[fgimenez]

[Note that I work in this field and have co-founded a CNS AAV company]

This isn't the correct takeaway. AAV are one of the most complex drug modalities and carry considerable risk when used incorrectly. This story is tragic and violates pretty much every ethical consideration for a clinician researcher. Especially ones that are treating children of desperate parents.

That said, AAV are one of the most powerful delivery mechanism we have to deliver gene therapies to the brain. Uniqure has shown the first efficiacious treatment of Huntington's disease with intraparenchymal delivery of AAV5, Zolgensma is a brain targeted AAV9 to treat SMA, Kebilidi is an intraparenchymal AAV2 that treats AADC deficiency.

The general approach should be to keep dose as low as possible and minimally expose the periphery. AAV9 at large doses delivered intrathecally without standardized immunosuppression is simply insane.

[vibrio]

I agree with you that AAV is clearly a useful tool but at times the low levels of self discipline and scientific rigor that the field has applied to dosing is disappointing at best and scary at times. This includes use of other vector types such as by bluebirdbio and even the Jesse Gelsinger tragedy. “If a little is good then more is better” is a crazy and lazy way to apply and optimize these technologies.

[refurb]

Zolgensma acts on the peripheral motor neurons not the CNS