FAQ

I want to join the quest for a cure, how can I help?

If you want to help fund our research, you can donate via PayPal or check. Ask your employer to match. Organize a fundraiser or set up a memorial donation campaign. We are grateful for anything and everything you have the time and energy to do for our cause.

If you want to volunteer for research, join us at PrionRegistry.org so that you can stand up and be counted, and learn about research studies you can enroll in. We and our collaborators at Massachusetts General Hospital are currently running a study of fluid biomarkers in people at risk for prion disease, so if you have a PRNP mutation or think you might, and are willing to make clinical visits and donate spinal fluid and blood, you can learn more and find out how to sign up here. (In-person visits are currently suspended due to COVID-19). Note that this is not a clinical trial and you will not receive a drug by paticipating.

How can I set up a memorial donation drive?

Send people the donate link and/or our mailing address: PO Box 391953, Cambridge, MA 02139. Ask them to write your loved one’s name in the “In honor of” field in PayPal or in the memo line of the check. If you want us to compile a list of memorial donations to share back to you or to send acknowledgments, please contact us.

What research do you support? How will my donation be used?

All of the money we raise through Prion Alliance goes to support our research towards a treatment or cure for prion disease. Some goes directly to support our research operations at the Broad Institute, some goes to support the clinical research study at Massachusetts General Hospital, and some goes to service providers or to collaborators’ labs to support the research they are doing together with us. In terms of high-level research agenda, major focuses over recent years have been:

• Testing drugs to lower prion protein in animal models, to establish “proof of concept” for therapeutic strategies and spur investment in drug development.
• Gathering a cohort of prion disease genetic mutation carriers to donate spinal fluid and blood so that we can develop biomarkers to use in clinical trials of new drugs.
• Leading various studies on the genetics, natural history, and molecular markers of the disease.
• Preparing for clinical trials by launching a patient registry, charting out a clinical development pathway for new drugs, and engaging with scientists at FDA.

Donations to Prion Alliance will support us to continue and expand this research effort. Our entire focus is on getting a safe, effective drug into people as soon as possible. Most federal research grants and other conventional biomedical funding sources are oriented around basic scientific research, rather than the kind of focused, practical efforts that are currently rate-limiting for getting a prion disease drug into trials. Over the past several years, our research has been >80% supported by philanthropy.

A loved one has (or passed away of) suspected prion disease, how can we pursue diagnostic tests (or autopsy)?

In the United States, both diagnostic tests and autopsies for prion disease are performed by the National Prion Disease Pathology Surveillance Center located at Case Western Reserve University in Cleveland, OH. If prion disease is suspected, your neurologist should contact the center accordingly.

How do people get prion disease?

About 85% of cases of prion disease seem to arise spontaneously and are known as sporadic cases. These cases appear randomly distributed over time and over geography, and despite decades of searching, no environmental risk factors have been identified, so scientists’ best guess is that the disease originates from a random protein misfolding event in the brain.

Another 15% of cases are caused by genetic mutations in the PRNP gene. In these cases, the DNA mutation may have arisen spontaneously, or it may have been inherited from a previous generation. The DNA mutation then causes the protein to misfold. There is often, but not always, a family history of the disease. Future generations are at risk of inheriting the DNA mutation. Not all mutations are created equal: some appear to cause a >90% lifetime risk of developing disease, while others are just risk factors that may give a 10% or lower lifetime risk.

While prion disease is most infamous for cases acquired through infection, this is vanishingly rare today, causing well under 1% of cases worldwide.

Is it likely that my loved one’s disease was triggered by a particular exposure event or environmental risk factor? Is it suspicious that they had an acquaintance or neighbor who also died of prion disease?

Most cases of prion disease simply come about randomly. In hindsight, family members often identify what appear to be possible triggering factors, such as a stressful life event; dietary or lifestyle change; a surgery, drug regimen, other medical intervention; or theoretical potential for exposure due to travel history or hunting. Other times, people identify what appear to be coincidental clusters of cases in one area over one period of time. In the vast majority of cases, however, these “clusters” are within the bounds of what is expected based on the prevalence of prion disease, which kills about 1 in every 5,000 people, and the potential triggers or risk factors identified are not actually known routes of transmission for prion disease. Cases acquired through infection appear to be extremely rare today. That said, infection events have occurred in the past, so continued vigilance is merited, and any concerns should be discussed with the surveillance center or CDC. To date, all known clusters within a family have been attributable to genetic mutations in the prion protein gene, so the occurrence of multiple cases in a family may be a reason to pursue genetic testing (see below). We at Prion Alliance are not engaged in prion surveillance and will not be able to advise on the potential origins of your loved one’s disease, beyond the general information provided here.

We know or suspect that our family has a genetic mutation that causes prion disease, how can we get predictive genetic testing for healthy family members at risk?

