Why I Do What I Do: Spotlight on Laci Weatherford, Volunteer Walk Leader August 1, 2017 by Lauren Eva Laci Weatherford is now in her 7th year as a volunteer leader for the St. Louis NephCure Walk. Her incredible efforts have helped grow the walk to a massive event, with more than 100 people in attendance and raising around $15,000 each year! We spoke to her recently to learn about her journey with FSGS and how she manages such a successful fundraiser. NKI: How did you become involved with NephCure? How long have you been involved? Laci at the St. Louis Walk in 2012. Laci: I believe the first time I found NephCure was in 2009 when I was diagnosed with FSGS. I researched on the internet and found the NephCure website. I must have provided my information and said I would like to get involved, because in 2011 I received an email saying they were going to have a walk in St Louis. The email asked if I would like to be on the committee. I said yes. The day I was on my first planning committee call, I discovered I was the committee, the only volunteer for the event that was about a month away. So that year I learned the very basics of putting together a walk and have been working on improving and growing our annual event ever since. NKI: Why do you devote your time and energy to this cause? If you feel comfortable explaining, what’s your personal connection to kidney disease? Laci: After I was diagnosed in 2009, I began my personal journey with FSGS and learned firsthand the terrible side effects of the drugs available and the lack thereof. I learned how precious the little things were and struggled to just get by day-to-day, enjoy my 2 year old baby, and take care of myself. I began to read more on the internet about this disease: sometimes it would be good and encouraging, sometimes not. It quickly became too overwhelming to read the stories from parents who had children struggling with these drugs and side effects. It broke my heart, and I felt it was so unfair. I had lived a good life up until my diagnosis; I enjoyed my childhood, but they were being robbed of simple joys. I received a referral for a specialist in NY and became so encouraged by his accomplishments and his knowledge of the disease. I have tremendous hope and belief the cure and proper treatments are out there. We just need the right people to have the right tools to make it happen. It takes a lot of work to put all the proper channels in motion, and I’m so grateful NephCure is there doing the work to keep progress in motion. I want to do what I can to help fund this process. Laci and members of Team Brayden at the 2016 St. Louis Walk. NKI: What’s the hardest part about being a walk leader? Laci: The hardest part is getting the word to participants. Since this is a rare disease, not many people have ever heard of FSGS or NephCure. Unless you or a loved one is personally impacted, then you are probably not looking for another charitable event to go to. I’ve got to find a way to find the patients and their families. Doctors aren’t willing to help most of the time because of HIPAA policies and various other reasons. NKI: What’s the best part? Laci: There is so much that warms my heart about the event. The first is my family. They drive 3 hours just to be in St. Louis with me on this special day. They also coordinate 75% of the activities and volunteer in any area I need. If it wasn’t for them, I literally couldn’t do this. Second is seeing the other patients. To see them smile and enjoy a day dedicated to them encourages me to keep going. I also love to see the growth in the event, which is the proof we are getting the word out there. My first walk had about 20 people and we raised around $2,400. The walk is now averaging between 100-120 people each year and we raise on average $15,000. That is just amazing to me. NKI: What has surprised you the most throughout your years of leading this walk? Laci: I’m surprised by how generous and easy is it to get donations. Most of the time all you have to do is ask. There are so many business that will gladly give you a gift card, services, or products to help you raise funds. There is no secret to fundraising or formula for getting donations—all you have to do is ask! Mostly likely you are going to get a yes. Laci, center, with family and friends at the 2016 St. Louis Walk. Congratulations and a big thank you to Laci and her supportive team for their incredible efforts each year! With their help, we are one step closer to finding better treatments and a cure for FSGS and Nephrotic Syndrome. We couldn’t do it without them! Interested in volunteering at a walk or creating a walk team? Great! Just email us at events@nephcure.org to get started.
Summer Research Roundup July 21, 2017 by Kylie Karley Summer Research Roundup Summer is a great time to catch up on reading! If you’re sick of beach novels or historical biographies, consider catching up on science reading with our pick of recently published articles. We combed through the literature and found some interesting and relevant publications that may be relevant to Nephrotic Syndrome patients and families. The articles are listed in no particular order, and we do not endorse or prefer any of the research studies. Enjoy! A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease. Authors: Hayek SS, Koh KH, Grams ME, Wei C, Ko YA, Li J, Samelko B, Lee H, Dande RR, Lee HW, Hahm E, Peev V, Tracy M, Tardi NJ, Gupta V, Altintas MM, Garborcauskas G, Stojanovic N, Winkler CA, Lipkowitz MS, Tin A, Inker LA, Levey AS, Zeier M, Freedman BI, Kopp JB, Skorecki K, Coresh J, Quyyumi AA, Sever S, Reiser J. Dr. Reiser, a previous NKI grant recipient and Scientific Advisory Board Member, was a major contributor to this research Abstract: Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels. Mechanistically, surface plasmon resonance studies identified high-affinity interactions between suPAR, APOL1 and αvβ3 integrin, whereby APOL1 protein variants G1 and G2 exhibited higher affinity for suPAR-activated avb3 integrin than APOL1 G0. APOL1 G1 or G2 augments αvβ3 integrin activation and causes proteinuria in mice in a suPAR-dependent manner. The synergy of circulating factor suPAR and APOL1 G1 or G2 on αvβ3 integrin activation is a mechanism for CKD. Full article: Published in Nature Medicine and accessible here. Long-Term Outcomes in Children with Steroid-Resistant Nephrotic Syndrome Treated with Calcineurin Inhibitors Authors: Nathan T. Beins and Katherine M. Dell Abstract: Steroid-resistant nephrotic syndrome (SRNS) is an important cause of chronic kidney disease (CKD) in children that often progresses to end-stage renal disease (ESRD). Calcineurin inhibitors (CNIs) have been shown to be effective in inducing short-term remission in some patients with SRNS. However, there are little data examining their long-term impact on ESRD progression rates. We performed a retrospective chart review of all patients treated for SRNS with CNIs at our institution from 1995 to 2013. Data collected including demographics, initial response to medical therapy, number of relapses, progression to ESRD, and treatment complications. A total of 16 patients met inclusion criteria with a mean follow-up of 6.6 years (range 0.6–17.6 years). Histopathological diagnoses were focal segmental glomerulosclerosis (8), mesangial proliferative glomerulonephritis (4), IgM nephropathy (3), and minimal change disease (1). Three patients (18.8%) were unresponsive to CNIs while the remaining 13 (81.2%) achieved remission with CNI therapy. Six patients (37.5%) progressed to ESRD during the study period, three of whom did so after initially responding to CNI therapy. Renal survival rates were 87, 71, and 57% at 2, 5, and 10 years, respectively. Non-Caucasian ethnicity was associated with progression to ESRD. Finally, a higher number of acute kidney injury (AKI) episodes were associated with a lower final estimated glomerular filtration rate. Despite the majority of SRNS patients initially responding to CNI therapy, a significant percentage still progressed to ESRD despite achieving short-term remission. Recurrent episodes of AKI may be associated with progression of CKD in patients with SRNS. Full Article: Published in Frontiers in Pediatrics and available here Optimal management of primary focal segmental glomerulosclerosis in adults. Authors: Séverine Beaudreuil, Hans Kristian Lorenzo, Michele Elias, Erika Nnang Obada, Bernard Charpentier, and Antoine Durrbach Abstract: Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular kidney disease that is revealed by proteinuria or even nephrotic syndrome. A diagnosis can be established from a kidney biopsy that shows focal and segmental glomerulosclerosis. This histopathological lesion may be caused by a primary podocyte injury (idiopathic FSGS) but is also associated with other pathologies (secondary FSGS). The first-line treatment for idiopathic FSGS with nephrotic syndrome is a prolonged course of corticosteroids. However, steroid resistance or steroid dependence is frequent, and despite intensified immunosuppressive treatment, FSGS can lead to end-stage renal failure. In addition, in some cases, FSGS can recur on a graft after kidney transplantation: an unidentified circulating factor may be implicated. Understanding of its physiopathology is unclear, and it remains an important challenge for the scientific community to identify a specific diagnostic biomarker and to develop specific therapeutics. This study reviews the treatment of primary FSGS and the recurrence of FSGS after kidney transplantation in adults. Full Article: Published in International Journal of Nephrology and Renovascular Diseases and available here Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome Authors: Eva Königshausen and Lorenz Sellin Abstract: The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS)) since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs) in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications. Full Article: Published in BioMed Research International and available here Autoimmune Thyroiditis and Glomerulopathies Authors: Santoro D, Vadalà C, Siligato R, Buemi M, Benvenga S. Abstract: Autoimmune thyroiditis (AIT) is generally associated with hypothyroidism. It affects ~2% of the female population and 0.2% of the male population. The evidence of thyroid function- and thyroid autoantibody-unrelated microproteinuria in almost half of patients with AIT and sometimes heavy proteinuria as in the nephrotic syndrome point to a link of AIT with renal disease. The most common renal diseases observed in AIT are membranous nephropathy, membranoproliferative glomerulonephritis, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic autoantibody (ANCA) vasculitis, and amyloidosis. Different hypotheses have been put forward regarding the relationship between AIT and glomerulopathies, and several potential mechanisms for this association have been considered. Glomerular deposition of immunocomplexes of thyroglobulin and autoantibodies as well as the impaired immune tolerance for megalin (a thyrotropin-regulated glycoprotein expressed on thyroid cells) are the most probable mechanisms. Cross-reactivity between antigens in the setting of genetic predisposition has been considered as a potential mechanism that links the described association between ANCA vasculitis and AIT. Full Article: Published in Frontiers in Endocrinology and available here New insights into the pathogenesis of IgA nephropathy Authors: Yeo SC, Cheung CK, Barratt J Abstract: IgA nephropathy is the most common form of glomerulonephritis in many parts of the world and remains an important cause of end-stage renal disease. Current evidence suggests that IgA nephropathy is not due to a single pathogenic insult, but rather the result of multiple sequential pathogenic “hits”. An abnormally increased level of circulating poorly O-galactosylated IgA1 and the production of O-glycan-specific antibodies leads to the formation of IgA1-containing immune complexes, and their subsequent mesangial deposition results in inflammation and glomerular injury. While this general framework has formed the foundation of our current understanding of the pathogenesis of IgA nephropathy, much work is ongoing to try to precisely define the genetic, epigenetic, immunological, and molecular basis of IgA nephropathy. In particular, the precise origin of poorly O-galactosylated IgA1 and the inciting factors for the production of O-glycan-specific antibodies continue to be intensely evaluated. The mechanisms responsible for mesangial IgA1 deposition and subsequent renal injury also remain incompletely understood. In this review, we summarize the current understanding of the key steps involved in the pathogenesis of IgA nephropathy. It is hoped that further advances in our understanding of this common glomerulonephritis will lead to novel diagnostic and prognostic biomarkers, and targeted therapies to ameliorate disease progression. Full Article: Published in Pediatric Nephrology and available here.
