. If he has it, TPN-101 Phase 2 opens. If FUS, jacifusen Phase 3 opens. The Austin clinic will want the full report at screening regardless.

Ask the clinic that ordered the test "Was the panel a single-gene SOD1 test, or a full ALS gene panel? Can we have a copy of the lab report?"

If only SOD1 was tested Order the full panel free via Invitae ALS Identified — clinician-ordered, no charge, includes post-test genetic counseling. Turnaround: ~3 weeks.

ALSA on testing 2023 Consensus guidelines
03
Get him on riluzole. This week.

He's not currently on it. Riluzole is the original ALS drug — FDA-approved 1995, the first ever for the disease — and it's the bedrock of ALS standard of care. Real-world data (PRECISION-ALS 2025) shows ~7 months added median survival; meta-analyses of population studies put the range at 6–19 months. The strongest evidence is that it preserves function, not just adds time at the end. It costs about $30 a month generic and Medicare Part D covers it without prior authorization.

Starting it now does not disqualify him from HEALEY. Most ALS trials require stable background therapy (including riluzole) for at least 30 days before randomization. Starting today actually clears one trial-eligibility gate.

The question to ask
"Why isn't he on riluzole already? Was it offered? Declined? Was there a contraindication we should know about?" The answer matters — both for understanding any quiet liver issue and for trust calibration with the clinic.

Call (512) 920-0140 Austin ALS Clinic — same number as Step 01

Ask for "Riluzole 50 mg twice daily, generic, plus baseline LFT panel before first dose."
The drug, briefly
- Dose: 50 mg, twice a day, 12 hours apart, on an empty stomach (1 hour before or 2 hours after meals — food cuts absorption ~20%).
- Form: Generic tablet. Tiglutik (suspension) and Exservan (dissolving film) exist for swallowing difficulty — not needed yet.
- Common side effects: nausea, fatigue, dizziness, mouth numbness. Mild liver enzyme elevation in ~12%; significant elevation in <3%.
- Monitoring: Baseline AST/ALT before starting; recheck monthly for 3 months, then quarterly. Stop only if >5× upper limit of normal.
- At 82: well within normal use. No dose reduction. Slightly slower clearance — just watch LFTs.
- Stack with Radicava ORS: different mechanism (antioxidant). Real-world data shows 84% reduction in hazard of death versus matched controls. Should be added to the same prescription conversation.
PRECISION-ALS 2025 real-world data Lancet Neurology — riluzole & disease stage LiverTox — monitoring guidance Radicava ORS long-term outcomes
04

Get a pulmonologist consult and start the BiPAP plan now.

FVC 65% means he's in the planning window. The "optimized" NIV protocol — start while FVC ≥80%, use >8 hrs/day, daily MI-E cough assist — has a published median survival of 30.8 months versus far less for late or refused use. We're slightly past the ideal start window, which makes the call more urgent, not less.

Ask the Austin clinic "Can we get a pulmonology referral today, plus an order for an MI-E (cough assist) device? Target BiPAP titration before FVC drops below 60%."

Optimized NIV protocol — 30.8 mo median Multidisciplinary care + NIV
05

Get a registered dietitian on the team — this is now tied for first in priority.

He's losing weight. In ALS this is not a side issue: caloric intake is one of the strongest survival levers we have, and the dose-response is large. See §5 for the full evidence base.

Ask the clinic "He's been losing weight. Can we get a referral to the ALS clinic dietitian — and a baseline indirect-calorimetry or REE estimate?"

Also ask "At what FVC and weight do you typically start the PEG conversation? We want to plan, not improvise." (AAN recommends planning before FVC < 50% — he is at 65%.)

Caloric intake → survival Hypermetabolism in ALS
06

Plug into the trial-finder layer. It's free and it works.

New trials and Expanded Access Programs open continually under ACT for ALS. The right move is to monitor passively rather than re-research from scratch each month.

