L O O S E CONNECTIONS From the Executive Director Shane Robinson...................................................................................... 2 EDNF 2014 Learning Conference Information................................................................................ 4 Applying for Disability Benefits with Ehlers-Danlos Syndrome Ram Meyyappan.................................. 5 Five Myths About Chronic Illness Rachel Stevenson........................................................................... 7 But You Don’t Look Sick Catherine Maire......................................................................................... 10 Interloper in Our Bed Sue Vokral....................................................................................................... 11 “Educating others”............................................................................................................................ 12 Adult Stem Cell Research Shows Promise FDA Consumer Health Information................................. 13 EDNF Conference Kids & Teens Program....................................................................................... 15 Erasing a Genetic Mutation Anne Trafton......................................................................................... 16 Publishing Information.................................................................................................................. 18 Your Magazine About Living With EDS Spring 2014 SPRING 2014 PAGE 2 FROM THE EXECUTIVE DIRECTOR I T’S Spring, and thanks to you EDNF is blossoming! A big part of our mission is EDS awareness and education for physicians and other healthcare professionals. To that end, we’re holding a one-day physicians conference on September 15th at the Greater Baltimore Medical Center (GBMC), in Towson, Maryland. GBMC also hosts the EDNF Center for Clinical Care and Research, so the conference is a great opportunity to launch the Center’s education program which will offer periodic in-person events, as well as distance learning opportunities. Over the last year EDNF has grown by leaps and bounds: a situation that would not be possible without your support. You have donated more, volunteered more, interacted more online, and because of that, EDNF can do more! A few updates from HQ: EDNF Center for Clinical Care and Research at GBMC We continue to fundraise in earnest for the opening of the Center this summer. The ribbon-cutting ceremony is set for the evening of August 16th at the Greater Baltimore Medical Center in Towson, Maryland. The opening of the Center is an incredible milestone in the history of EDNF and the fulfillment of its mission. 2014 Learning Conference As you likely know, this year’s conference will be in Houston, Texas, July 9-11. Some of you may remember that EDNF was in Houston in 2008. Well, we’re back, and this time bigger and better! We’re looking forward to engaging with many EDSers from Texas that haven’t been able to attend the annual conference over the last few years. We’re also very excited to hear from Dr. Brendan Lee who will be updating us on the EDS research he is conducting at Baylor University in Waco, Texas. Join us in Texas for the largest gathering of EDSers in the world! 2014 Physicians Conference A few things we’re working on today: Fundraising Lately, a lot of great things have happened at EDNF, but none would be possible without fundraising. Every day we are actively engaged in pursuing corporate sponsorships and donations, grant-writing, searching for new leads, following-up with past donors, and reaching out to potential first-time donors. We are a public charity, and as such we rely on donations to achieve our mission. Because funding is such a big issue for public charities, we spend a considerable amount of time raising money for our programs and projects. Thankfully, EDNF has a very generous base. Over the last year you have given more, so now we are able to do more. In fact, 2013 was EDNF’s biggest year, and we’re already on track to eclipse it in 2014. We put every dollar to work, so know that your donations are being used for important initiatives like the Center, the new education program we’re going to roll out, and our expanding support network. SPRING 2014 PAGE 3 While we need research and expanded awareness for improved clinical outcomes tomorrow, many people need help today. Each day we’re on the phones, in our email, and on social media helping to link EDSers to the resources that they need. When those resources aren’t available we work to create them whenever possible. Backed by our world-class Professional Advisory Network and our tireless volunteers we are committed to supporting you. to disburse a significant amount of funding through grants towards coordinated, focused, and meaningful research projects. Support Strategic planning It goes without saying that we spend a lot of our time planning for the future. We can’t beat EDS without planning. Our allvolunteer Board of Directors meets quarterly to ensure that EDNF is on track, with periodic committee meetings during the interim. Our Board Members will be at the Learning Conference in Houston if you would like to meet them. Global reach If you’ve ever been to an EDNF Learning Conference you already know that our membership is global, but we can do more than that. By partnering with other EDSrelated organizations around the