At the request of Debbie Yobs and Lori Nusbaum, these are my non-technical summaries of the talks at the CJD Foundation’s 2015 Family Conference held in Washington, D.C. on July 10-12, 2015, intended for a general audience.

Byron Caughey

Dr. Caughey’s keynote lecture opened with an overview of what prions are, and how prion diseases develop. Everyone has a protein in their bodies and in their brains called the “cellular prion protein” or PrPC, which normally is a perfectly healthy thing. But if PrPC folds differently and changes its shape, it can then induce other copies of PrPC to change shape too. This alternate, infectious, shape is called PrPSc, it spreads across the brain by a domino effect, converting more and more copies of PrPC as it goes. Once thought to be a totally unique disease mechanism, it is now believed that similar phenomena may underlie Alzheimer and Parkinson diseases.

Dr. Caughey’s recent work has taken advantage of this unique property of prion diseases to develop better tests for diagnosing prion disease. He spent most of his talk introducing a test called “real-time quaking-induced conversion”, or RT-QuIC for short. RT-QuIC basically reproduces the infamous “domino effect” of prion disease in a dish. To prepare purified protein for the test, people have copied the prion protein gene, which contains the DNA instructions for how to make prion protein, into bacteria. They grow the bacteria in the lab and then use biochemical techniques to purify out the prion protein. Next, that protein is mixed with a fluorescent dye called thioflavin T. The mixture is placed into a 96-well plate, which is a plastic plate about the size of your mobile phone, with 96 separate wells in it for performing multiple reactions in parallel. Then, into each well, they add a sample of patient biofluids. If they’re analyzing autopsy samples this might be brain tissue, while if the purpose is to diagnose a living patient, they might use cerebrospinal fluid or nasal brushings. Then they seal the plate and put it into a machine that shakes and heats it. What happens next is the real trick: if and only if there are prions in the patient sample, those prions will cause the purified protein from bacteria to change its shape. The fluorescent dye is a pale yellow normally, but when the protein changes its shape, the dye binds to it and fluoresces much more brightly. Therefore, just by watching the fluorescence in the plate, you can tell whether the patient had prion disease.

This test was only developed a few years ago [Wilham 2010, Atarashi 2011]. Most of Dr. Caughey’s talk discussed improvements to the test that his lab has achieved over just the past two years. They figured out that the test works on nasal brushings, which may offer a less invasive way to diagnose the disease without a spinal tap [Orru 2014]. They also tweaked the reaction conditions to make it run faster, so that now the test can be completed in 24 hours instead of 3 days [Orru 2015]. Finally, they used to produce a lot of different types of prion protein from different species in their bacteria, because some species are better than others at detecting different subtypes of prion disease, but they have now simplified their workflow by discovering that just one type of prion protein - from an obscure rodent called the bank vole - is able to detect every known prion strain [Orru & Groveman 2015].

Dr. Caughey concluded that he is hopeful that RT-QuIC will allow earlier diagnosis of prion disease, making it possible to initiate treatments (once we have any) earlier in the disease course, and to monitor whether the treatments are working.

Glenn Telling

Dr. Telling opened with a review of the different ways that people have studied prions over the years. There are many species that naturally suffer from prion diseases - sheep, goats, deer, and so on. But these species are large, they live a long time, they are very expensive to raise and study, and they suffer from different strains of prion disease than humans do. In the 1960s, Carleton Gajdusek showed that human prion diseases such as CJD could be transmitted to chimpanzees. But chimpanzees are not an easy way to study the disease either. Therefore, Dr. Telling’s early work focused on putting the human prion protein gene into mice, and then showing that those mice could be infected with human CJD and FFI just like Gajdusek’s chimpanzees [Telling 1994, Telling 1995, Telling 1996]. This meant that for the first time there was a tractable way to study human prions in the laboratory. More recently, Dr. Telling has genetically engineered analogous mice that have sheep or deer prion protein, and can be used to study scrapie or chronic wasting disease.

But animals, even mice, take a long time and cost a lot of money. For things like trying to discover drugs to treat prion disease, we need even quicker models, which is why people turn to growing cultured cells in the laboratory. 15 years ago, people discovered that quinacrine, a drug originally used for treating malaria, appears to reduce the growth of mouse prions in mouse cells, which led to clinical trials where quinacrine was used to treat patients with CJD. Dr. Telling’s recent work ahs shown that in cells infected with deer chronic wasting disease prions, quinacrine paradoxically appears to increase the quantity of prions produced [Bian 2014]. This is believed to be because prions come in different “strains” which are differently folded shapes of prion protein, and deer and mice suffer from prions of different strains. This means that it will be hard to predict what will work in humans based on mouse prions or deer prions. Therefore, he concluded, if we want to find a drug for CJD, we need to the most accurate possible model of CJD.

