Hello everyone. My name is Márcia Waddington; I am a neurologist and the coordinator of the center for the study of paramyloidosis. This center has been operating at the Federal University of Rio de Janeiro for over 40 years, and more recently, it has also been active within the amyloidosis care program at the América Samaritano-Vitória hospital complex in Barra da Tijuca. I will explain how this center was established—first within the public system at a university in 1984, and later, as of 2024, within the private sector. I will begin my presentation now: the establishment of a center operating since 1984 at a public university hospital—specifically, that of the Federal University of Rio de Janeiro—and subsequently at a private clinic.

These are my conflicts of interest.

I will start with the university and the structuring of this multidisciplinary center specializing in amyloidosis at the Federal University of Rio de Janeiro. It was created in 1984—actually predating my own involvement, as I joined the hospital in 1988—but from the very beginning, Professor Marleide, who founded it, was committed to creating a multidisciplinary team.

Much later, I secured a dedicated space so that we could bring all the specialists and the entire team together in one location. However, this journey—which began when I took on the role in 1988—has been deeply tied to the researcher’s passion and interests; as you will see later, this can be both a strength and a weakness. For a long time, we have collaborated with the French center—specifically with Professor Violaine Planté and Professor Gérard Said—initially at a different hospital and later at Henri-Mondor. It is crucial that we participate in all clinical trials for treatments and disease-modifying drugs. We were able to do this thanks to how we structured the center, working with agents such as tafamidis, patisiran, inotersen, vutrisiran, and eplontersen.

In 2006, we launched our first study, Fx-005, the pivotal trial for tafamidis. The year 2013 marked a major milestone, as we organized the first and only international symposium on amyloidosis at the UFRJ. Known as ISFAP, it was the final event of its kind; following its conclusion, a European congress and a congress of the International Society were held.

We had some money left over, so—since the hospital provided the space—we were able to set up the area, cover renovation costs, and purchase materials, furniture, and even vital equipment. This included an echocardiography system capable of measuring atrial strain—which detects a very early-stage cardiac abnormality—as well as the Sudoscan (pictured right next to this text), a highly practical tool for examining small peripheral nerve fibers, which are the first to be affected by the disease. Our goal was to stay ahead of the curve and offer patients an early diagnosis. It is worth noting that this is the only Sudoscan in Rio de Janeiro’s public health network, and very few facilities have echocardiography machines capable of performing that specific type of advanced measurement.

So, the center grew, became financially independent, and began hiring staff from outside the institution. It wasn’t ideal, but it was what could be done, and the staff worked reduced hours. This is just to give you an idea of ​​everything we tried to accomplish in a single day—or as soon as possible—for the patient, especially for those traveling from afar. To give an example regarding neurological progression: we conduct clinical evaluations using various scales (such as NIS or PND) and perform nerve conduction studies. We use the Sudoscan (which I showed earlier) and quantitative sensory testing. We also look at neurofilaments—though the cost is literally very high, so we do this sparingly, mostly for academic purposes. We also attempt to obtain central nervous system imaging. When necessary, we perform biopsies—primarily of the salivary gland—and have recently incorporated ultrasound to try to detect early-stage neurogenic bladder, which is also an early marker of the disease. Cardiac function must be assessed as well, given the highly systemic nature of the disease. Examples include determining functional class and performing tests for orthostatic hypotension, tilt-table tests, ambulatory blood pressure monitoring (ABPM), ECG, Holter monitoring, and echocardiography with atrial strain analysis (as previously mentioned), as well as cardiac MRI and scintigraphy. The latter is quite challenging here in Latin America, as we have only one gamma camera available, and sometimes it is out of service. We also analyze cardiac function biomarkers and assess many other aspects of the patient’s functional status, such as gait testing and various quality-of-life questionnaires—including COMPASS, ODS, KPS, and nutritional status indices.

My point in sharing all this is simply to highlight the complexity and effort involved, as well as the importance of having a multidisciplinary team to evaluate these factors, optimize the patient’s quality of life, and gain insight into the disease’s onset, progression, and response to treatment.

All of this effort is futile if we fail to actually get the treatment to the patient. Consequently, a crucial milestone in our work at the university was a presentation made in collaboration with ABPAR—the Brazilian Association of Patients with Amyloidosis. You can see me there with Fábio at the Ministry of Health in Brasília; we worked side by side for years to ensure that CONITEC—the government agency responsible for evaluating the adoption of new technologies and medications—recognized the significance of amyloidosis, established treatment guidelines, and approved the inclusion of the drug tafamidis. It was the first medication to be adopted—and remains the only one to date—by our Unified Health System, allowing it to be dispensed free of charge to over a thousand patients across Brazil. This represents a major milestone, not only due to the drug’s inclusion but also because it led to the creation of what we call a PCDT—a clinical protocol and therapeutic guideline focused on diagnosis. This protocol establishes a standardized operational method across Brazil for diagnosing and treating amyloidosis and for dispensing tafamidis.