NEALS Trial Liaison (855) 437-4823 alstrials@neals.org Free 1:1 navigator. Email is the fastest channel.

Synapticure (telehealth) (708) 630-1534 synapticure.com Same-week ALS specialist visit; covered by most insurance; second opinion + trial matching.

ALS TDI Trial Navigator als.net/als-trial-navigator Personalized matching tool; takes 5 minutes to set up.

Trial · Phase 2/3 platform · Local

HEALEY Regimen I — NUZ-001

Oral monepantel. The newest arm of the world's largest perpetual ALS trial. Now offered at the Austin clinic.

NCT: NCT07410806
Drug: Monepantel — oral, originally veterinary anthelmintic, repurposed
Eligibility: Age 18+ · FVC ≥50% · ≤24 months from onset of weakness
Where: Austin ALS Clinic · also at Houston Methodist, UT Southwestern
Status: First patients dosing 2026

Action: Step 01. Call (512) 920-0140.

Expanded Access · NIH-funded · For non-trial patients

SEANOBI EAP — MN-166 (ibudilast)

Designed exactly for patients who don't fit a randomized trial. Oral, anti-neuroinflammatory. ~$22M NIH/NINDS-funded under ACT for ALS.

NCT: NCT06743776
Sites: 12 active in US · ask Austin clinic if Texas site is on the list
Status: ~100 / 200 enrolled (Jan 2026)
Best for: Backup if HEALEY window has closed

Action: Have the Austin clinic submit interest. Or contact MediciNova/WideTrial directly.

Expanded Access · FDA-authorized · Synaptic regeneration

SPG302 EAP — Spinogenix

Once-daily oral. First "synaptic regenerative" therapy in ALS. Phase 2: 82% of treated patients had stable or improved progression rates and improved EEG.

NCT: NCT07088159
Program size: 200 patients
Mechanism: Targets cognitive, respiratory, and motor decline together
Best for: Stackable with HEALEY pre-screen / second option

Action: Mention to Austin clinic alongside SEANOBI; ask for the Spinogenix EAP referral path.

Phase 3 · NDA submitted April 2026 ✓

CNM-Au8 — Clene

Oral gold-nanocrystal suspension. Statistically significant NfL and GFAP reductions. NDA submitted to the FDA in April 2026 under the accelerated-approval pathway — based on biomarker endpoints plus survival data from >800 patients. If accepted, a PDUFA decision is plausible in H2 2026.

Confirmatory trial: RESTORE-ALS · ~690 patients · 2:1 active:placebo · dosing began H1 2026
Why interesting: Nearest-term ALS approval candidate. Could become a standard-of-care add-on by late 2026.
Best for: Watch list — track FDA filing acceptance and PDUFA date

Action: Watch for FDA acceptance announcement. If approved, ask the Austin clinic about adding it to standard-of-care.

Phase 2 · Treg immunotherapy · NEALS-affiliated

COYA 302 — ALSTARS Trial

Combination of low-dose IL-2 + abatacept biosimilar. Targets the same Treg dysfunction biology Stanley Appel pioneered in Houston. ~25 sites in US/Canada.

NCT: NCT07161999
Enrollment: 120 patients · 2:1 active:placebo over 6 months
Likely Texas site: Houston Methodist (3-hr drive)
Best for: Backup if HEALEY isn't an option; requires travel

Action: Ask Houston Methodist directly: (713) 441-3760.

Phase 3 · Just enrolling · Eligibility flag

PREVAiLS — Pridopidine

Oral sigma-1 receptor agonist (Prilenia / Ferrer). Phase 2 (HEALEY Regimen E) showed ~32% slowing of progression in early-onset patients. First Phase 3 patient enrolled March 30, 2026. 500 patients across ~60 global sites.

NCT: NCT07322003
Eligibility: Symptom onset ≤18 months
Pliny's status: Likely outside the window at ~20 months in. Worth asking Dr. Hussain whether slow-progressor phenotype affects this interpretation.
Best for: Watch only — but if Austin or Houston Methodist is a site, raise it explicitly.

