Not if, when.
Dr. Jeffrey B. Carroll (Allen Institute Brain Health Accelerator) visited our lab today to give a guest lecture: “Searching for the toxic species in Huntington’s disease.” “Ground zero” for everyone working on HD was the discovery of the CAG repeat expansion in a gene then dubbed “IT15”, for interesting transcript 15, now known as huntingtin ( HTT ) [ Huntington’s Disease Collaborative Research…
Dr. Robert Thorne (Denali Therapeutics; University of Minnesota; co-founder of International Brain Barriers Society ) visited our lab today to give us a primer on the blood-brain barrier: “Engineering delivery of antibodies, enzymes, & oligonucleotides to the brain & other body tissues through transferrin receptor targeting: transporting biotherapeutics to the final frontier.” These are my notes.…
This blog post is a call to action. Patients newly diagnosed with prion disease in the U.S. have an opportunity to make a meaningful contribution to research by participating in Brian Appleby’s Teleneurology Assessment Program in CJD , or TAPCJD for short. In this post, I’ll talk about this moment in prion disease research, what we need, and how participating in TAPCJD can help. this moment in the…
We announced today that a first-in-human clinical trial of PrP-siRNA is now enrolling symptomatic participants with prion disease. Patients, families and caregivers can learn more on the study’s ClinicalTrials.gov posting as well as official announcements on the Prion Alliance blog and our Community Statement . People interested in participating in the trial should contact a study site to ask to…
This morning Ionis Pharmaceuticals announced that PrProfile ( NCT06153966 ), their Phase 1/2a trial of ION717, a PrP-lowering antisense oligonucleotide for symptomatic prion disease patients, has re-opened. background If you’re just tuning in now, here’s a bit of background. ION717 is the first PrP-lowering drug ever tested in humans. PrP lowering has a strong scientific foundation , because PrP…
Byron Caughey lecturing at Prion2019 in Edmonton, Alberta. Byron Caughey, a wonderful friend and mentor and a giant of the prion research field, passed away on Sunday. For nearly 40 years at Rocky Mountain Laboratories in Hamilton, Montana, Byron advanced our understanding of what prions are, what prion disease is, how to detect and diagnose it, and how we could eventually treat it. In the 1980s…
Above: change in cUHDRS, the primary endpoint of Uniqure’s Huntington’s disease trial. If you’re anyone who spends time thinking about therapies for genetic diseases of the brain, you’ve recently been inundated with the news about AMT-130 , the first genetically targeted therapy for Huntington’s disease to report positive results in a pivotal clinical trial. This is big and exciting news in the…
Last year I blogged about PRNP in gnomAD v4 , which now contains DNA from 807,192 people, and with it, possibly some new insights about prion biology. One surprise was that there were more protein-truncating variants (PTVs) at the C-terminus of PRNP than we expected. This led me to hypothesize their effects might be position-dependent. This blog post is a deeper dive on that question. background…
Today, an exciting announcement: we have obtained permission from the U.S. Food and Drug Administration (FDA) to begin a first-in-human clinical trial of a divalent siRNA drug candidate for prion disease. We are not ready to dose patients just yet, but clearance from FDA is a big milestone, and opens the possibility of a human trial in the near future. In this blog post, I’ll recount how we got…
At the CJD Foundation conference in summer 2014, one member of an affected family stood up during a Q&A session and asked, apropos nothing in particular from the lecture that had just wrapped, “But what about CRISPR? If we can edit DNA, isn’t that your problem solved?” It was a good question! I loved that someone asked it because it was the elephant in the room. Here’s a hotel conference hall full…