In the United States, predictive genetic testing for prion disease is performed by the National Prion Disease Pathology Surveillance Center in Cleveland (see above). Many people choose to discuss their interest in testing with a genetic counselor or medical geneticist before proceeding, but the genetic test can be ordered by any physician according to the instructions for physicians posted here. It’s free for people with a close relative confirmed to have a prion disease mutation. It costs $412 otherwise, which may or may not be covered by insurance depending on your plan. You may also incur health care costs associated with the doctor’s visits to have blood drawn and receive counseling.

If your genetic counselor or physician is not especially familiar with genetic prion disease, you may want to refer them to our published genetic counseling primer for prion disease.

I have no known family history of prion disease, but underwent genetic testing either for a different condition or for recreational purposes, and a prion protein variant turned up in my test report. Is it a cause for concern?

The variant M129V (also known as rs1799990 or 20:4680251 A>G) is a very common and benign variant, present in about half of people in the world. M129V has been incorrectly annotated in some databases as causing genetic prion disease, and therefore occasionally turns up in automatically generated genetic test reports. In fact, it does not cause genetic prion disease and is not a cause for concern. There are also many other possible variants in PRNP, ranging from benign to low-risk to high risk. If you are concerned about a different variant, we suggest you contact a genetic counselor to discuss.

A loved one has passed away, and we’d like to donate their tissues to research, how can we proceed?

We are unable to accept direct donations of postmortem tissue in our laboratory. We recommend making brain donations to the National Prion Disease Pathology Surveillance Center, which in turn shares brain samples for research purposes to labs across the country, including ours. If extra spinal fluid has been banked in a freezer and is no longer needed for clinical use, we can sometimes accept shipments directly from the hospital or clinic, please contact us to arrange details.

A loved one has just been diagnosed with prion disease, is there an experimental drug we can receive or a clinical trial we can enroll in?

As of December 21, 2023, a Phase 1 clinical trial of ION717, a drug designed to lower PrP, the protein that causes prion disease, has begun recruiting volunteers. The trial is being run by Ionis Pharmaceuticals. Although we collaborated with Ionis on the experiments that led to this trial, we are not affiliated with Ionis and cannot provide the drug nor speak on their behalf. For information on who is eligible and where and how to enroll, please see the official trial posting: NCT06153966. For information on Ionis’s decision about how to design this trial, please see their community statement.

When will a drug be ready for human clinical trials, approved, or available?

The launch of the first clinical trial of a PrP-lowering drug, designed to target the root cause of prion disease, is a big step forward. However, a clinical trial is still just an experiment; we do not know whether the drug is safe or effective. Indeed, early trials are not even designed to determine whether a drug is effective, only to determine whether the drug is safe enough to proceed to larger trials, and to identify a dose level. Even if successful, reaching approval for a new drug takes years. We hope that other drugs will enter human trials in time, but no other candidates are ready for human testing at this time.

I need advice on navigating the healthcare system, making funeral arrangements, handling loss, or talking to family members about prion disease

We do our best to respond to inquiries, but we are often in the lab and we simply receive more email than we can respond to. Our allies at CJD Foundation are really the folks you want to talk to — they have decades of experience guiding people through exactly these issues and they even operate a hotline Monday through Friday.

Is there a risk that COVID-19 infection will cause prion disease, or that the COVID-19 vaccines will cause prion disease?

No. There is no evidence to suggest, nor any scientific reason to suspect, that there is any association either between the virus or the vaccine, and prion disease. In protein aggregation diseases like prion disease, it is known that “like seeds like,” meaning that misfolded prion protein can make other copies of prion protein misfold, misfolded amyloid beta can make other copies of amyloid beta misfold, and so on. But one protein does not cause a totally different protein to misfold. So the sudden appearance of the COVID spike protein in your body, which happens either when you are infected with the virus or when you receive the vaccine, would not trigger prion protein to misfold. Given the vast amount of scientific literature and news media on COVID, there have inevitably been isolated reports of people developing prion disease shortly after being infected with the virus or shortly after receiving the vaccine. That’s entirely coincidental and entirely expected: there is about one new case of prion disease diagnosed every day in the United States, and well over half the population have either been infected with the virus and/or received the vaccine, so there will certainly happen to be cases where prion disease presents just shortly after infection or after vaccination.

My family has a different disease caused by a different gene, and I want to do what you guys have done for prion disease. Where do I start?

Start everywhere and do everything. Read everything you can read and learn everything you can learn. Talk to scientists and doctors who have worked on the disease, other patients and families who are affected, drug companies who have a technology that could help. Figure out what your disease is lacking. Is it a fundamental scientific knowledge gap? Or a lack of funding? A lack of biobanks and patient data? Try to find the aspect(s) that are both most urgently needed and that you have the passion and capability to contribute to. Unfortunately, and we know the urgency you feel, do not expect change overnight. For us, at least, it took years of re-training before we understood the lay of the land well enough to meaningfully contribute.