To give you an idea of ​​our patient profile: we have around 360 patients. We used to participate in the THAOS registry—an international database that closed in 2022—so we had to look for an alternative. At the time, our cohort consisted of 360 patients, the majority of whom had the early-onset V30M variant (meaning onset before age 50); a significant proportion—35%—also presented with cardiac involvement. It is, therefore, a disease with a mixed phenotype.

At the university, we treat only transthyretin amyloidosis, and patients are referred to our center through various channels: via patient associations—with whom we have collaborated for many years—or through internal hospital referrals and referrals from healthcare professionals outside the hospital. Crucially, we also receive referrals directly from families whom we support; furthermore, patients can find us via our website and schedule appointments themselves. We treat patients from across Latin America, not just Brazil; many patients from countries with limited resources—such as Bolivia—travel to São Paulo or Rio de Janeiro for treatment. In Brazil, we currently have three mutations classified as endemic. One is the V30M mutation—the most common worldwide—linked to our Portuguese ancestry; it predominates in the southeast and south of the country. Another is the V122 mutation (valine replaced by isoleucine at position 122), linked to our African ancestry; while it predominates in the northeast, it is found throughout Brazil. Finally, there is a third mutation—isoleucine at position 107—which is also endemic to the northeast. Given this wide variety of presentations, mutations, and ethnic or cultural origins, diagnosis for patients without a clear family history can take years—up to five—and errors are frequent. Misdiagnosis rates, for instance in my own series of cases, reached approximately 26.6%.

And what are the main advantages and achievements of this type of center? Being an academic center, it aims to consolidate everything—everything necessary—in one location. This is excellent because it allows us to promote multidisciplinary care as early as possible, especially for patients traveling from afar or those without access to private healthcare. It is worth noting that 90% of the Brazilian population relies on the SUS—our Unified Health System—because they lack private insurance coverage. Consequently, we are able to conduct clinical trials and provide access to medications that patients otherwise would never have obtained. We played a key role in working with the Ministry of Health to make tafamidis available to over 1,000 patients across Brazil—a number that has since grown significantly. We can achieve early diagnosis by acquiring more advanced, state-of-the-art equipment—equipment that is, shall we say, better suited for early detection. We monitor hundreds of patients using an on-site multidisciplinary team and conduct extensive medical training—including numerous mentoring sessions, presentations, and hosting visiting professionals who come to learn from us. Our scientific output has also been substantial, which has greatly benefited the medical school.

But there are challenges, aren’t there? There are challenges in everything, especially when operations are centralized; all responsibilities fall upon the principal investigator—or PI—which is to say, myself. Over time, burnout becomes inevitable.

So, the Principal Investigator (PI) has to handle the management of the medical team, clinical trials, finances, and coordinators, and must answer to regulatory bodies. We, for instance, underwent two FJEI inspections during the course of our clinical trials, and it is evident that operational capacity is constrained by the rising number of cases and carriers… There is increasing discussion about the condition, and more people want to undergo DNA testing; consequently, we have to provide follow-up care for them. The complexity of this follow-up is growing as new methods are introduced. New centers with a greater focus on the cardiac aspects of the disease have emerged in Brazil—an area that previously received little attention there, unlike in centers in the United States and Europe. They began operating differently, and we need to integrate our efforts because, ultimately, the patient is the same person. Furthermore, these new medications entail an increasing workload, making it progressively more difficult and complex to conduct successive clinical trials while continuing to monitor patients after the studies conclude. Now, I would like to share my experience in establishing a multidisciplinary amyloidosis center within the private healthcare network. I was invited by the Américas Network—part of the Américas-Samaritano-Vitória Hospital Complex in Barra da Tijuca, Rio de Janeiro—which is a major hospital complex and the second-largest private healthcare network in Brazil. I brought with me nearly 40 years of experience regarding center creation, the challenges faced, the mistakes I wanted to avoid repeating, and the practices I wished to implement. We founded the center in 2024, presenting a work plan to the administration and defining the scope of the services we intended to provide. So, this center treats not only transthyretin amyloidosis but also other forms—such as hereditary types and AL amyloidosis, which is a hematological disease. The scope is therefore much broader; consequently, you will see that—in addition to the neurologist—we have a cardiologist, a hematologist, a nephrologist, and staff specializing in nuclear medicine, echocardiography, and so on. We are also very pleased that, thanks to the support of the Américas Network, we now have a dedicated nurse navigator to assist us. You see, this gives me access to the necessary diagnostic methods and the specialized personnel to operate them. I no longer think about simply purchasing devices and housing them in a single location, as they would end up being underutilized. We operate differently; our approach is dynamic, as we have the right experts available to turn to.