Ask your Senators to vote NO on the revised Senate health reform bill July 17, 2017 by Kylie Karley ADVOCACY ALERT: ACTION REQUIRED Ask your Senators to vote NO on the revised Senate health reform bill The Senate recently released a revised version of its healthcare reform bill entitled The Better Care Reconciliation Act (BCRA). This bill, like the House version, proposes state waivers, continuous coverage penalties, and deep cuts to Medicaid that would harm patients with costly and chronic health conditions. David O. Barbe, M.D., President of the American Medical Association, stated that “the revised bill does not address the key concerns of physicians and patients regarding proposed Medicaid cuts and inadequate subsidies that will result in millions of Americans losing health insurance coverage.” This version of the BCRA adds an amendment from Senator Ted Cruz that would allow insurers to offer plans that do not meet Essential Health Benefits requirements, as long as these insurers offer at least one plan that does. Chris Hansen, President of the American Cancer Society Cancer Action Network, stated that the amendment and the bill as it stands would “leave patients and those with pre-existing conditions paying more for less coverage and would substantially erode the progress our nation has been trying to make in providing affordable, adequate, and meaningful coverage to all Americans.” This bill harms patients with chronic and complex illnesses in the following ways: Allows insurers to offer less comprehensive policies through a provision that allows states to waive the federal mandate on Essential Health Benefits Includes an amendment that would allow insurers to offer low quality health insurance benefits in place of comprehensive benefits under current law Allows states that seek and receive waivers to opt out of limits on patient out-of-pocket costs and annual/lifetime caps Contains a continuous coverage requirement, which would charge a penalty to individuals with a gap in their insurance coverage Ends Medicaid expansion, leaving millions of the most vulnerable individuals without critical care. The Congressional Budget Office (CBO) is anticipated to release its analysis of the bill by Monday, and a vote on the bill could take place anytime before the Congressional recess in August. Take Action: Secure the contact information for your Senators by visiting www.Senate.gov and using the “Find Your Senator” query tool in the upper right corner. Call the office and ask for the Health Legislative Assistant. You can either leave a voicemail or request their e-mail address and send them a message using the template below. Politely and occasionally follow up on your request. You should have an expectation that the office will respond to your specific concerns. If you would like to do more, you can request a brief meeting with the staff at your Senators’ local offices (the location office information is on their websites). Template For Emailing Your Senators Dear _______, My name is _________ and I am a constituent from _________. I am also an advocate for (your health condition). I write to urge you to vote NO on the Senate’s healthcare bill. The Senate healthcare bill would: Jeopardize patient access to quality, affordable & available coverage Cut-off health coverage for millions of Americans Bring back annual and lifetime caps on coverage Price people with pre-existing conditions out of the insurance market I write to urge you to maintain stability for chronic disease patients as you and your colleagues consider healthcare reform. It is my hope that you and your colleagues in the Senate will preserve key patient protections and respect the circumstances of those combatting chronic and costly illnesses. Specifically, please ensure any Senate proposal: maintains essential health benefits prohibits pre-existing condition discrimination prohibits lifetime and annual caps on benefits limits out-of-pocket costs for patients in a meaningful way allows young adults to stay on family coverage until they are 26 [Add a paragraph of brief information about your condition. Tell your story.] Patients need a transparent, bipartisan effort to stabilize the insurance market, bring down premiums, and retain the patient protections that are so critical to patients, consumers and their families. We urge the Senate to go back to the drawing board, and work together to find ways to protect patients with serious illness. Thank you for your time and your consideration of this letter. Please tell me how you have responded to my request. Sincerely, [Name] [Address]
Advocacy Alert: Action Required! June 30, 2017 by Kylie Karley Ask your Senators to Vote NO on the Senate Healthcare Repeal Bill Last week, the Senate released their version of health reform legislation entitled The Better Care Reconciliation Act (BCRA). The bill was slated for a vote this week but, after fierce opposition from the public health community, the vote has been postponed until after the July 4th recess. The bill is expected to undergo some changes in order to gain the support of Senators that have thus far withheld support of the measure. The bill, while seeking to reduce insurance premiums and provide coverage options to individuals with high healthcare costs, harms patients in the following ways: Limits care for people with pre-existing conditions by allowing insurers to offer less comprehensive policies through a provision that allows states to waive the federal mandate on essential health benefits. While insurers will still be required to cover individuals with pre-existing conditions, these individuals may not have all their treatments and services covered. Decreases insurance coverage by allowing states to seek and receive waivers to opt out of limits on patient out-of-pocket costs and annual/lifetime caps. Contains a continuous coverage requirement, which would charge a penalty to individuals with a gap in their insurance coverage. Increases costs for older Americans. Insurers would be allowed to charge older Americans five times more than younger Americans for the same coverage. Ends Medicaid expansion, leaving millions of the most vulnerable individuals without critical care. The Congressional Budget Office (CBO) has stated that the BCRA would cause: 15 million more people to be uninsured next year. In ten years, that number would grow to 22 million people uninsured. Patient out-of-pocket expenditures to rise dramatically, especially for people in states that opt for Essential Health Benefits waivers. The prohibitions on annual and lifetime benefit caps could be eliminated in states that opt for Essential Health Benefits waivers. Now is the time to weigh in with your Senators and make sure they oppose the BCRA as currently proposed and make sure they go back to the drawing board and work together to find ways to protect patients with chronic and costly medical conditions. Take Action: Secure the contact information for your Senators by visiting www.Senate.gov and using the “Find Your Senator” query tool in the upper right corner. Call the office and ask for the Health Legislative Assistant. You can either leave a voicemail or request their e-mail address and send them a message using the template found here. Politely and occasionally follow up on your request. You should have an expectation that the office will respond to your specific concerns. If you would like to do more, you can request a brief meeting with the staff at your Senators’ local offices (the location office information is on their websites).