Thomas Wisniewski

Dr. Wisniewski discussed his efforts over the past 15 years to develop a vaccine against prion disease. In his early efforts, he purified prion protein from bacteria and injected it into mice to try to get them to develop antibodies against the protein [Sigurdsson 2002]. Later he turned to developing Salmonella that produce prion protein, and injecting those bacteria directly into mice [Goni 2005, Goni 2008]. Most recently he has applied this approach to trying to prevent deer from being infected with chronic wasting disease [Goni 2015].

Q&A Panel 1

There were a number of questions about the risk of chronic wasting disease (CWD) infecting humans or spreading to other animals. Dr. Larry Schonberger replied that he and colleagues at the CDC are taking a variety of approaches, including cross-checking hunting license records with reports of CJD, to figure out whether there is any increased risk of prion disease among hunters who may eat venison. So far they haven’t seen any evidence of increased risk, but he noted that if the incubation period is several decades, as seen in some cases with kuru, then it would be hard to know for sure yet. Dr. Telling stated that there is no evidence yet that chronic wasting disease has infected bears or wolves or other animals that predate deer and elk. In response to a question about whether humans have exposed to CWD but have not developed disease due to natural immunity, Dr. Telling also added that there is some evidence that human prion protein is not very prone to change its shape in response to CWD prions, so while the immune system may not be involved per se, there is probably some level of intrinsic human resistance to CWD.

Jean-Philippe Deslys

Dr. Deslys received a grant from CJD Foundation to develop human “mini-brains” in a dish as a model for studying CJD and trying to develop therapeutics. He began by discussing the history of the technology that he is using. In 2006, it was discovered that cells from adults, such as skin cells, can be “reprogrammed” to a pseudo-embryonic state by turning on just four genes that are active during embryonic development [Takahashi & Yamanaka 2006]. This discovery proved incredibly influential and earned the 2012 Nobel Prize in Physiology or Medicine, because once the cells are reprogrammed to an embryonic or “induced pluripotent” state, then can then be reprogrammed again to turn into a variety of different cell types. Therefore, for instance, you can take a piece of a person’s skin and eventually turn it into brain tissue. This technique became even more useful in the past two years when researchers discovered a method for turning these reprogrammed brain cells into “cerebral organoids” or “mini-brains” [Lancaster 2013] so that they have some of the same 3-D structure as a real human brain, just on a much smaller scale.

Dr. Deslys has been creating human “mini-brains” in his lab and is working on infecting them with prions and showing that he can detect the prion infection. He has also created “mini-brains” made from skin from patients who have genetic mutations that cause GSS. His plan is to eventually use these “mini-brains” as a way to test potential therapeutic compounds in the lab, in the hopes of developing a drug for prion diseases.

Julie Moreno

Dr. Moreno received a CJD Foundation grant to study something called “cellular chaperones”. She began by talking about how prions can be studied in cultured cells in a dish in the lab. She is currently a postdoctoral associate in Glenn Telling’s lab, and a few years ago the Telling lab developed a series of cell lines that can be infected with different types of animal prions including chronic wasting disease [Bian 2010]. But like all cellular models of prion disease, the Telling lab’s cells have the property that it is fairly hard to get the cells infected with prions. Some cells are called “sensitive” (S) - they can be infected with prions - and others are “resistant” (R) and cannot be infected. She developed the hypothesis that differences in gene expression - which genes are turned on or off in the cells - determine which cells will be sensitive and which will be resistant. She therefore sequenced RNA from many sensitive and resistant cells in the lab, and quantified the different genes in the RNA to figure out which genes were turned on or off. She found hundreds of genes that were turned on at a higher level in the sensitive cells than the resistant cells and vice versa. But of course, because of natural variability between cells, some of these genes will just be coincidences - not all of them are actually important for determining which cells can be infected with prions.