world we can create a synergy that will benefit all of us. To that end, Ehlers-Danlos Support UK will be at our upcoming conference to meet with our Board of Directors, and that’s only the beginning! As you can see, we’ve been busy, but if it weren’t for you and the support that you’ve given EDNF, then none of this would be possible. Thank you, and please don’t hesitate to contact us. We love hearing from you. Shane Robinson Executive Director, EDNF Some things we’d like to work on tomorrow: A network of centers Right now we’re very focused on the EDNF Center for Clinical Care and Research at GBMC. It’s imperative that we get it right, and we will, but what comes next? Quite possibly a network of centers with the end goal of top quality EDS care at every major medical institution. We’re working towards a day when you can expect quality care at whatever hospital you enter. A large endowment for research Research is costly, so we haven’t been able to fund a lot of it, and what we have funded has been sporadic. We envision a large endowment which would enable us “It isn’t good to hold on too hard to the past. You can’t spend your whole life looking back. Not even when you can’t see what lies ahead. All you can do is keep on keeping on, and try to believe that tomorrow will be what it should be — even if it isn’t what you expected.” — Jim Butcher SPRING 2014 PAGE 4 2014 Learning Conference Hilton Americas Hotel § Houston, Texas § July 10–12 Early registration open until May 6! Sam Bailey, MS, CGC John Belmont, MD, PhD Lara Bloom Heather Butler-Pierce Heidi A. Collins, MD Shweta Dhar, MD, MS, FACMG Dr. Epps Clair Francomano, MD Erin Grigsby Fraser Cummins Henderson Sr., MD Imad Jarjour, MD, FAAN, FAAP r. Diane Lebron D Dr. Brendan Lee Dr. Ann Maitland John Mitakides, DDS, DAACP, EDJ, PAN Shaine Morris, MD, MPH Sandesh Nagamani, MD, FACMG Derek Neilson, MD Jonathan Parr Alan Pocinki, MD Professor Rodney Grahame Brad Tinkle, MD, PhD Shani Weber Please note that the speakers listed are subject to change. Thursday will consist of physician consultations beginning in the early afternoon; a special session by Dr. Brendan Lee; and a welcome reception for all conference attendees that evening. Friday and Saturday will consist of educational sessions all day, concluding with Saturday night's banquet. www.ednf.org/conference SPRING 2014 PAGE 5 APPLYING FOR DISABILITY BENEFITS WITH EHLERS-DANLOS SYNDROME S EVERE symptoms and long term complications of this Ehlers-Danlos syndrome can prevent you from working and can potentially qualify you for Social Security Disability (SSD) benefits, though you will need to prove your condition prevents you from working in a job in which you can earn a gainful living in order to receive benefits. Medically Qualifying for SSD To get SSD, you must suffer from a severe medical condition that can either: be proven to have been present for at least 12 months Section 1.02 – major dysfunction of a joint Sections 2.02, 2.03, 2.04 – vision loss or impairment Section 4.02 – aortic aneurysm Section 5.02 – bleeding in the gastrointestinal system that requires blood transfusions Section 8.04 – chronic skin infections It is important to understand that you do not have to meet any of these listings exactly in order to be eligible for benefits. Your medical records and disability application must simply show: OR which is expected to prevent you from working for at least that long. Additionally, the Social Security Administration (SSA) must see that you are unable to maintain employment in any position for which you would otherwise be qualified. This means you need to show through thorough medical records that your everyday abilities are severely limited by Ehlers-Danlos. The SSA will review your medical records under listings in the Blue Book, which is a manual of impairments and the medical evidence necessary for proving disability with each condition, though there is no dedicated listing for Ehlers-Danlos. Because the syndrome can affect multiple body systems, the SSA may need to review any or all of the following listings when evaluating your medical records and disability application: your Ehlers-Danlos syndrome is equal in severity to a listed condition OR your “residual functional capacity” (RFC) is so limited that you are unable to maintain gainful employment even though you do not exactly meet or closely match a listed conditions. While in some circumstances it is possible to continue working and get disability benefits, in order to qualify medically through and RFC analysis, the SSA will need to determine that you are so severely affected by Ehlers-Danlos on a daily basis that it prevents you from working in any job at all, even a light work, sedentary, or administrative position. The SSA’s Disability Programs If you are found medically eligible for benefits, you may be able to get SSD through both of the SSA’s disability programs; however, there are technical and financial eligibility rules you must meet for each program. SPRING 2014 PAGE 6 For Social Security Disability Insurance (SSDI), which is designed to pay benefits to disabled workers, you must have sufficient work credits from your previous employment in order to receive benefits. You can learn more about SSDI here: http://www.disabilitybenefits-help.org/ssdi/qualify-for-ssdi For Supplemental Security Income (SSI), which is a need-based program designed