August 2020 Review: Radical Shift on LDT Policy, First Pan-Cancer Liquid Biopsies, and New Alzheimer’s Test

After a long break, the world's first genomics pundits are back for the season. And they are calm and collected in the face of the strorm on Pennsylvania Ave. We're sixty days from an election. How serious should we be taking politicization of the COVID vaccine, this radical shift on LDTs at the FDA?

We also discuss some regular approvals and on rejection that sent the industry reeling with disappointment. Then it's on to Laura's, Nathan's, and Theral's picks for science of the month.

Welcome back!

Do Long Reads Hold Answers for Alzheimer’s? with Mark Ebbert, Mayo

It’s the kind of plot that makes great science.

There are genes that have been hiding in plain sight, undetected until now. They’ve gone unseen, that is, by short read sequencing. Today’s guest and his colleagues call them “camouflage genes,” and a couple in particular may play functional roles in Alzheimer’s disease.

Mark Ebbert is an Assistant Professor of Neuroscience at the Mayo Clinic where he is using long read sequencing technology and computational biology to study neurodegenerative diseases, including Alzheimer’s and ALS.

“For years, the field has know that there are regions of the genome that remain dark when you are using short read sequencing data,” says Mark. "But up until recently, there had been little work characterizing how big the problem was. And as we were working on some studies on Alzheimer’s disease and ALS, we started to bump up to some genes that completely surprised me that they were dark, or what we now call camouflaged. It turns out that 26% of CR1 is camouflaged. I’ve been in Alzheimer’s research for seven years now, and in all that time I hadn’t noticed, and I’ve never heard anyone else mention that CR1 is camouflaged.”

Which leads us to ask, again, why wouldn’t all scientists doing discovery work use long read sequencing? What is the cost of missing an important gene?

Reassessing Alzheimer’s with Larry Goldstein, UCSD

There are drug trial failures. And there are drug trial failures.

The recent move by drug giant Biogen to halt their Alzheimer’s drug has not only been a setback for the company—their stock fell precipitously on the news—it’s also been a major setback for the whole research community focused on this disease. The Biogen trial was one of the last of the major drug companies with high hopes for a significant therapeutic step forward for the neurodegenerative disease. The last five years has seen one big pharma players after another throw in the towel.

Larry Goldstein joins us today to look at the field and give his assessment. He’s been studying Alzheimer’s at his lab at UC San Diego for a number of years. His number one takeaway? Let’s move on from all eggs in the amyloid hypothesis basket—something he did years ago.

Have we made any progress in ten years? Are there any cool new tools on the bench? And have we improved diagnoses at least?