Dear supporters,

It’s with immense gratitude that we announce, once again, a matching campaign: two donors have stepped up to match your donation 1:1 up to a target of $100,000 through August 31. After 14 years on this quest, we are now a clinical stage drug development lab, and your donations will go primarily towards clinical-stage work. That is to say, supporting studies to learn more about prion disease, and what we can do about it, in the species we care most about: humans.

In April we announced that PRiSM, our first-in-human clinical trial of a PrP-lowering divalent siRNA for prion disease, is now launched and recruiting. For more information or to inquire about enrolling, please visit the officical ClinicalTrials.gov entry: NCT07444580. For the moment, we are only recruiting symptomatic patients already diagnosed with active disease (to the pre-symptomatic, at-risk community: please stay tuned). The trial is generously supported by the National Institutes of Health through the NeuroNEXT program, which not only funds the work, but provides a tremendous amount of operations infrastructure to make the trial function. Your donations to Prion Alliance also have a critical role, of supporting travel costs for participants and their caregivers to get to a trial site. Many people have asked how the trial is going, and we have no official announcement yet, other than to say, it is continuing to recruit as planned. This trial is both a shot on goal to develop this specific drug as a therapy for prion disease, and also, a chance for us as patient-scientists to gather data on how to run a prion disease clinical trial and share it broadly in a way that benefits the whole field and community. We have made a commitment to sharing individual patient data from this trial as well as general learnings — our FDA regulatory documents are already freely available online — in order to enable the yet better potential medicines that we hope are not too far away as technology continues to advance.

Thankfully, we are not the only game in town: Ionis announced in March that it is opening a third arm of PrProfile (NCT06153966), its clinical trial of a PrP-lowering ASO. This trial same enrolled 56 patients into two arms, in 2024. We do not run that trial, and, as is typical for pharmaceutical companies, Ionis has been secretive about many details. The company has not stated what the different arms represent, but I believe that it was most likely a low and a mid dose level in 2024, and a high dose level now in 2026. The company says that there will be no public announcement about the results until 2027.

PrP lowering, both by ASOs and by divalent siRNA, works in prion-infected mice, slowing disease progression and extending survival. Thus, while there are no human data available yet, both of these drug programs represent plausible shots on goal that to the best of our current knowledge, have a meaningful possibility of modifying the disease. This is a first in the history of prion disease drug development.

This is very exciting, and at the same time, we need to acknowledge that it’s also an incredibly hard moment emotionally. For years and years, Sonia and I sent emails to people seeking cures for their loved ones, saying, sorry, there’s nothing. The message was devastating but mercifully simple. Now, the message is both devastating and complicated. That message is as follows. There’s no treatment with human data to show that it is safe and effective. There are things in clinical trials. Your loved one might not qualify, if their disease is too advanced, or for any number of other reasons. Geography might make it impractical or impossible to participate. A spot in either trial might not be available right now, and by the time it is available, your loved one might have progressed too far. To everyone we’ve had to deliver this terrible message to, we’re sorry. We are working as hard as we can to push harder and faster, to get answers sooner, to reach the next stage in time for more people.

Even as clinical trials are underway, there remains a lot of groundwork we need to lay for future clinical trials: both for more advanced phases, and for pre-symptomatic individuals. After a brief hiatus due to funding constraints and the team being busy with trials, our biomarker study of pre-symptomatic individuals at Mass General Hospital is now recruiting again. Thanks to your donations, this study is in its 9th year and data from it have proved incredibly valuable in charting out how trials in at-risk people will work. And we have yet additional observational studies we are funding in both pre-symptomatic and symptomatic people, currently in the planning and approval phases, that we hope to be able to announce soon.

The fact that scientifically grounded therapeutics are now in clinical trials shines a spotlight on the need to find the patients sooner. Finding the numbers we need for trials is not an issue: Ionis has told the patient community that its trial enrolled far more quickly than expected, and we’ve likewise been inundated with people interested in PRiSM. But ultimately we want to help as many people as possible, and there are still a lot of patients out there whose diagnosis comes only very late in the disease. In April, Sonia took this message to the annual meeting of the American Academy of Neurology, urging practitioners to accelerate diagnosis of prion disease. We followed this up with a podcast for the neurology community. Later this month, Sonia will travel to the Association for Diagnostics & Laboratory Medicine conference to make a case for how to accelerate the diagnostic pipeline and obtain results faster.

As Sonia always says, this is a race to the first drug and a race to the best drug. So even while our clinical trial is ongoing, our lab is a hive of activity, with our whole team racing to advance the next drug candidate, and the next, into a clinical stage.

We owe you all a huge thanks to all of you for walking this journey with us.

best,
Eric