Dr. Moreno said the most interesting result from her study of the RNA was that a gene called HSPB8 appeared to be more highly expressed - turned on at a higher level - in the cells that were “sensitive” and could be infected with prions. This gene is thought to be involved in a cellular machinery called the unfolded protein response. The unfolded protein response is supposed to be protective - it is activated when cells are filled with misfolded proteins and tries to keep things under control. But during Dr. Moreno’s PhD work in the Mallucci lab, she studied the unfolded protein response and found that it actually hurts more than it helps during prion disease, because it turns down the production of many important proteins while failing to halt prion protein production [Moreno 2012, Moreno 2013]. She said that HSPB8 also seems to become turned on in the brain in a mouse model of GSS.

She also has about 6 or 7 other candidate genes that she thinks may be involved in this machinery and seem to be important based on her analysis of the RNA. She is going to be investigating those in the future.

Christina Sigurdson

In prion disease, all neurons can become infected with prions, but some types of neurons are more likely to die than others, and different strains of prions or different genetic mutations are associated with more damage to different parts of the brain. A longstanding mystery is why some neurons are more vulnerable than others.

Dr. Sigurdson won a CJD Foundation research grant to study this question. She hypothesized that the answer might have to do with something called “heparan sulfate proteoglycans”. This term refers to large protein-sugar complexes that are found on the outside of cells, forming a sort of forest of sugar chains in the environment where the prion protein normally resides. Decades ago, it was found that these sugars can become part of the prion protein plaques in the brains of patients with CJD [Snow 1989], and Byron Caughey has found interesting results showing that synthetic sugar chains similar to these naturally occurring ones can affect the conversion of prion protein into its infectious form. Somewhat paradoxically, these synthetic chains can either make prions reproduce faster or more slowly, depending on whether the experiment is done in cells or with just purified protein [Caughey & Raymond 1993, Caughey 1994, Wong 2001]. One such synthetic sugar chain has even been used to treat prion disease in mice [Doh-Ura 2004].

The chemistry of these sugar chains - their length, shape, the number of sulfate groups, and so on - varies between different types of neurons. Dr. Sigurdson therefore hypothesized that this might be what controls which neurons are most prone to die due to prion infection.

Dr. Sigurdson has now confirmed Byron Caughey’s results showing that two types of synthetic sugar chains do indeed have the surprising property that they help cure prion infections in cells, but they actually increase prion formation in PMCA, which is an experimental procedure using sonic energy to amplify prions. Now, working with Dr. Qingzhong Kong at Case Western, she has obtained mice that are genetically engineered to have shorter sugar chains in the environment outside the cell, and she is testing whether this affects their susceptibility to prion disease or the properties of the prions produced by these mice.

Q&A Panel 2

In the Q&A there was much discussion about the different therapeutic strategies for CJD that the various research projects tie into. For instance, Dr. Deslys’s mini-brains could provide a way to screen chemical compounds, Dr. Moreno’s work touches on ways to target the neurotoxicity of prions, and Dr. Sigurdson’s work touches on the abilty of synthetic sugar chains to interfere with the ability of prions to multiply. The consensus was that it is worth pursuing a wide variety of different approaches in the hopes that one pays off, or that a combination therapy will prove more effective than a single approach.

Wenquan Zou

Dr. Zou has received multiple research grants from CJD Foundation over the years, most recently this year. He launched a project to collect skin samples from healthy, asymptomatic people who have genetic mutations that cause prion disease. As controls to compare those people to, he also collected skin samples from several people without genetic mutations, and people who were ill with sporadic CJD. From each skin sample he isolated a type of skin cell called fibroblasts. He has been growing those fibroblasts in his lab and using a variety of techniques to look for any differences between the people with and without mutations. For instance, he used fluorescent staining under a microscope to look for any differences in the mitochondria or the shape of the cells depending on whether they had a mutation. He also looked for any differences in the biochemical properties of the prion protein between the mutant and control cells. For instance, in the brains of patients with CJD or other prion diseases, you can find prion protein that is clumped together and will not dissolve in solution, even with detergent, and it is hard to break down with enzymes called proteases, which can normally digest any protein. He looked for whether the cells from people with mutations had similar biochemical properties. And he used RT-QuIC (a laboratory test introduced above, under Byron Caughey’s talk) to see whether the cells contained prion “seeds”. He presented preliminary results from all of these tests and expressed his hope that these techniques may one day offer a way to diagnose prion disease using skin samples. He is complementing his human studies with similar studies of the skin of prion-infected mice.

He has also reprogrammed the fibroblasts to become neurons, using techniques that were introduced earlier today by Jean-Philippe Deslys (above). In the neurons, he examined the loss of synapses, which is a process associated with neurodegeneration.