to pay benefits to disabled individuals who have very limited income and other financial resources, you must not exceed the threshold for monthly finances set by the SSA, which is $740 per month for 2014. The calculation of “available” income and resources is a bit complex though. You can learn more about SSI here: http://www.disability-benefits-help. org/ssi/qualify-for-ssi Submitting an Application Applications for SSDI can be completed online via the SSA’s website, but SSI applications must be made in person at your local SSA office. You can schedule an appointment to complete both applications in person by calling 1-800772-1213, or you may decide to file for SSDI online and follow-up locally to submit your medical and other supporting documentation and to apply for SSI. Either way, you must ensure you thoroughly complete all the required forms and that you support your claim with extensive medical records and any other documentation that prove your Ehlers-Danlos syndrome is indeed severe enough to prevent you from earning a living. Ram Meyyappan eHlErs-dAnlOS sYnDroMeS aWaRenEsS mOntH mAY 2014 NeVER aLoNE events and information throughout our communities SPRING 2014 PAGE 7 FIVE MYTHS ABOUT CHRONIC ILLNESS THAT ARISE FROM HEALTHY PEOPLE’S INHERENTLY DIFFERENT PERSPECTIVE How unwitting assumptions on your part may alienate good people in bad situations. Addressed to those without chronic illness, from an EDSer’s perspective. Myth�One Sick people must be ignorant about, or resisting, good medical advice that you can provide, so you should tell them about it right away. It’s completely possible you know a health tip that we’ll be interested in adding to our (likely already vast and varied) health care program, but advice shouldn’t be your first response when you hear we have a problem. You think you’d love to hear this advice yourself, and tout suite! We’d rather you hear and understand us first, because we will likely tell you how you can help us best. The assumption that you know what will help can feel to us that you are invalidating our autonomy to make healthrelated choices. We’ve probably waded through a lot of good and bad treatments, maybe already including your suggestion, and we need to keep a watchful eye that our time and rapidlyconsumed health funds aren’t thrown away on high-risk or low-reward ideas. Some of your advice might come from more immediate and short-term concern for us. You might want to encourage us to rest right now, or try to motivate us to exercise this afternoon. It can feel to us that you’re doubting our ability to set our own limits and goals, and to know how our immediate decisions fit into a broader context (for instance, deadlines for which we need to push through, or that a work-out now could set us back further with an injury). Trust that our root problem is physical and not something curable by “mind over matter.” For most of us, our problem has never been in our ability to power through the pain, motivate ourselves, or do what’s best for our bodies; these are actually some of our greatest strengths and have been honed with years of practice. Myth�Two Sick people must like using mobility equipment, needing help, and hearing “sympathy.” We typically hate these things. You may have had a sports injury once, and perhaps you enjoyed using a wheelchair, having your friends rally around you on your way to the dining hall. It was novel for you, but it was not something you required because of a serious, and confidence-deflating, failing of your body. People with chronic illness have learned to value the activities we can do by ourselves, and to appreciate the times when we can be better able-bodied. We relish every possible opportunity to do what we can, but we sometimes push past medically advisable limits when we’re frustrated or feel we’re being judged for using support. We may feel even more judged if you find us SPRING 2014 PAGE 8 “suspicious” for using a variable amount of support on different days. Chronic illnesses don’t respond to treatment linearly and curatively like a sports injury usually would to physical therapy, so the amount of support needed will vary by day for us. It may look to you like we’re just being wimpier on certain days or seem to you as though we’re faking it on those days, but we’re actually proportionally accommodating a greater physical need. Regarding sympathy, you might have liked hearing people’s commiseration while recovering from an acute injury. However, to a self-conscious chronically ill person hearing it day in and day out, it often sounds like sarcasm meant to criticize our management of a condition, or a sign that you see us differently than we see ourselves and would like to be seen. Myth�Three Sick people are diagnosing themselves, stockpiling diagnoses, or “doctor shopping.” Usually corollary to those myths are the assumptions that we don’t really have these conditions and that we somehow infiltrated the chronic illness community because we really like to see doctors, learn about disease, and identify with a condition. You think we’re just trying to find some way to be different than you? We were probably just like you before we heard our diagnosis. We liked to think we would become different in fun ways — we’d become president or be able to open beer bottles with our teeth. Who knows, we still might be able to cultivate these differences. But now, we