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Comment by samfriedman | Hacker News Reader

Good overview. Does this mean that the next steps to confirming/expanding these findings would be to reproduce this result in neuron cells, rather than skin cells which were differentiated to neuron cells? What are the next steps required to move further up the evidence chain?

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I'm not entirely sure. It seems, from the paper, that mouse models do not share the same phenotype with humans, so animal tests may not be all that helpful, except for some safety data. I'm not sure they will be able to culture actual human neurons from tissue, as that was only recently accomplished back in 2017.

From the paper itself, this is what the researchers say: "These findings warrant further development of ApoE4 structure correctors and, ultimately, testing in clinical trials." So it looks like they want to move forward clinically.

Sounds like a great time to start a biotech company. Though there will be some competition. Am aware of at least two companies in this space ;)

I'm not so sure it's a great time at all. Most alzheimer's drugs have failed dramatically. vTv Therapeutics is the most recent I think. They had a Phase 3 drug trial end early due to futility, and their stock tanked hard. In one day I think it lost 70% of its value.

As far as I'm aware the majority of failing biotech companies have very broadly targeted Amyloid beta (apparently because they thought it was a good risk tradeoff). A narrow focus on APOE4 could be a wiser strategy. I could even see gene therapy playing a role.

There are a few well funded startups targeting apoe4 and other genetic markers of neurodegen disease. Exciting field

Alzheimer's drugs have not been successful, but in general it is the best time ever to start a biotech company. Returns in biotech VC the last 5 years are better than tech, more IPO and big M&A (three $8-12B startup acq in last 4-6 months) even with 1/5 the funding of software, tons of great science out there, massive amounts of capital ($4B venture funding to startups in Q1)

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