Emiliano Biasini

Dr. Biasini recently received his second CJD Foundation research grant. His first one was in 2011 and supported the beginning of the work that he is now continuing with his 2015 grant.

He opened with a slide on the thermodynamic journey of a penguin colony. He talked about how emperor penguins can be found as individuals in the Antarctic summer but the colder it gets, the more they aggregate together into large groups to shelter each other from the cold. He pointed out that prion protein has a similar journey. When a protein is first synthesized in the cell, it is just an unfolded chain of amino acids. Soon, it usually folds into a defined, healthy shape called the “native” state - the state in which the protein is usually found in our bodies. Sometimes it can partially unfold, or misfold, and from that point it can start to clump together with other copies of the prion protein, and eventually this can lead to large aggregates of prion protein, just like the huge mass of emperor penguins.

He raised the question of which stage in this process is easiest to target with a therapeutic. Some form of the misfolded and/or aggregated form of prion protein is infectious, and that is what causes CJD and other prion disease. But it has been very difficult to define exactly which misfolded form is responsible for the disease: we don’t know its exact shape, or how many copies of the prion protein it contains. That makes it difficult to develop a drug to stick to the misfolded form. Moreover, there have been some studies indicating that by the time neurons begin to die in prion disease, the infectious form of the protein is no longer multiplying [Sandberg 2014]. Dr. Biasini argued that the best way to fight prion diseases might be to reduce the amount of prion protein produced in the first place, but that this is hard to achieve. He has therefore focused his efforts on the “native” state of the protein. His goal is to discover a molecule that will stick to this form of the protein and will stabilize it, keeping it from unfolding or misfolding or sticking itself onto other copies of the prion protein.

Dr. Biasini next reviewed whether there are any already known molecules that are able to bind to the healthy prion protein and stabilize it. He used a technique called surface plasmon resonance (where you attach proteins to a slide and then test which molecules will stick to them) and another technique called equilibrium dialysis (where you let molecules flow back and forth through a membrane in water and see whether they all end up on the side where there is protein) to re-test all of the molecules that other researchers have previously claimed stick to the healthy prion protein. He found that almost all of the molecules that others had talked about in published papers didn’t actually bind to the prion protein after all. Only one molecule, called a “cyclic tetrapyrrole”, clearly did bind to prion protein [see also Nicoll 2010] but that molecule had poor pharmacokinetics (it was very unstable in the body), which meant that it couldn’t be developed as a drug.

He therefore set out to find new molecules that bind to prion protein, using an elaborate multi-step pipeline with different experiments at every step to test and re-test whether the molecules really bind, and to eliminate false positives. At the end of all this, he finally did find one new molecule that binds to prion protein. But unfortunately, this molecule was also pretty hard to develop as a drug - it was flushed out of the bloodstream too quickly, and it was not easy to chemically modify it to try to achieve better properties. He has continued his search and right now he has another new molecule that looks more promising than the previous candidates. He has confirmed that it binds to prion protein and that it slows down prion formation in cells, but he is going to do more chemistry to try to improve the molecule before he tries testing it in mice.

Q&A Panel 3

A couple of audience members asked why we can’t just delete the prion protein gene in people who have CJD. After all, we know that deleting the prion protein gene in mice cures prion infection, and people with CJD are on their deathbed anyway, so there shouldn’t be a major safety concern. Several people gave answers. Michael Geschwind explained that the bigger concern is feasibility, not safety — the deletion of the gene in mice was done through genetic engineering manipulations that are only possible to do in the lab before the mice are born, and we do not yet have the technology to delete the gene in living humans. Emiliano Biasini added that even if we did have a drug to do this, it is very difficult to get drugs into the brain. It requires a lot of chemistry efforts to deliver a drug to the brain, and he believes that his own efforts are still many years from resulting in any clinical trials. To specifically address the safety issue, Brian Appleby offered an analogy from Alzheimer disease. He explained that some of the antibodies developed to treat Alzheimer disease were tested first in patients with advanced disease, and were shown to be safe but didn’t clearly help the disease, so now they are being tested in asymptomatic people with muations, in the hope that earlier treatment will work better. So there is indeed historical precedent for testing a drug first in patients with very severe disease and later moving to asymptomatic patients.

One person asked whether GSK2606414 would eventually be tested in human clinical trials, and if so, whether it would be used in symptomatic patients or in asymptomatic patients who have genetic mutations. Michael Geschwind spoke up to point out that this experimental drug was incredibly toxic and actually killed the mice that were treated with it, casting doubt on whether it will ever reach clinical trials.