also have to come to accept more challenging differences; we have to start learning boring details about how our bodies are functioning differently than yours, and then spend most of our time at different medical specialists to correct for those differences, which is not fun for anyone. If you think we know a “suspicious” amount of information about a rare medical condition, as if we’ve been memorizing the symptoms to pretend we have them, it’s — you’ll never guess — because a doctor proved extensively to us that we have that medical condition. So, of course, we now know a lot about it! We may have more than one diagnosis, but that’s perfectly explainable as well. Our root biological problem may have manifested in multiple systems, or our time with all these doctors may have secondarily allowed them to detect additional problems common even in healthy populations. Your doctors wouldn’t be as likely to pick up on those other problems in you because you only need to visit them rarely and then only briefly. We’re also more likely to visit more doctors or to switch doctors more often. We want to get second opinions until they form a consensus. We want to treat our multi-system effects with appropriate specialists. We want to find the doctors that will make up the best long-term care team we can assemble. Myth�Four Sick people are needy or bossy, and have no consideration for what other people do for them. We might appreciate your help more than healthy people would. For example, carrying something or walking to get something can seem like a really big deal to those of us who can’t accomplish that thing ourselves. We may feel even ashamed to ask for your help, because we know we’d be forcing you to look inconsiderate if you said no. Go ahead and say “no” when you need to — your time is important to us! But know that saying “yes” is doing us actual physical benefit, and is not just placating a lazy whiner. Denying us help is not a valid medical treatment to make us recover faster by not letting us “wallow” (see Myth Two — we SPRING 2014 PAGE 9 practically never want to wallow). If we use short-tempered or presumptuous language, talk it out with us. A seemingly ungrateful tone may actually be frustration about not being able to accomplish a task without bothering anyone, frustration that we need to smile and rely on others at a time when we might rather be alone, or a necessary forcefulness about the seriousness of the request (e.g., a hurried, “No, don’t sit with me!” to a considerate helper is this EDSer’s abbreviation for “depressing this shared couch cushion will make my hip pop out of its socket!”). Myth�Five Sick people complain out of proportion to their problem. Well yes, it is sometimes out of proportion; in most cases, it’s much lower than you’d complain about the same problem. We get sick of hearing ourselves complain so much, too, but it’s sometimes the tip of the iceberg of what we’re dealing with. There exists what I call a “complaint quota” in any social situation. We try to not exceed that quota ourselves, and we’ll likely let you fill a larger proportion of it because we know how much it sucks to have a complaint belittled. Complaining has a purpose. Everyone, everywhere, wants to hear the solidarity evoked by a good complaint, to help us shoulder life’s loads. To us in the chronic illness community, it has additional purposes; it is us, quite necessarily, self-advocating for our medical needs and raising awareness. But a good conversation involves give and take, and it would be one-sided and boring to us if we filled up the quota by ourselves. So complain with us! Sometimes our human pettiness can come out, and we’ll single out one of your complaints that we think carries more weight than ours would be allowed to, and we might say something like, “Oh come on, it’s not that bad.” Don’t let us get away with that. All people deserve to complain about little things once in a while, and we ourselves can “sweat the small stuff” sometimes, too. Also note that, occasionally, we actually would rather not talk about our condition and you end up kind of forcing it out of us. As long as there is a culture where your initial response to seeing crutches or a wheelchair is, “Oh, no, what did you do to yourself?” — which we might see as prying, dismissive, or victimblaming, by the way — we’re going to have to tell you why that question isn’t accurate. This isn’t a klutzy thing we did to ourselves, nor the funny or heroic sports story you were hoping to hear. The answer might not be short, or the short answer might make you think we’re something we’re not, so we’d often rather tell you the long, whiny-sounding, accurate version. And we can promise that this real answer will make you look at life a little differently. Rachel Stevenson Please be gentle with each other; who knows how each of us got where we are? One can make absolutely the best decision at every step along the path, and still find oneself lost. SPRING 2014 PAGE 10 BUT YOU DON’T LOOK SICK How did I end up here in a body of softly curved joints and misplaced bones that cannot sleep at night? She checks off symptoms one by one more accurate than any form at any of the hundred doctors with any of their hundred tests. The knock-kneed child never does a pull up, never runs a mile, never climbs a tree. but she can bend her body round like Gumby, and pour salt on her food