Action: Mention to Dr. Hussain at the screening visit. Ask whether the 18-month onset cutoff has any flexibility for slow progressors.

Riluzole 50 mg, twice daily

The original ALS drug (FDA 1995). Real-world: ~7 months added survival; meta-analyses 6–19. Not currently on it — Step 03 covers how to start.

Radicava ORS (oral edaravone)

Real-world: 84% reduced hazard of death vs matched controls; ~7-month median survival prolongation. Oral form approved 2022; no IV infusions needed.

BiPAP / NIV — optimized protocol

The single largest published survival lever outside of trials. Optimized = start at FVC ≥80%, use >8 hrs/day, daily cough assist. Median 30.8 months vs much less for delayed/refused use.

MI-E cough assist (insufflator-exsufflator)

Bundled with the optimized NIV protocol above. Gets prescribed alongside BiPAP. Prevents respiratory infections — a leading cause of death in ALS.

Multidisciplinary clinic care

AAN Level B evidence for survival benefit. He's at the right kind of clinic already (ALSA/MDA-affiliated). Stay there.

Registered dietitian, ongoing

See §5. Weight is one of the largest survival levers. Recurring touchpoint, not a one-shot.

Physical / occupational therapy

To set guardrails on the cycling and design a non-fatiguing routine. Not to push harder — to keep him from overdoing it.

PEG planning conversation

AAN: plan before FVC < 50% and before >10% body weight loss. He's at FVC 65% — this is a "have the conversation now, decide later" moment. Avoiding it means making the call in crisis.

Keep biking. Stop short of fatigue.

A 2025 systematic review and meta-analysis found moderate, personalized exercise is safe across studies in ALS — no serious adverse events. Aerobic exercise was the most effective intervention for FVC. Resistance training was the most effective intervention for daily function. Seven of eight recent strength-training studies showed positive outcomes.

The only firm rule: don't exercise to soreness or exhaustion. ALS muscles don't recover from overexertion the way healthy ones do. The classical neurology fear that "exercise accelerates ALS" is no longer supported by current evidence — but the principle of submaximal exertion still holds.

Practical guardrail

If he feels fatigue, soreness, or cramping for hours after the ride — that ride was too long. Shorter, flat, daily beats long and hilly.

2025 meta-analysis (Frontiers) Resistance + ALSFRS-R pilot

The weight loss is the alarm bell.

ALS isn't ordinary aging. Patients are hypermetabolic — resting energy expenditure is roughly 22% higher than age-matched controls (~1500 kcal/day vs ~1230). To gain weight, ALS patients have had to consume ~150% of "expected" calories in trials. Most don't, and weight loss is one of the strongest predictors of faster decline.

The dose-response curve nobody talks about

Daily intake	Median survival
< 25 kcal / kg ideal body weight	24 months
25 – 30 kcal / kg IBW	38 months
≥ 30 kcal / kg IBW	63 months

Source: Frontiers in Neurology, 2023 — observational, but the largest published cohort linking caloric intake to survival.

Other findings from the cohort literature: losing >5% of body weight over 6 months is associated with significantly faster decline. Post-diagnostic BMI loss of ≥2 kg/m²/yr is associated with shorter survival. Weight gain after diagnosis appears to improve prognosis.

Hypermetabolism is real and persistent BMI ↔ survival + metabolomics

What to actually feed him.

The evidence is clearer on "how many calories" than on "which kind." The LIPCAL-ALS trial (high-fat 405-kcal capsules added on top) didn't show survival benefit. What worked in observational data is total caloric sufficiency — keeping weight up, by any reasonable means.

