This week we are excited to launch a new clinical study at Massachusetts General Hospital to study cerebrospinal fluid in people at risk for genetic prion disease, and controls. To learn more about the study details, and find out if you might be eligible, visit the Prion Alliance study announcement. The below blog post will give more scientific background on the study.


You have thousands of different proteins in your brain, but prion disease is caused by just one bad actor, the prion protein (PrP). Experiments in genetically engineered animals have shown that reducing the amount of PrP the brain produces can dramatically delay or prevent prion disease [Bueler 1993, Bueler 1994, Mallucci 2003, Safar 2005], suggesting that therapies to reduce PrP levels should be effective against prion disease. We’ve also found that some humans have one of their two copies of the PrP gene naturally “knocked out” [Minikel 2016], which suggests that reducing PrP levels should be safe as well.

For these reasons, Sonia and I have come to believe that reducing the amount of prion protein (PrP) that your brain produces is the best therapeutic strategy for preventing, delaying, or treating prion disease. A number of different research groups have worked on approaches to reduce PrP, such as RNA interference [White 2008], antisense oligonucleotides [Nazor Friberg 2012], and small molecules [Karapetyan & Sferrazza 2013, Silber 2014]. But not much work has been done to lay the groundwork for how a clinical trial of such a therapy would be done.

prevention matters

All clinical trials in prion disease to date have been done in symptomatic patients. Pre-symptomatic people who have genetic mutations that cause prion disease have never yet had the chance to participate in a clinical trial. Yet many experimental therapies for prion disease that have been tested in animals have been effective at delaying prion disease if the animals are treated before prion infection, or soon after, but have been ineffective after the onset of symptoms [Doh-ura 2004, Kawasaki 2007, Giles 2015]. So if our only plan for testing an experimental drug in humans is to treat symptomatic patients, we run the risk that we could miss out on a therapy that is ineffective after symptoms but could have added years or decades to the life of pre-symptomatic people with genetic mutations that cause prion disease. To maximize our chances of success, we need to be prepared to also do preventive trials — clinical trials in people who have PrP mutations, but are still healthy today.

Sonia and I have a goal that one day it will be possible to offer pre-symptomatic PrP mutation carriers an opportunity to take an experimental PrP-lowering therapy before they develop any symptoms. In such a clinical trial, it will be critically important to measure whether the therapy actually succeeded in lowering PrP. And therefore, before we get to the stage of having a therapy to test, it’s important to know, will it even be possible to tell whether a therapy succeeded in lowering PrP?

the MGH clinical study

That’s where the new clinical study comes in. To be clear, this study is NOT a clinical trial, and no one will be receiving any drug intended to prevent or treat prion disease. This is just a clinical research study to help establish the biomarkers that will one day make it possible to run a clinical trial in pre-symptomatic people.

Research participants will be asked to come to Boston twice (and there are funds available to help with travel costs) for an overnight stay to donate cerebrospinal fluid (CSF) as well as undergoing a blood draw and some other tests — see the full announcement for details. The clinical team at MGH, led by Dr. Steven Arnold and Dr. Aaron Koenig, will handle the clinical visits, and Sonia and I and our team here at the Broad Institute will analyze the CSF. We’ll compare levels of PrP as well as other markers in cerebrospinal fluid on the first and second visit to determine how stable these levels are over time. Quantifying the stability of PrP levels in cerebrospinal fluid over time will help us to determine how feasible it would be to measure a reduction in PrP levels in a clinical trial, and how large a trial we would need in order to do so.

how can I help?

Visit the study announcement page for details) to learn more about eligibility criteria and how to sign up. Just to be doubly clear, no one will be receiving an experimental drug in this study, and participation in this study is NOT a prerequisite to later participate in a clincial trial with an experimental drug. Your participation will contribute to science and help us prepare for clinical trials down the road, but there is no direct benefit to you for participating in this study, and participation is purely voluntary.

The study is being funded by Prion Alliance, and those who can are encouraged to also consider donating to support our ongoing efforts.