Dr. Peter Mundel, Kidney Disease Researcher May 31, 2017 by Lauren Eva Why I Do What I Do: Spotlight on Dr. Peter Mundel, Kidney Disease Researcher Dr. Peter Mundel is a physician-scientist who has spent the past 30 years studying kidney cells called podocytes, which are specialized cells with a central role in glomerular diseases like FSGS. Dr. Mundel has been an esteemed member of NephCure’s Scientific Advisory Board since 2007, and in 2011, NephCure helped fund his work by providing him with a bridge grant. A major focus of his work has been the development of new, targeted treatments for patients with FSGS and other glomerular diseases. Last year, he left his professorship at Harvard Medical School/Massachusetts General Hospital to lead the research of a new start-up company called Goldfinch Bio, a biotechnology company that is singularly focused on discovering and developing precision therapies for kidney disease. We spoke with Dr. Mundel about his work and what inspired him to leave academia to create new treatments for people living with FSGS and Nephrotic Syndrome. NKI: How did you first become interested in studying the kidney? What is it about glomerular diseases specifically that interests you? Dr. Peter Mundel Dr. Mundel: I first became interested in studying the kidney when I was in medical school, back in Germany in the late ‘80’s. I had joined the laboratory of Dr. Wilhelm Kriz, who was one of the leading investigators in the field. At that time, there was nothing known about podocytes. They were considered passive bystanders. Everybody was thinking about mesangial cells and their role in the pathogenesis of kidney disease. So, I saw an opportunity and I entered the field and started to work on podocytes, and that’s what I focused on for 30 years since then: I got into the biology of these cells, learned about their function in health and disease, and then later of course I was trying to find podocyte-targeted therapies. But it all started 30 years ago in medical school in Germany. I still remember how I would sit with Professor Kriz in his office and we would say “one day we should develop podocyte protective medicines.” That’s what we said, and 30 years later, we’re doing it! NKI: Could you tell us about your discovery process of deciding to study a new drug? I am thinking specifically of abatacept because many people in our community are familiar with it, and I know you were instrumental in discovering its use in treating Nephrotic Syndrome. Dr. Mundel: We can definitely talk about the abatacept story, because it has good parallels, and it also helps explain what brought me to Goldfinch Bio. We identified B7-1/CD80 in podocytes, way back at my lab in Heidelberg, using differential Display PCR, a technique that allows you to monitor changes in gene expression between normal and diseased cells. We had our first paper on B7-1 in 2004 in The Journal of Clinical Investigation, where we showed that B7-1/CD80 has a role in podocytes in proteinuria, in addition to its role in the immune system. We studied the role of B7-1/CD80 in podocytes for another for 10 years, and then we began studying the use of abatacept [which targets CD80/B-71] in patients. What’s interesting with abatacept is that we now know that there is a subgroup of patients that respond well to this drug. Going forward, the challenge will be in identifying with precision who are these patients for whom it will work. There is no silver bullet: not every patient with Nephrotic Syndrome and FSGS will respond to the same drug. Some people will respond to abatacept and some people will respond to some as-yet-unidentified new drug. We will need to take a precision medicine approach. Knowing this, we will now need to define patients molecularly—not by saying they have FSGS or proteinuria, but by saying they have proteinuria driven by CD80/B7-1, or by protein ‘X’ or protein ‘Y’. That is exactly what our colleagues in oncology do: when you have a mutation in BRAF [which causes, for example, skin cancer or melanoma], you get a BRAF blocker for your melanoma. At Goldfinch, we are basically bringing the oncology playbook to the kidney space. We need to figure out who will respond to which drug, and we will need to use people’s genetics to identify targets for new, specific drugs. I think abatacept was the first stop at personalized medicine. When our paper [on abatacept] came out, there was an accompanying editorial by Börje Harraldsson that said exactly that—“A New Era of Podocyte-Targeted Therapy.” There is a trial going on with abatacept right now. I’m very pleased about that, because if you see in our original New England Journal of Medicine (NEJM) paper, patient number 5, this woman was on and off all kinds of drugs. But abatacept works so well for her that she is now in complete remission. And now, in her late 20’s, for the first time she has a good life; she enjoys her life. She doesn’t go from medicines with side effects to being hospitalized as she used to. I think this is a great success, because this is an idea that started in my lab almost 20 years ago. Because of this work, there is someone who really feels good and has a good life. And so as I said, the challenge now is to find all those patients who will respond to each of our precision treatments. NKI: Wow. That must make you feel incredible to know that years and years of your research led to this woman finally feeling like she could have a good life. Dr. Mundel: It’s a humbling experience. It’s very humbling that I had the privilege to have an impact on someone’s life. Because you see, I’m an MD by training, but after medical school I have only done research. But indirectly I act like a physician—I don’t treat her myself, but because of my work, she now has a better life, and I’m very happy for her. For all of our patients at NephCure that we care about with FSGS and Nephrotic Syndrome, I think this is a beacon of hope. For some of them [abatacept] will work too, and for others we will now find new drugs. But it clearly shows that the overall idea of finding podocyte protective drugs is a good idea, and it can work. NKI: So in the future, how would what you’re describing work? Would patients come in to their clinician and have gene mapping done, and when the results come in, their clinician would know exactly how to treat them? Dr. Mundel: That is basically the end goal. At Goldfinch, we are building a patient registry where we will sequence thousands of patients with FSGS. This will allow us to stratify patients, so when we have a drug that we know will work for a certain pathway or mutation, we will be able to select patients who can benefit from this drug. We will be able to say, “You have a mutation in protein ‘X’, so we are giving you a drug correcting the effects of protein ‘X’ mutation.” That’s the targeted approach that we’re talking about when we refer to precision medicine. At the same time, we need to identify more causes of FSGS. The work done by Dr. Martin Pollak and Dr. Friedhelm Hildebrandt has identified a lot of these genes, and there are even more to be found. What their work shows is that there is a genetic underpinning of FSGS. At Goldfinch, we will continue that work and work closely with many academic collaborators. So to answer your question more directly, down the road what you described is exactly what we are going to bring to patients with kidney diseases. At some point, the patient comes in and they have proteinuria, and their doctor will do a genetic test. Right now, we can do it for about 70 or 80 genes [that are associated with FSGS and Nephrotic Syndrome], somewhere in that ballpark. Down the road, there may be hundreds, and patients will be tested for them. And we will have different medicines, so based on the patient’s mutation, we will be able to give them a specific treatment. We will no longer give patients nonspecific steroids or cyclosporine, but instead give them a targeted medicine