like sand on a desert. It is a slow dissolving: loosening body from bones. The teenager with the stomach problem, bruises, migraines, tiredly struggles to fit in, keep up, gives up, ends up in a room with books and darkness. The woman can’t open jars. “A delicate flower,” her husband calls her. He compensates, helps out when pain puts her in her bed. One physical therapist has a thought. A disease the woman’s never heard of. Her life’s history in a Wikipedia entry. “Rate your pain from one to ten,” they say. She laughs. Impossible. They have no idea. Catherine Maire SPRING 2014 PAGE 11 INTERLOPER IN OUR BED When did it really happen? Was a line drawn in the sand? Did he blow in on a chilling breeze, Or creep across the land? Don’t let him drive a wedge between us, Afraid to just reach out. Don’t let him trap me by myself, Not hear me crying out. And how was it alright he stayed? He claimed a place to live… He’d take and take and take some more, And never would he give. I’m wounded in ED’s last assault, Fight or flight keeps me alive. Injured, scarred, a damaged heart, For us I will survive. He tried to make me leave you, And lure me far away — With pain and illness, loss and sadness, But - I fought hard to stay. I choose to live my life with you, The man you’ll always be. I push back hard to keep away, My predicted destiny. You feel him in our lives, I know, He’s here, ED’s here to stay. He’s the interloper in our marriage, And he wants to get his way. Sue Vokral So, as we lie in bed each night, Lonely sheets that fill the gap. Are we strong enough to just reach out, Or fall into ED’s trap. He wants me for himself you know, Culled from the healthy herd. A lone female looking for her mate, Her cries that go unheard. SPRING 2014 PAGE 12 Educating others Helping other zebras Letting others help Evaluating priorities Remaining ‘flexible’ Strengthening and stabilizing Developing a new plan for life Accepting life as it is Never giving up Looking for patterns Organizing life day by day Striving to be a fighter Sharing what works Yearning for more information Napping as necessary Discovering tools for coping Rationing out spoons Optimistic about tomorrow Modifying situations Encouraging other zebras SPRING 2014 PAGE 13 ADULT STEM CELL RESEARCH SHOWS PROMISE S CIENTISTS sporting white coats and safety gloves are working in a bright Food and Drug Administration (FDA) lab on an incredible project. They are part of FDA’s MSC Consortium, a large team of FDA scientists studying adult mesenchymal stem cells (MSCs) — cells that could eventually be used to repair, replace, restore or regenerate cells in the body, including those needed for heart and bone repair. The scientists’ investigational work is unprecedented: Seven labs at FDA’s Center for Biologics Evaluation and Research formed the consortium to fill in gaps in knowledge about how stem cells function. “This research aims to facilitate development of this important class of innovative medical products,” explains Carolyn A. Wilson, Ph.D., associate director for research at the center. “It’s the first time we’ve done anything like this, and it’s proven to be a very useful approach. It’s worked so well because this is a huge, complicated project that requires expertise in many different technologies and methods.” The research could ultimately be key to the advancement of personalized medicine, the practice in which medical treatment is tailored to the needs of an individual patient. “It’s not science fiction,” says Steven R. Bauer, Ph.D., chief of the Cellular and Tissue Therapy Branch in FDA’s Office of Cellular Tissue and Gene Therapies. “For me, regenerative medicine is the most exciting part of what we regulate in our office.” So What Are Stem Cells? There are two basic kinds of stem cells that are currently useful in the field of regenerative medicine: multipotent and pluripotent stem cells. Multipotent stem cells are generally taken from adults and can divide and develop into many different cell types. Pluripotent stem cells can develop into any type of cell in the body. Both types could divide to replenish cells damaged by injury, illness or normal wear. When stem cells divide, the new cells can either remain stem cells or develop into a new type of cell with a more specific function. Two types of pluripotent stem cells exist: human embryonic stem cells and induced pluripotent stem cells, which are created by reprogramming adult cells that had already changed into a mature type of cell. FDA’s MSC Consortium is not studying stem cells taken from embryos. “We’re looking at a particular kind of multipotent adult stem cell — the MSC — which is being used in a lot of regenerative medicine clinical trials,” adds Bauer. The group is currently studying eight unique cell lines, each acquired from commercial sources and sourced to one of eight distinct, adult donors. (Males and females age 22 to 47 donated stem cells from bone marrow.) The cells under study are multipotent: “They can differentiate (mature into) at least three cell types: bone, fat and cartilage, primarily,” Bauer explains. “They can also differentiate into nerve cells, liver cells and a kind of cell called ‘stroma’ that is in the bone marrow and supports blood forming cells. Then, for investigational clinical SPRING 2014 PAGE 14 uses, they’ve been used for repairing hearts, repairing bone and repairing cartilage.” Why Is