Given that AMT-130 is delivered via an intrastriatal AAV vector, what have we learned about optimal dosing, vector distribution, and potential immunogenicity risks that could influence broader clinical use or future gene therapy approaches in Huntington’s disease?

Which patient subpopulations (e.g. by CAG repeat length, disease stage at infusion, baseline cUHDRS) appear to derive the most benefit, and are there any biomarker correlates (e.g. MRI, CSF huntingtin levels) predictive of response or safety?

How do the observed effects of AMT-130 compare with existing or emerging therapies in Huntington’s disease, and where do you envision this gene therapy fitting into standard of care (e.g. combination with symptomatic treatments, timing of intervention)?

are there rumblings amongst the community/experts on what sort of internal decision-making occurred to prompt the FDA's flip flop? 

What were initial impressions when evaluating early results against the sham-surgery arm? If the relative parity in results was attributed to variance (i.e. small sample size, not enough time for symptom progression, etc) - does the three year timeframe from September data still pose similar risks? 

The skepticism on some of the questionnaire based results is fair. What does he think of the NfL measures which the team referenced as a secondary endpoint? 

I'm trying to get a sense of the scale of selection bias in this study. Participation was selected on striatum size -- do we know how many participants were screened out? Would this have been accounted for in any of the matched characteristics?

Can we use the low dose group as a pseudo placebo since they received 1/10 dose? This would be underpowered, but I feel like it is still useful and provides a group that is selected the same way as the high dose group

How would a double-blind trial work in this context? A previous speaker mentioned IRBs required cross-over eligibility at 1 year timeframe. Would imagine most people in placebo group would agree, and hard to recruit otherwise if not given that eligibility? 

You want a double blind trial with a 10 hour sham procedure? That is not going to get past IRB boards

Why did you ask someone to answer these questions who isn't familiar with the study?

How does she feel about the FDA moving the goalpost on Uniqure after agreeing to the external control for trial and now going back on that?

How likely are you to prescribe this drug to your patients based on today's data without a confirmatory trial?

At 12 months, how sensible are cUHDRS and TFC scores?

How much of a hurdle is surgery for most physicians to treat HD? Especially looking at next generation drugs like siRNA.