because we will understand exactly what’s causing the disease. That’s what we want to do at Goldfinch—bring this personalized medicine to patients with FSGS. NKI: Right, and that way they’re not wasting time cycling through drugs that aren’t working, and in the meantime, not just not having a very great life, but also heading towards end stage kidney disease. That will save a lot of time. Dr. Mundel: Exactly. That’s the other goal—we want to prevent patients with FSGS to progress to end stage kidney disease and from going on to dialysis. At Goldfinch, our goal is to prevent people from going on to dialysis or needing a transplant—to stop the disease in a specific way by addressing the root cause. NKI: This is fascinating. And before you mentioned Dr. Pollak and Dr. Hildebrandt’s work, which has been funded in part by NephCure, I was going to refer to it and say, it’s really interesting from an outsider’s view how all this research is culminating: the genetic research, and drug discovery research, and podocyte research. It seems like it’s finally all coming together. Dr. Mundel: Oh, absolutely. Let me give you a prime example. My own work has been focused on the podocyte actin cytoskeleton. Independently, over the last five or six years, geneticists identified several FSGS causing mutations affecting the podocyte cytoskeleton. We now understand the genetics of the podocyte cytoskeleton, and this dovetails with what we understand about the biology. We are living in a time when genetics and biology are coming together. When you have both, then you can have the precision and the tools to make a targeted therapy. NKI: Wow, what an exciting time to be a glomerular disease researcher. That excitement and that feeling of being just around the corner, that must have been part of what led you to leave academia. You had a very distinguished position at Harvard, and you left it to join Goldfinch Bio. That speaks volumes of your confidence in it. Dr. Mundel: It does, and I believe that what we’re doing is the right thing. I’ll tell you, when I first came to Harvard in 2010, I thought I would continue doing academic research until I die in my office. And then this amazing opportunity came. As we discussed, it’s the dovetailing of the biology and the genetics, but also the work done by Dr. Melissa Little and by Dr. Joseph Bonventre, who’s one of our founders. They showed that it is possible to make kidney organoids, which are “kidneys in a dish”. So now we have the ability to study human kidney disease, if you will, in a dish. There’s also been an explosion of technical data, where analyzing the genetic data is becoming cheaper and cheaper. And cloud computing has arrived, which we didn’t have five years ago. Now we have all the computational tools, the biological tools, the genetic tools to bring such a push to this field. It’s absolutely exciting. In 2008 we had a manuscript where we showed how cyclosporine, which is clinically used to treat NS, works on podocytes. Then we had the NEJM paper where we repurposed the drug abatacept from Rheumatoid Arthritis to patients with FSGS. Joining Goldfinch was the next logical step. I want to make new drugs targeting the causes of the diseases, and I think Goldfinch is the perfect place to do it. And as you said my confidence is reflected in the fact that I have left Harvard. I’m not on a leave of absence, I have not kept my professorship; I have shut down my laboratory and returned all my grants and funding. I want to focus on Goldfinch now, because by focusing on it we can do our best. I wholeheartedly believe in what we are doing here, and I wholeheartedly believe that we will be successful in helping our patients. They really need new treatments. There are no drugs approved in the US to treat FSGS, and the last approved therapy to treat proteinuric kidney disease occurred over 20 years ago. It is pretty much the same since I graduated from medical school in 1991 . It’s time to bring a renaissance and provide new therapies for our patients. For me there is no better mission than doing that. The goldfinch was a prominent symbol during the Renaissance, and signified hope and a new beginning. We chose to name our company Goldfinch Bio because we feel that the vision of our company is to lead a renaissance in developing new therapies for patients with kidney disease. I think it’s a sign of hope and optimism that there’s a new chapter, a new age that we are ushering in and that we want to lead. Because the patients deserve that we find good therapies for them. I’m proud to be part of the team here at Goldfinch that will do exactly that: find new therapies for patients with kidney disease. For me there’s nothing better that I can think of doing with my time. We were thrilled to speak with Dr. Mundel and learn more about his latest venture. Researchers like Dr. Mundel and many others provide us with real hope and conviction that we will one day find a cure for the diseases that cause FSGS and Nephrotic Syndrome. Since 1999, NephCure has helped provide funding for more than 50 research projects to learn more about causes and potential cures for the diseases that cause Nephrotic Syndrome. Today, these researchers are closer than ever to moving new treatments from the laboratory to the pharmacy shelf. Thank you for your commitment to this work, Dr. Mundel, and all who have dedicated their lives to eliminating these rare and chronic diseases! Dr. Peter Mundel is a past awardee of the esteemed American Society of Nephrology Young Investigator Award and a distinguished investigator who lead the Mundel Laboratory at Massachusetts General Hospital and Harvard Medical School from 2010 to 2016. In April 2014, Dr. Mundel received, jointly with Dr. Anna Greka, Renal Division, Brigham and Women’s Hospital, a 2014 Top 10 Clinical Research Outstanding Achievement Award from the Clinical Research Forum. In 2013, he and distinguished colleagues published the first targeted treatment for proteinuric kidney disease in the New England Journal of Medicine. (Abatacept in B-71; N Engl J Med 2013; 369:2416-2423). The associated editorial in the NEJM describes their discovery as a “New Era of Podocyte-Targeted Therapy for Proteinuric Kidney Disease.” Dr. Mundel attended medical school at the University of Heidelberg, Germany. He completed a Postdoctoral Research Fellowship in the program “Experimental Kidney and Circulation Research” at the University of Heidelberg, which was funded by the German Research Foundation. He is also the author or co-author of over 86 original research articles. Dr. Mundel’s research focus has been on the makeup and function of podocytes, key cells found in each of the one million separate filtration units packed into a single human kidney.
NephCure Funded Research: Dr. Alessia Fornoni May 27, 2017 by Lauren Eva NephCure Funded Research: Dr. Alessia Fornoni Dr. Alessia Fornoni is a physician scientist focused on better treating and one day, curing individuals with FSGS and other diseases that cause Nephrotic Syndrome. Early in her research career, she received a grant from NephCure, which enabled her to identify a new gene that plays a role in Nephrotic Syndrome. Her breakthroughs in research today could lead directly to a cure for FSGS. Recently, she shared with us her recollections of that experience and what receiving that grant meant for her work. -NKI I grew up on a goat farm in Italy. When I was 8, a local physician buying cheese at our farm encouraged my parents to send me to school in a nearby city. It was there that I first set my sights on becoming a doctor. Medical school brought me to the United States where, after several years in research, I became a nephrologist. Early in my nephrology training, I was fortunate to receive funding from NephCure. The grant I received from NephCure truly catapulted my career and solidified my interest in glomerular diseases like FSGS. In 2008, as a young investigator at the University