FDA Studying These Cells? In addition to differentiating into a variety of replacement cell types, MSCs can limit a patient’s immune response. So they can potentially be taken from one human donor and placed into a different recipient with less possibility of rejection. But growing stem cells and making sure they are safe and effective is challenging, which is one reason why stem-cell based clinical trials have not yet resulted in a marketed product. liquid solution and grown in sterile containers called tissue culture flasks. Cells then multiply and go through three, five or seven generations of growth. FDA scientists are using a variety of cuttingedge methods to characterize cells and then determine if any of these characteristics can predict the behavior of the cells in biological assays or in animal models. The next step will be to determine if any characteristics they measure will predict the safety or effectiveness of stem-cell based products in patients. Specifically, scientists will continue studying whether factors such as different methods of growing the cells, donor age or gender affects “The major challenge is that cells are much more the cells’ quality and performance. This research complex than traditional products that FDA will ultimately provide new tools to the regulates. And they have the ability to respond community of academic and private industry to their environment,” scientists who are Bauer explains. “Taking interested in evaluating them out of the body and developing stem “…including the ability and manufacturing cells into new clinical to repair or even replace them — that is, growing treatments. large numbers of organs and tissues more them — or isolating “The consortium has them can change their shown that widely safely and effectively biology. And it can accepted ways to identify change the way they and characterize MSCs than traditional means.” behave if they are put do not reveal some back into the patient.” important biological differences between batches of these cells,” Bauer For instance, if cells are manufactured in large says. So the consortium seeks to demonstrate quantities outside their natural environment, ways to better characterize MSCs that will be they may become ineffective or develop used in clinical trials. That’s important because, harmful characteristics. For example, they can if investigators can improve the tools used to produce tumors, severe immune reactions or characterize MSCs used for clinical trials, the growth of unwanted tissue. So FDA is trying to data generated from their studies could also develop methods that would predict with more improve because their MSC products will be certainty how manufactured or isolated adult more predictable, he adds. stem cells will behave in patients. And the improved predictability of their What’s Being Done? products will, in turn, allow FDA scientists to more easily evaluate the safety and effectiveness In the labs, cells are suspended in a nutrient of new stem cell technologies — a key part of SPRING 2014 PAGE 15 the regulatory science that is the foundation of FDA decisions. Agency scientists already have published six papers in scientific journals such as Tissue Engineering and Cytotherapy. “We’re hoping this project will inspire people to do more research in this area,” Bauer says. Stem cells, like other medical products intended to treat, cure or prevent disease, require FDA approval before they can be marketed. “It is important for FDA to maintain a sound regulatory science research program to promote the development of safe and effective products in emerging areas that hold great promise,” Bauer says. “My colleagues and I hope our scientific findings will be helpful in the field of regenerative medicine, including the ability to repair or even replace organs and tissues more safely and effectively than traditional means,” he adds. “Although there are many scientific hurdles to overcome before the use of stem cells reaches its full potential, I think this medicine will eventually have the capacity to do that.” FDA Consumer Health Information U.S. Food and Drug Administration Find this and other Consumer Updates at www. fda.gov/ForConsumers/ConsumerUpdates Sign up for free e-mail subscriptions at www.fda. gov/consumer/consumerenews.html EDNF CONFERENCE KIDS & TEENS PROGRAM T HIS year's Kids & Teens program will serve children and teens ages 5–15 years old. The EDNF Learning Conference will provide developmental curriculum, activities, games, and educational sessions with doctors and other related speakers. While we will focus on encouraging the children, teens and students to gain a deeper understanding of EDS, we will also provide opportunities for them to have fun, and gain some deeper relationships with children and teens from all over the country! A strong focus this year will be about inspiring a better future with greater possibilities. The 2014 Learning Conference will offer a new track of sessions with focus on teens and young adults. These sessions will provide a comfortable environment for young adults to meet with doctors and other inspirational individuals while they get to know one another in a more personal setting. We will also have a teen/young adult lounge where they can relax, play some games and work on other activities at their leisure. SPRING 2014 PAGE 16 ERASING A GENETIC MUTATION MIT TEAM REVERSES A LIVER