24/11/2025
💜 GENE THERAPY FOR RETT SYNDROME
Taysha vs. Neurogene — The Updated, Clear, Accurate Breakdown
A Rett dad’s guide for families trying to make sense of the science.
There’s been a lot of confusion across the Rett community.
Parents keep asking:
👉 Who’s ahead?
👉 Which approach looks stronger?
👉 How do we compare outcomes?
👉 What actually matters right now?
As Alex’s dad — 18 years into this fight — here’s the clearest, most factual explanation based on everything available from 2024–2025 clinical data, FDA interactions, company disclosures, RettEd webinars, and scientific meetings.
💜 1. HOW GENE THERAPY MOVES TOWARD APPROVAL
Every gene therapy — SMA, Duchenne, Batten, Rett — follows the same path:
1️⃣ Preclinical: cell & animal studies
2️⃣ Phase 1/2: safety + early signals
3️⃣ Pivotal trial: the big, registrational FDA-required study
4️⃣ FDA review
5️⃣ Approval (if data supports safety & benefit)
Understanding where each company sits in this process is key.
💜 2. WHERE NEUROGENE (NGN-401) IS TODAY
🟣 Neurogene is one step further in the FDA process.
Verified Facts:
⭐ The FDA already approved Neurogene’s pivotal trial design.
⭐ They are enrolled in the FDA’s START Pilot Program — an accelerated support pathway for gene therapies.
⭐ Their pivotal trial (“EMBOLDEN”) is targeted to begin around late 2025.
⭐ Neurogene has released individual patient-level data, making interpretation easier for families and clinicians.
⭐ Fully enrolled pediatric cohort with long-term follow-up ongoing.
What Makes Neurogene Unique:
🧠 ICV delivery — intracerebroventricular (into the brain’s ventricles)
Not intrathecal
Direct brain-CSF administration
Higher CNS biodistribution potential
🧬 Neuron-selective promoter (NSE / NxCSE)
Limits expression primarily to neurons
Reduces overexpression risk in non-neuronal cells
NOT the same as Taysha’s MiRARE
📊 Largest transparent dataset published so far
Videos
Baseline profiles
Individual-level plots
🟪 FDA engagement already at pivotal-trial level.
Current Status:
Neurogene is ahead in regulatory process, not necessarily outcomes.
They still need to show:
✓ Safety across more patients
✓ Durable benefit
✓ Clear, measurable clinical improvement
But regulatory-wise, they’re closer to the finish line.
💜 3. WHERE TAYSHA (TSHA-102) IS TODAY
🟣 Taysha is still in Phase 1/2 — earlier in the path — but moving quickly.
Verified Facts:
⭐ Taysha has Breakthrough Therapy Designation
⭐ Taysha has RMAT Designation (Regenerative Medicine Advanced Therapy)
⭐ This means the FDA believes early data shows meaningful potential
⭐ More participants and new doses (including adults) are underway globally
⭐ A major data update is expected before the end of 2025
⭐ They have not yet released individual-level data
What Makes Taysha Unique:
🧬 MiRARE (miRNA-Responsive Auto-Regulatory Element)
A self-regulating “gene governor”
Built to prevent MECP2 overexpression cell-by-cell
Not neuron-specific — but auto-adjusts expression dynamically
This is NOT the same as Neurogene’s neuron-selective promoter
🧠 Intrathecal delivery
Into spinal CSF
Lower vector dose
Lower systemic exposure
Safer for liver
🌎 First Rett adults treated with a gene therapy
Canada
UK
Australia
Current Status:
Taysha still needs to:
✓ Finish early-phase dosing
✓ Choose a final recommended dose
✓ Launch a pivotal trial (likely 2026)
✓ Publish detailed participant-level data
They are not “behind” scientifically — just earlier in the formal process.
💜 4. WHO IS AHEAD?
Here’s the honest, accurate answer:
🟣 Neurogene is ahead in the FDA approval process
because the FDA has already approved their pivotal trial design.
🟣 Taysha is earlier in development
still completing Phase 1/2 milestones before entering pivotal.
What this does not mean:
❌ Neurogene is proven better
❌ Taysha is proven worse
❌ One company will “win”
Gene therapy doesn’t work that way.
These approaches use different technologies, different promoters, different safety designs, and different delivery routes.
We cannot compare outcomes yet.
💜 5. WHY YOU CAN’T DIRECTLY COMPARE RESULTS
Even scientists can’t, because of:
🔹 tiny sample sizes
🔹 different baseline severities
🔹 different endpoints
🔹 different caregiver surveys
🔹 different ages
🔹 different biomarkers
🔹 data transparency differences
🔹 natural variability in Rett symptoms
It’s not apples to oranges.
It’s apples to galaxies.
💜 6. NEW 2024–2025 INSIGHTS PARENTS SHOULD KNOW
⭐ Symptoms fluctuate — with or without therapy
Breathing, seizures, GI issues, dystonia, sleep storms — all go up and down.
⭐ Age matters
Teens and adults respond differently due to:
• neuroinflammation
• immune priming
• vector biodistribution
• neuroplasticity
• glial activation
⭐ ICV and Intrathecal are not equal
Both target the CNS, but:
ICV = direct brain ventricle delivery
Intrathecal = spinal CSF delivery
Both have pros and cons.
⭐ No gene therapy perfectly restores MECP2
We’re looking for meaningful improvement, like:
• fewer seizures
• better breathing
• stronger engagement
• improved hand use
• better GI regulation
• more purposeful movement
• improved communication
Not a cure — yet.
⭐ Long-term follow-up (10+ years) is required for both.
💜 7. WHAT WE CAN SAY WITH CONFIDENCE
💜 Both programs are scientifically credible
💜 Both have strong FDA engagement
💜 Both show early promise
💜 Both are moving faster than anything in Rett history
💜 Both could help different subsets of patients
💜 We need both programs to succeed
💜 The field is closer than ever
💜 Families should be hopeful, not divided
These therapies are not competitors.
They are two shots at saving our children’s futures.
💜 8. A DAD’S FINAL WORD
I don’t cheer for logos.
I cheer for children.
I cheer for safety.
I cheer for meaningful outcomes — even tiny ones.
I cheer for every family brave enough to enter a trial.
I cheer for the day Rett Syndrome is something our kids read about, not live through.
We are closer today than we have EVER been.
And we will get there.
Together.
💬 Drop your questions — let’s clear the noise and help each other understand.