of Miami, my NIH-funded research was focused on diabetic kidney disease. One day, I was approached by the Chief of Kidney and Pancreas transplantation, Dr. George W. Burke, who shared with me interesting results he gathered when utilizing rituximab in patients with post-transplant proteinuria. His findings sparked my interest—Why did a drug that was used primarily to treat cancer by depleting immune cells also seem to improve these patients’ kidney disease? I decided to investigate this phenomenon further. Dr. Alessia Fornoni With my team, I studied 27 individuals with primary FSGS who received kidney transplants. We were able to prove that preventive treatment with rituximab can reduce the chance of recurrence of proteinuria in patients with FSGS after their kidney transplant. This was groundbreaking. We hoped that our data could help patients with kidney failure due to FSGS, who are tragically at a 30-80% risk of redeveloping the disease after a kidney transplant. At this point, I knew that a new study was needed to confirm my findings and to demonstrate the direct mechanisms by which rituximab may protect the kidney. I had more questions and knew that there was more to learn. But without additional funding, I would not have been able to continue. I turned to NephCure Kidney International. Supporters like you have helped NKI create a research award program, open exclusively to glomerular disease researchers who have a focus on finding a cure for affected families and patients. Through this program, I applied for and received a Bridge Grant that allowed me to continue my work on rituximab. Because of this funding from NephCure, we made significant advancements in the field.We created a screening that enabled us to predict which patients would develop recurrent FSGS after their transplant. We also identified a new gene (SMPDL3b) that plays a role in Nephrotic Syndrome. This gene can now be targeted and used to help create new drug treatments. These discoveries give other researchers in this field building blocks to learn more about FSGS, potentially leading to additional breakthroughs. Before our discoveries with rituximab, I was primarily focused on diabetic kidney disease. Today, due in part to funding from NephCure which advanced my work, I have developed a strong interest in studying rare glomerular diseases, like FSGS. And like me, when you look at a list of the top glomerular disease researchers in this field, many of them received funding or other support from NephCure at some point in their career. Your donation to NephCure makes a difference. For me personally, you have allowed me to reach breakthroughs in my work on FSGS and other glomerular diseases. Can you make a donation today to ensure that research into Nephrotic Syndrome and FSGS can continue? Your gift can help support scientists early in their career, as I once was, who need additional support to study these rare kidney diseases. My battle to find a cure for patients with glomerular disease continues today. Recently, I discovered that a compound called hydroxypropyl beta cyclodextrin (HPβCD) may have benefits in the treatment of certain types of kidney disease. HPβCD has already shown promising pre-clinical results and is now being developed by Variant Pharmaceuticals to treat FSGS. I am hopeful about its potential to delay the progression of this chronic and often times debilitating disease. Thank you for your support thus far in our journey, and thank you for working alongside me in our joint effort to eliminate FSGS and other diseases that cause Nephrotic Syndrome. Together, I know that one day soon, we will find a way to eliminate the suffering caused by this condition. With gratitude, and with the commitment to work with you in finding a cure and training the next generation of physician scientists, Alessia Fornoni, MD, PhD Alessia Fornoni, MD, PhD, is a professor of medicine at the University of Miami Miller School of Medicine, the Peggy and Harold Katz Family Chair, the Director of the Peggy and Harold Katz Family Drug Discovery Center, and the newly named chief of The Katz Family Division of Nephrology and Hypertension. Dr. Fornoni’s research, which has been NIH-funded for the past 10 years, focuses on podocytes and mechanisms of proteinuria, lipid biology, insulin signaling, drug development, and target identification. Her clinical interests are in the area of diabetic kidney disease and of rare glomerular disorders, such as focal and segmental glomerulosclerosis, and Alport syndrome. As a mentor, Dr. Fornoni has trained more than 20 pre- and postdoctoral research fellows, several of whom have gone on to faculty or academic/research positions. She has published more than 90 original articles and is an internationally known lecturer.
Advocacy Alert! Ask Your Senator to Support FSGS Research Funding May 12, 2017 by Kylie Karley Advocacy Alert! Ask Your Senator to Support FSGS Research Funding Ask your Senator to to sign on to Senator Stabenow’s letter requesting that FSGS be eligible for research funding under the Department of Defense’s Peer Reviewed Medical Research Program for fiscal year 2018 Background Each year, the United States Senate crafts an annual Department of Defense (DoD) appropriations bill, which includes a list of conditions that are deemed “eligible for study” through the Peer-Reviewed Medical Research Program (PRMRP). In order for a condition to be included, Senators need to support the condition and officially ask for its inclusion. Senators have many competing appropriations priorities and in order for them to support a condition-specific request, they need to be educated and asked to do so by their constituents. (You) As a result of grassroots outreach, the Senate has recognized FSGS as a condition eligible for study annually for a number of years. This support allows FSGS researchers to compete for nearly $278 million in federal research funding each year. You can read about FSGS researchers that received funding for projects through this program here. Take Action Secure the contact information for your Senator by visiting www.Senate.gov and using the “Find Your Senator” query tool in the upper left corner of the page. Call the office and ask for the Health Legislative Assistant. You can either leave a voicemail or request their e-mail address and send them a message using the template below. If you call, you can use the template as a guide in your conversation. Politely and occasionally follow up on the request. You should have an expectation that the office will respond to your specific concerns. Email Template Dear _______, My name is _________ and I am a constituent from _________. I am also an advocate for the Focal Segmental Glomerulosclerosis (FSGS) community. FSGS is a rare and devastating disease that attacks the kidney’s filtering units (glomeruli), causing serious scarring, which often leads to permanent kidney damage and even failure. FSGS is a leading cause of end-stage renal disease (ESRD), kidney dialysis, and transplantation. FSGS is disabling, potentially fatal, and treatment options remain limited for affected individuals. Please join Senator Debbie Stabenow in requesting that Focal Segmental Glomerulosclerosis (FSGS) be listed as a condition eligible for study through the Department of Defense’s Peer- Reviewed Medical Research Program, and encouraging continued research at the National Institutes of Health (NIH) during consideration of fiscal year (FY) 2018 appropriations through important report language. FSGS is also a leading cause of end-stage renal disease (ESRD), which nearly 30,000 veterans suffer from nationwide. An additional 3,000 veterans are expected to reach ESRD each year with significant disparities among African Americans. In addition, researchers suggest that environmental exposures have yielded new opportunities for investigating FSGS in the military population. More needs to be done to improve our understanding of the impact of FSGS among our military personnel and veterans. Please consider adding your name to the letter by contacting Lorenzo Rubalcava in Senator Debbie Stabenow’s office at Lorenzo_Rubalcava@stabenow.senate.gov or 4-4822. This letter will close on May 18th, 2017. Thank you for your time and your consideration of this letter. Sincerely, [Name] [Address]
