Thread by @antonioregalado

We wrote about what we think is only the second gene therapy ever tried for Alzheimer's disease, and the only such trial currently open. (1/3)

technologyreview.com/s/613001/docto…

(2/3) far as we can tell, the first (and so far only) gene therapy trial in alzheimer delivered Nerve Growth Factor to the front of the brain in 49 patients. did not see any benefit. Report was in JAMA Neurology in 2018 jamanetwork.com/journals/jaman…

(3/7) There are several approved gene therapies for rare disease and for cancer. But none for common disease. Because what gene would you target? Not really clear as theses diseases not "monogenic"

(4/7) No one knows exactly what causes Alzheimer's. Many convinced its beta-amyloid plaques, others say tau tangles

“The approach we took is to ignore all that and think about it from a genetic point of view,” says Ron Crystal of Weill Cornell Medicine

(5/7) what does genetic "epidemiology" say? It says e4 version of the APOE gene makes your risk of getting Alzheimer's REALLY high.

Its truly the mother of all risk factors.

'Twas discovered in 1993 by Allan Roses et al /7at Duke.

Here's that paper.
pnas.org/content/90/5/1…

(6/7) The new Alzheimer gene therapy, to be tested at Weill Cornell, is pretty unusual. They are going to add lower risk APOE2 gene to bodies of people with scary high-risk APOE4.

Hoping to get a "mixed risk" state, as show in the curves below of Alzheimer risk by genotype.

(7/7) If it works (big if), this gene therapy could be given to high risk people in middle age. One could try to slow onset of dementia, so people can pass away from something else other than losing their minds.