Jiri Safar

Dr. Safar delivered the annual update from the National Prion Disease Pathology Surveillance Center. He began with a review of the zoonotic potential of prions, meaning the threat of prions being transmitted from animals to humans. One of the Center’s major roles is to be on the lookout for BSE and variant CJD, but so far there has never been a case of vCJD acquired in the U.S. They also view chronic wasting disease as a major threat, but have not yet seen evidence for transmission to humans. Scrapie in sheep has been observed for hundreds of years with no evidence for transmission to humans, but there are atypical strains that are less well-studied, and they continue to surveill it.

He then discussed the new organizational structure of the NPDPSC. He described their recent success in implementing RT-QuIC as a diagnostic tool and stated that they are giving information back to clinicians based on RT-QuIC. He said they are continuing to work on enabling earlier diagnosis of prion disease.

Ryan Maddox

The CDC uses several approaches to surveill prion disease. They analyze death certificate data, but they acknowledge that this method will miss some cases because sometimes prion disease is not acknowledged on the death certificates, particularly if they did not undergo autopsy. They therefore also try to match death certificate data to referral data from the National Prion Disease Pathology Surveillance Center. Based on a combined analysis, they currently estimate an incidence of 1.5 cases per million population per year. This is slightly higher than in previous years, but some of this can be attributed to an aging population; age-adjusted incidence has been basically constant.

They also want to determine whether CJD is transmissible through blood transfusion. They examine this issue by looking at blood donation records of people who later die of CJD, and checking whether any recipients of their blood also developed CJD. So far, there is no evidence of transmission.

They are surveilling hunters, particularly in Colorado, Wyoming, and Wisconsin, to see whether there is any evidence for chronic wasting disease being transmitted to humans. They have 2.2 million hunting license records in Wyoming and 6.1 million licenses in Colorado, representing a total of 1.7 million unique hunters. A total of 15 hunters in this dataset have developed CJD, which is consistent with the overall prevalence of CJD and thus provides no evidence for transmission of CWD. In Wisconsin, they have a different mechanism, which is that whenever a deer tests positive for CWD, they ask the hunter whether they ate any of the deer, and if they say yes, then that hunter is monitored going forward. They currently have about 1,000 such hunters enrolled.

CDC is also making projections for future rates of CJD based on the aging populaton. They estimate that by 2030 there will be about 460 CJD deaths per year in the U.S.

They work with states to investigate particular cases of concern. For instance, they investigated an apparent cluster of CJD cases at a New Jersey racetrack, and determined there was no evidence for an acquired source of CJD. In many such instances, it turns out that not all of the reported cases are actually CJD, and some of the reported cases are genetic, and when accounting for the number of people potentially affected, the rate of CJD is consistent with expectation. They also monitor potential iatrogenic exposures, particularly after hospitals close, which makes it harder to track what happens afterwards. They investigated the one variant CJD case in the U.S. last year.

Finally, CDC also engages in outreach to the media and public to dispel misconceptions about CJD.

In the Q&A, someone asked how long the blood transfusion monitoring has been ongoing. Dr. Larry Schonberger said the program originated in 1995 when a particulary community was concerned about a man who developed CJD who had been a member of the “ten gallon club” for his prolific blood donatons.

Another question was whether CDC had done any twin studies on CJD. Dr. Maddox replied that they had not.

Kevin Keough

Dr. Keough gave an update on the activities of the Alberta Prion Research Institute. APRI was created in 2005 in response to the 2003 BSE crisis in Alberta. There have been additional BSE cases in Alberta since that time, but none have been linked to contaminated feed - they all appear to sporadic or genetic BSE, all in very old cattle, and the only reason that these cases are being noticed now is that they are looking harder for them, not that there didn’t used to be cases.

APRI has spent $50 million on research over the past 10 years. That round of funding expired in March 2015; Dr. Keough has just learned that APRI has been awarded $27.5 million for the next 5 years.

APRI’s largest project, costing $8 million so far, has been efforts to determine whether CWD is transmissible to humans.

Dr. Keough noted that there was one presentation at Prion2015 indicating that plants can take up prions from soil [Pritzkow 2015], but he urged that people take this result with caution, as researchers in Alberta have studied the issue and have not found that plants take up prions. He noted that different researchers use different methods, so different findings are not directly contradictory, but are a cause for taking results with a grain of salt. He also noted that dose is important: for prions to cause disease, they need to be present in sufficient quantities.