The preparatory process involved immersing ourselves in the literature to identify the latest guidelines—which, incidentally, are set to change in 2026 but are currently up-to-date and will be revised as soon as new ones are published. We then developed flowcharts for diagnosis, treatment, and “red flags” or warning signs. This preparatory phase, which included the necessary negotiations, lasted nearly a year. We launched the outpatient clinic in April 2025; initially, we operated on a single-shift schedule, but we later expanded to see patients in both the morning and the afternoon. We were allocated a larger room. Here, you can see the nephrologist and the cardiologist working almost simultaneously. As you know, there is a crucial link between the heart and the kidneys. Cardiorenal injury is not uncommon, making this interaction vital. In the morning, I work alongside the neurologist—conducting genetic testing, providing genetic counseling, and addressing neurological issues—while the afternoon is dedicated to cardiology and nephrology. By the end of the day, we have a comprehensive view of the patient. We can discuss the best treatment options and assess whether the condition has progressed. Thanks to the presence of a nurse coordinator, we can also integrate ancillary tests; she communicates with the secretary for Dr. Alex Felix—who performs echocardiograms—to schedule the procedure and the patient’s next appointment, and, importantly, she enters all the data into our databases. Consequently, decisions can be made that very same day. We have access to genetic counseling and testing. Both the cardiologist and the nephrologist working with me use POCUS (Point-of-Care Ultrasound)—a portable ultrasound device—to perform a quick scan of the renal area, allowing us to make immediate decisions. Of course, a comprehensive echocardiogram assessing “atrial strain”—performed by a specialist—is absolutely indispensable; however, because the equipment is integrated, and thanks to an understanding of the disease and the use of the portable ultrasound device, many decisions and therapeutic adjustments can be made immediately. We have already had two patients who—albeit regrettably through legal action—secured high-cost medications, priced at around 750,000 reais per dose.

Ultimately, that is how we have tried to work. There is increasing reliance on this type of care.

We are also attempting to conduct clinical trials at the Américas Institute. We already have the innovative therapeutic option of using CRISPR/Cas, which requires a single dose. The only treatment available through the SUS (public health system) is tafamidis—20 mg for polyneuropathy and 61 mg for patients over 60. Consequently, there is a significant limitation for patients who do not respond to tafamidis or for whom other medications are indicated; this is why it is so important for us to continue offering clinical trials in the private sector alongside our university work. We make it a practice to monitor patients—tracking their treatment response or disease progression—every six months or once a year, depending on the case. And, as I mentioned earlier, we continue striving to implement the best treatment model and patient care process, which is quite a challenge.

One crucial thing I have always done—both at the university and in the private sector—is to enter absolutely everything we do into the database. I believe that is what truly distinguishes a research center from a standard laboratory. It takes time and reduces our clinical capacity, but I think it is… It isn’t mandatory—I don’t mean to imply it is required for everyone—but it is a decision I made. I believe it is something every research center should do, and it relies heavily on the dedication of the physicians and the availability of a dedicated nurse coordinator who can enter all that data—and do so in real-time, which is also important.

In a short time, we have achieved a great deal in terms of outreach.

Regarding 2025, I only have data here that pertains to me—data which, unfortunately, I was ultimately unable to share with my colleagues. However, that entire team you see there—the nephrologist, myself, the cardiologist, and the cardiac imaging specialist—also delivered many other presentations. We have conducted numerous presentations at both national and international levels. Crucially, we will be participating in the upcoming guidelines from the EAN (European Academy of Neurology), the PNS (Peripheral Nerve Society), and the ISA (International Symposium on Amyloidosis). We intend to publish our findings and present at all major national and international congresses; this reflects our commitment to knowledge dissemination and continuing medical education. Here is another example: a visit from Professor Perlini for a clinical session and a “mentorship exercise” conducted alongside Professor Maiolino, a hematologist. The point I want to make is that operating within a private network can present challenges—specifically, a lack of orientation toward an academic mission—but our desire to share knowledge, combined with the “Red Américas” network incorporating amyloidosis treatment as a value-added service, has made so much possible.

As I mentioned, we have the abstracts presented at major congresses—along with ongoing lectures—and, looking to the future, an increasing focus on marketing, something achievable only within a private network. Active case finding (especially for cardiac cases), continuing medical education, mentorship—these are our commitments. What lessons can be drawn from practice? What works, and what limits a referral center for amyloidosis, when I consider my two career paths side-by-side? In my opinion and experience, the systemic barriers to sustainable amyloidosis care stem, first and foremost, from the need for institutional support. It is of no use for someone to be passionate about their work—doing everything in their power to attract clinical trials, secure space and funding, purchase equipment, pay staff, coordinate teams, manage finances, and deal with regulatory bodies—if they eventually burn out because there is no institution backing them up. That institution must foster succession planning; it needs to encourage people to join, help out, and pass on knowledge, while also taking charge of coordination for the years ahead. I faced this challenge in the public sector and had to build the center within the private network to prevent it from happening again. And it is often not easy. It is difficult to mobilize providers, supervisors, and directors regarding this type of disease, simply because it is a rare condition, and these individuals are concerned with much more significant, high-priority issues within the hospital. There are other, more urgent matters, so I believe it is crucial that we try to make the most of our human capital and resources. So, at the university, we ended up shifting toward a rare disease care pathway—avoiding a scenario where the equipment I purchased, for instance, remained dedicated to just a single disease. Instead, we aim to operate dynamically within a private network, rather than constantly trying to buy this, that, and the other thing and housing it all in one location—which, for an administrator, would undoubtedly make no sense. I’ll conclude there and thank you all very much for your attention.