Target a number. Estimate his ideal body weight in kg, multiply by 30 — that's the floor. For a 70-kg ideal-body-weight man, that's 2,100 kcal/day. Many ALS patients need closer to 35–40 kcal/kg.
Calorie-dense, not volume-dense. ALS patients fatigue partway through meals. Olive oil, butter, avocado, full-fat dairy, nut butters, eggs, salmon. Add fat to everything.
Frequent small meals + snacks. 5–6/day beats 3 large ones — chewing fatigue is real.
Liquid calories matter. Whole milk, smoothies with banana + nut butter + yogurt + olive oil. Boost / Ensure Plus / Carnation Breakfast are useful between meals, not as substitutes.
Mediterranean base, calorie-loaded. No evidence that ketogenic or strict-Mediterranean help more in ALS specifically. Don't restrict.
Weigh him weekly (same scale, same time of day). Any month-over-month loss is a flag for the dietitian.

The honest framing

"Eat what he likes, in larger amounts, with more fat in it" beats any specific named diet. Pleasure matters; he has to actually eat the food.

Supplements: what to stop spending money on.

The honest summary of the supplement literature in ALS: most have failed when actually tested.

CoQ10: Phase II at 2,700 mg/day was not superior to placebo. No survival or function benefit.
Vitamin E: Mixed; nothing convincing.
Creatine: Equivocal in ALS specifically.
High-fat caloric supplement (LIPCAL-ALS): No survival benefit at 405 kcal/day of pure fat.

What is emerging — but not yet ready for action — is the microbiome literature. 2025 reviews show altered gut microbiota in ALS (Bacteroidetes up, Firmicutes down) and Akkermansia muciniphila slows progression in mouse models. Human RCT data does not yet exist. So: not a reason to spend on probiotics, but a reason to keep an eye on the field.

CoQ10 Phase II — failed LIPCAL-ALS — failed 2025 microbiome review

Home base

Austin ALS Clinic

Director: Dr. Yessar Hussain

4705 Spicewood Springs Rd
Austin, TX 78759

(512) 920-0140

ALSA/MDA-affiliated multidisciplinary clinic. Newly designated HEALEY Platform Trial site. This is the most important phone number on the page.

3-hour drive

Houston Methodist ALS Clinic

Director: Dr. Stanley H. Appel · world-leading Treg-in-ALS researcher

Houston Methodist Hospital · Texas Medical Center

(713) 441-3760

First multidisciplinary ALS clinic in the US. HEALEY site. Likely COYA 302 site. New patients require physician referral and prior medical-records review.

3-hour drive

UT Southwestern Neuromuscular

5303 Harry Hines Blvd, 8th Floor
Dallas, TX 75390

(214) 645-8800

MDA/ALS Care Center Network. Accepting new patients. HEALEY site.

3-hour drive · alt.

Baylor College of Medicine ALS Clinic

Medical Director: Dr. Yadollah Harati

7200 Cambridge, Suite 9A
Houston, TX 77030

(713) 798-2273

Houston alternate to Methodist. Worth knowing for cross-referral or second opinion.

No therapy currently available reverses ALS. The realistic, evidence-backed best case from this plan is meaningful slowing of progression and preservation of the things that make life feel like life — the cycling, eating with the family, holding a fork, breathing without struggle.

The largest survival levers that don't require a trial slot are boring: aggressive nutrition, optimized non-invasive ventilation, multidisciplinary care, the two FDA-approved drugs. Everything in §1–4 stacks on top of those, not in place of them.

The genuinely cutting-edge things that could change the trajectory: HEALEY Regimen I if the onset-date math works; CNM-Au8 if the FDA approves it in late 2026; SPG302 if early signals hold up. The next twelve months will produce real signal on all three.

Speed matters more than perfection. A reasonable phone call made today beats a perfect plan made next month.

The Plan.

Make the HEALEY screening visit count.

Confirm what was tested in the genetic panel — bring it to the screening visit.

Get him on riluzole. This week.

Get a pulmonologist consult and start the BiPAP plan now.

Get a registered dietitian on the team — this is now tied for first in priority.

Plug into the trial-finder layer. It's free and it works.