Why I Do What I Do: Spotlight On Susan Madigan, CureMaker April 3, 2017 by Lauren Eva We were thrilled to chat recently with Susan Madigan, a longtime supporter of NephCure and grandmother to a young granddaughter who has Minimal Change Disease. Susan has been involved with NephCure in many ways over the years, and we talked with her about the different events and programs she’s contributed to. One of the programs that Susan has been a member of is the CureMakers recurring monthly giving program—meaning she has signed on to contribute to NephCure on a regular monthly basis! Her support has truly made a difference in our work, and we’re pleased and delighted to have her as a member of our community and to share her story with you today. NKI: How long have you been involved with NephCure, and how did you first become involved? Susan and her granddaughter. Susan: My involvement with NephCure revolves around my concern for my granddaughter. She was diagnosed with Nephrotic Syndrome when she was four, and she’s now almost ten. I didn’t get involved right away in the beginning, not knowing much about it. And then I did, in 2012 I became more involved, and then I think I became a CureMaker. I’ve been coming to your Countdown to a Cure gala in New York and supporting my daughter’s walks in Los Angeles for a few years. And I’ve been to a couple of other things here in New York. I’ve been to the Countdown to a Cure gala two or three times now. One time I had a conflict, but from then on I’ve always blocked that whole period off. I know it’s in November, so I make sure I’ll be around for it. When my granddaughter was first diagnosed, she was swollen, and my daughter and son-in-law thought she had a bee bite or something. They hadn’t a clue what it was all about; no one did. She woke up swollen and they took her to the pediatrician who said “No, it’s not a bite.” They were able to figure out her diagnosis right away. She now has a wonderful nephrology support team in LA, including her long-time nephrologist, Dr. Elaine Kamil [who serves on the NKI board] as well as Dr. Dechu Puliyanda, her current day-to-day nephrologist. I don’t talk to my granddaughter much about it; we don’t hide it, but it’s not a constant topic of our conversation. At this point, she’s doing alright. Certain things could still be in the future for her that obviously, we can’t know, or that she can’t comprehend yet. We’re all very committed and we all try to stay on top of it, but some of it is still a big mystery in my life. But if there’s anything I can do to help, I’m thrilled to do so. NKI: You’ve been involved with so many activities with NephCure—what’s been your favorite thing so far? Susan: I love the walks—my daughter’s walk involves a lot of children. Her support group is full of children, and she has t-shirts made for everybody, so we all wear the same shirt. The kids have a banner that they carry. And I like that, because I think it involves the patient—the child—as well as his or her friends, so that they’re aware that something is happening there. I like that a lot. Susan’s granddaughter’s walk team at this year’s walk in LA. To me, the gala is also very special, because it gets everybody there and involved. You get all these great people there, and it’s pretty and a lot of fun. I think the auction is great because it raises money for NephCure. The last time I went, I didn’t realize my paddle was in my hand and I kept raising it, (laughs) and finally I thought, after the third time, you’ve got to put this on your lap! NKI: I know that you and your granddaughter live on opposite coasts. Does donating monthly to NephCure as a CureMaker help you feel connected to her? Susan and her granddaughter earlier in her journey with kidney disease. Susan: I think to contribute to an organization on a sustaining level is A. easier for the person who donates, and B. you always feel connected, not just at the end of the year, if you choose to donate then. I think it offers security for the organization to know that you have “X” number of people who will be contributing on a monthly basis. And for the people who donate, it’s a very convenient, painless way of doing it! It’s an easy way to contribute for people who want to give, but who may sometimes forget at the end of the year. I love it, I think it’s just wonderful. I also tell my granddaughter about it so that she knows I’m supporting her on a monthly basis. I really think NephCure is doing an incredible job—as someone said, it’s a disease without a cure, which is rather a disheartening way to put it, but certainly at this point there’s no cure for it. And anything I can to do help, I’d be thrilled to. NephCure would like to thank Susan for her unwavering and touching support in honor of her granddaughter. Without dedicated people like Susan, the work that we do at NephCure to provide support and education for people living with Nephrotic Syndrome and fund research to find better treatments and a cure would not be possible. Thank you, Susan! To learn more about the CureMakers monthly giving program, visit our donation page here or give us a call at 610-540-0186 x10. To hear more about a local walk in your area or our Countdown to a Cure gala in NYC, send us an email at events@nephcure.org to get connected with your regional manager.
NephCure Funded Research: Dr. Evren Azeloglu April 3, 2017 by Lauren Eva NephCure Funded Research: Dr. Evren Azeloglu Dr. Evren U. Azeloglu In 2015, Dr. Evren Azeloglu, a biomedical engineer and an Assistant Professor at the Icahn School of Medicine at Mount Sinai, was awarded the NephCure Kidney International-ASN Foundation for Kidney Research Grant. He planned to use this grant to explore how kidney cells retain their structural integrity against mechanical injury. Much of the work done in Dr. Azeloglu’s lab involves the podocyte, the specialized kidney cell that is affected by glomerular diseases like FSGS. Podocytes play an important role in glomerular function. Together with other cells, they help form a filtration barrier in the kidney, and they cooperate with other cells to support the structure and function of the glomerulus. Below, we discuss Dr. Azeloglu’s latest research and what it means for people living with glomerular kidney diseases in our search for better treatments and a cure. NKI: You’ve recently released two articles (here and here), both from research funded in part by NephCure. Can you tell us about your latest research? Dr. Azeloglu: Well, podocytes have a very beautiful structure, and we used cutting-edge imaging technology to capture the three-dimensional geometry of these cells. This paper is essentially about how the podocyte shape is not just pretty and sophisticated, but also very necessary for their function. And their shape has certain consequences for disease: some of the glomerular diseases may be directly borne out of the fact that these cells are shaped this way. If you look at the below gif, you will see how these cells look in the body. This is the first time anyone has ever visualized them with this kind of precision. NKI: Can you elaborate on what you mean when you say that their form suits the function? Dr. Azeloglu: Well let’s say that you want to build a drawbridge, and you want to be able to have tall ships travel below or through it. So you can either spend a lot of money and build a very tall bridge that is stationary, or you can build one that opens and closes. Basically, you are proposing a “functional upgrade” to a regular bridge. Unfortunately, that comes at a cost. The bridge needs to be able to separate