He also noted that they are particularly concerned about the risk of CWD for Alberta’s First Nation populations, and the possibility of spread of CWD northward into caribou herds.

Finally, he reviewed a few key recent findings from Alberta’s prion researchers. He touched on David Westaway and Jiri Safar’s findings that the brain produces less prion protein as prion infection continues, possibly representing some intrinsic protective mechanism [Mays 2014]. He discussed Valerie Sim’s findings that bile acids slow the formation of prions in cells in a dish, and slightly extend survival in male mice infected with prions [Cortez 2015]. Because bile acids are FDA-approved for an unrelated disease (a liver disease, primary biliary cirrhosis), Dr. Sim is now hoping to launch a clinical trial to see if these drugs can help CJD patients.

Amanda and Bradley Kalinsky

The pair introduced the process of in vitro fertilization with pre-implantation genetic diagnosis (IVF/PGD). This is a technology that has been use since 2001 for a variety of different genetic diseases [Verlinsky 2001], and allows a couple to create healthy embryos, genetically tested to not have the mutation, before implanting them. The process begins month or years before the couple has children, with genetic counseling and developing a custom genetic test for the embryos. When that is ready, the woman undergoes hormone treatments to produce eggs and have them extracted in the IVF clinic. The eggs are combined with sperm and the resulting zygotes are grown for 3-5 days at the IVF clinic before a few cells are taken and submitted for genetic testing. The process appears to be safe: there is no evidence for any increased rate of congenital abnormalities in IVF children. The genetic testing is about 99% accurate, so it’s not an absolute guarantee that your children will not have the mutation. The Kalinskys now have 3 healthy children with a 99% chance of not having the mutation. The whole procedure is fairly expensive and can cost about $35,000. How much of this you can get covered by insurance depends on what state you live in, which insurance company you have, and how much you advocate for yourself. People have gotten anywhere from 0% to 100% of the cost reimbursed by insurance.

These notes are not exhaustive; for more information, see some of the news about the Kalinskys, and this and this presentation, which are similar to the ones they presented today.

CJD International Support Alliance

Several family members told stories of their diagnostic odysseys and the clinical and interpersonal difficulties they had encountered with neurologists on the road to finding out that their loved one had CJD. Dr. Richard Knight gave a lecture about the underlying reasons for these sorts of difficulties being so common, ranging from the inherent difficulties of diagnosis — the same symptoms that are typical of CJD are also typical of many other diseases, some of which are more common and/or treatable — to interpersonal shortcomings on the part of some physicians. People also shared stories of loved ones being denied necessary surgery, or having difficulties scheduling funeral services, due to misconceptions about the risk of CJD transmission. CJD Foundation works to educate physicians and funeral home directors about these issues.

Suzanne Solvyns announced that CJDISA has unveiled its new website,

Advocacy training

CJD Foundation has issued two key requests for elected officials: continued funding for the National Prion Disease Pathology Surveillance Center at its current level, and increased oversight regarding the adequacy of USDA’s testing program for BSE. Dr. Jiri Safar spoke about the NPDPSC’s current activities and funding needs. Congress has given a $5.85 million annual appropriation to CDC for prion disease, about half of which goes to NPDPSC.

Nikki Hurt, a legislative aide on Capitol Hill, gave an advocacy training on how to talk to your elected representative about CJD. You’ll have about 30 minutes to meet with a congressional staffer focused on health policy. The most important thing to convey is your personal story, as this is what they’ll remember best later on. A typical elected representative will have about 3 staffers focused on health, and will accept all meeting requests from constituents, totaling about three meetings per day for each staffer. After you meet, include your talking points in a follow-up email so they have an electronic copy of it. It is recommended to take selfies in front of your senator or congressperson’s office door and share it on social media.

In the Q&A, Michael Geschwind asked how to handle the situation where your elected representative does not sit on any committee relevant to the issue at hand. Hurt responded that even if someone is not on a committee, they can still weigh in with relevant staff, or when the issue comes up for a vote. Geschwind also said that many staffers inquire as to what additional asks people have, above and beyond the official talking points, and suggested that it may be worth discussing the need for increased research funding. Hurt responded that additional points, such as research funding, can be raised in the follow-up email. One audience member asked why CDC keeps half of the funds appropriated for prion surveillance. Dr. Safar responded that Dr. Ryan Maddox (see above) has described the important surveillance activities that CDC carries out, which complement the efforts of the surveillance center in Cleveland. The two organizations have a close and productive working relationship and the 50/50 split of funds is mutually beneficial.