in the middle. Following that analogy, podocytes have this special shape that allows them to do something that no other cell can do. What we are showing in our paper is that this special shape also comes with a price: incredible fragility. This works in the same way that a drawbridge has less stability than a regular arched bridge and would not be able to sustain the same level of, for example, an earthquake. You sacrifice that stability because you want to be able to open it up. In the same way, podocytes have incredible surface area; they have this amazing structure that allows them to filter blood plasma into urine, but what we’re showing is that only at this shape, the cells start showing this incredibly fragile behavior, and even a little change of their chemistry leads to disease. This ties in very well with the current knowledge that the podocytes are sort of the first guys to fail, if you will. This is one of the reasons why, for example, diabetic patients, whose cells are under constant stress because of insulin spikes, high levels of glucose, and all sorts of other oxidizing agents, are much more likely to develop nephropathy. So, what we are trying to show here is that these cells are incredibly fragile compared to most other cells in our body. NKI: What does it mean to be a biomedical engineer studying podocytes, and from a larger perspective, kidney disease? Dr. Azeloglu: I approach kidney research from an engineer’s perspective: the same way we study machines, buildings, and structures that have to withstand physical stress, which is exactly what podocytes have to do day in and day out. What we’re looking for, and what most of the projects in my lab focus around is: can we understand what makes these cells more susceptible to physical damage, and perhaps reinforce their structure? When all’s said and done, podocytes form a filter, which has a biological function, but to achieve that function, the podocyte uses a very simple physical mechanism: forming a sieve. So we ask, can we come up with therapeutic strategies that can make the podocytes stronger and more resilient? Or can we identify how specific chemical and biomechanical assaults weaken them? NKI: So is your lab directly looking at ways to fortify the cell? Or is that something you’re laying the groundwork for, for someone else to build from. Dr. Azeloglu: To be able to fortify something, you want to be able to understand it first. There’s been a lot of science over the last two decades showing that a lot of what these cells do is basically prepare for constant physical abuse, for lack of a better word. It’s just not very pleasant to be a podocyte. It’s biologically expensive to try to maintain physical integrity. So “Part One” of my lab’s research program is: to try to understand what makes these cells unique and special, what is the repertoire of these cells for withstanding physical stress. And “Part Two” is: if we can understand it, can we eventually fortify it? Can we prevent this structure from failing under disease conditions? These cells are very fragile, and they need all the help they can get. We’re expecting them to stick around for 80 years — that’s a long time to be under constant physical abuse. Dr. Azeloglu (pictured second from left) and his Systems Bioengineering Laboratory team at the Icahn School of Medicine at Mount Sinai. NKI: The podocyte is such a specific cell—how did you become interested in studying it exclusively? Dr. Azeloglu: Partly because of the video that you’re looking at—they’re really unique. They’re also almost a poster child of physical cellular stamina. They’re a great example of a microscopic structure that has evolved to do a very specialized physical task and do it for an extended period of time. It’s sort of a dream come true for an engineer. NKI: What stage were you at in your research when you received this award? Did it have a big impact on what you were able to do? Dr. Azeloglu: Oh, absolutely! I had just received my appointment as an Assistant Professor, and I had just started setting up my own lab. Without this, I basically wouldn’t have been able to do that. I come from a cardiac background—as a biomedical engineer, I trained in a cardiac biomechanics lab. And the heart, being a mechanical pump, is another example of a living tissue that’s doing a physically demanding job. I studied that for ten years and as I was transitioning into nephrology, the NephCure-ASN Award was critical. It helped me establish myself as an expert in this field as well. It’s sort of a rite of passage—a lot of the fellows who’ve received this award have moved on to successful careers, so it’s almost expected for you to have one to establish yourself in the field. I also think my goals and the goals of the NephCure-ASN Award align very well. I want to understand these cells from an engineer’s perspective, which I think is very relevant to their function, and if we can understand it, I think we’ll be able to cure diseases like FSGS. We’ll be able to not only help patients in terms of their symptoms, but also actually cure the disease. I’m in a pharmacology department, so I know that our standard methods can only help us so far; hopefully, this new, fresh perspective will be able to take us to the next level: instead of just dealing with the symptoms, we’ll be able to cure kidney disease. Hopefully. We were delighted to speak with Dr. Azeloglu on the results of his current research. If you want to stay updated on his work, you can follow him on Twitter (@azeloglu) or visit his lab’s website at http://labs.icahn.mssm.edu/azeloglulab. Thank you for your dedication to this work, Dr. Azeloglu and team! Dr. Evren U. Azeloglu is an Assistant Professor in the Department of Pharmacological Sciences at the Icahn School of Medicine at Mount Sinai. He was originally trained as a mechanical engineer, but later went on to receive his Ph.D. in biomedical engineering from Columbia University. In 2010, Dr. Azeloglu was awarded the Howard Hughes Medical Institute Fellowship from the Life Sciences Research Foundation. His background in biomechanics and systems biology is uniquely positioned to study complex diseases such as hypertension and diabetic nephropathy. He aspires to design transformative therapeutic tools using nanotechnology and tissue engineering.
NephCure Accelerating Cures Institute: Worldwide Launch and US Expansion March 23, 2017 by Lauren Eva The NACI Network is expanding worldwide to speed more effective treatments to individuals with Nephrotic Syndrome Thanks to a significant funding contribution, we’re proud to announce that the NephCure Accelerating Cures Institute (NACI) Care Network is expanding. An investment from Pfizer’s Centers for Therapeutic Innovation (PFE) and Retrophin (RTRX) will help grow the network from 8 sites to 30 sites worldwide. For patients living with Nephrotic Syndrome, more NACI sites means greater access to specialized care and trial opportunities specific to their unique kidney condition. Equally important, a more robust Network gives families across the globe a hub for community building and support at their individual care sites. NephCure Accelerating Cures Institute Global Trials Network The NACI story began in 2014, when leaders from NephCure Kidney International sought advice from leading medical professionals about ways to get better treatment options to patients faster. That following year, NKI launched NACI in partnership with the University of Michigan. Today, NACI is co-led by veteran representatives from NKI in suburban Philadelphia and an expert team from the University of Michigan, Ann Arbor. NephCure Accelerating Cures Institute United States Trials Network To read more about NACI, you can view the full press release here, or visit the NACI website at www.nephcureaci.org. If you have any questions or want to learn more, please send us an email at info@nephcure.org, and we will direct your message to the appropriate party.