DISORDER IN MICE BY CORRECTING A MUTATED GENE U SING a new gene-editing system based on bacterial proteins, MIT researchers have cured mice of a rare liver disorder caused by a single genetic mutation. The findings, described in the March 30 issue of Nature Biotechnology, offer the first evidence that this gene-editing technique, known as CRISPR, can reverse disease symptoms in living animals. CRISPR, which offers an easy way to snip out mutated DNA and replace it with the correct sequence, holds potential for treating many genetic disorders, according to the research team. “What’s exciting about this approach is that we can actually correct a defective gene in a living adult animal,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering at MIT, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the paper. The recently developed CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this cellular system to create geneediting complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut. At the same time, the researchers also deliver a DNA template strand. When the cell repairs the damage produced by Cas9, it copies from the template, introducing new genetic material into the genome. Scientists envision that this kind of genome editing could one day help treat diseases such as hemophilia, Huntington’s disease, and others that are caused by single mutations. Scientists have developed other gene-editing systems based on DNA-slicing enzymes, also known as nucleases, but those complexes can be expensive and difficult to assemble. “The CRISPR system is very easy to configure and customize,” says Anderson, who is also a member of MIT’s Institute for Medical Engineering and Science. He adds that other systems “can potentially be used in a similar way to the CRISPR system, but with those it is much harder to make a nuclease that’s specific to your target of interest.” Disease correction For this study, the researchers designed three guide RNA strands that target different DNA sequences near the mutation that causes type I tyrosinemia, in a gene that codes for an enzyme called FAH. Patients with this disease, which affects about 1 in 100,000 people, cannot break down the amino acid tyrosine, which accumulates and can lead to liver failure. Current treatments include a low-protein diet and a drug called NTCB, which disrupts tyrosine production. In experiments with adult mice carrying the mutated form of the FAH enzyme, the researchers delivered RNA guide strands along with the gene for Cas9 and a 199-nucleotide DNA template that includes the correct sequence of the mutated FAH gene. SPRING 2014 PAGE 17 Using this approach, the correct gene was inserted in about one of every 250 hepatocytes, the cells that make up most of the liver. Over the next 30 days, those healthy cells began to proliferate and replace diseased liver cells, eventually accounting for about one-third of all hepatocytes. This was enough to cure the disease, allowing the mice to survive after being taken off the NCTB drug. “We can do a one-time treatment and totally reverse the condition,” says Hao Yin, a postdoc at the Koch Institute and one of the lead authors of the Nature Biotechnology paper. “This work shows that CRISPR can be used successfully in adults, and also identifies several of the challenges that will need to be addressed moving forward to the development of human therapies,” says Charles Gersbach, an assistant professor of biomedical engineering at Duke University who was not part of the research team. “In particular, the authors note that the efficiency of gene editing will need to improve significantly to be relevant for most diseases and other delivery methods need to be explored to extend the approach to humans. Nevertheless, this work is an exciting first step to using modern gene-editing tools to correct the devastating genetic diseases for which there are currently no options for affected patients.” To deliver the CRISPR components, the researchers employed a technique known as high-pressure injection, which uses a highpowered syringe to rapidly discharge the material into a vein. This approach delivers material successfully to liver cells, but Anderson envisions that better delivery approaches are possible. His lab is now working on methods that may be safer and more efficient, including targeted nanoparticles. Wen Xue, a senior postdoc at the Koch Institute, is also a lead author of the paper. Other authors are Institute Professor Phillip Sharp; Tyler Jacks, director of the Koch Institute; postdoc Sidi Chen; senior postdoc Roman Bogorad; Eric Benedetti and Markus Grompe of the Oregon Stem Cell Center; and Victor Koteliansky of the Skolkovo Institute of Science and Technology. Anne Trafton MIT News Office The research was funded by the National Cancer Institute, the National Institutes of Health, and the Marie D. and Pierre Casimir-Lambert Fund. SPRING 2014 PAGE 18 L O O S E CONNECTIONS The Magazine About Living With EDS PUBLISHED BY Professional Advisory Network Heidi Collins, MD, Chair Patrick Agnew, DPM Peter Byers, MD Edith Cheng, MD FOUNDER Nancy Hanna Rogowski 1957–1995 Executive Director Shane Robinson Board of Directors Sandra Aiken Chack, Chair Judge Richard P. Goldenhersh, Vice Chair Richie Taffet, MPH, Secretary Richard Malenfant, CPA, Treasurer Elliot H. Clark, Chair Emeritus Heidi Collins, MD Clair Francomano, MD Susan Hawkins Deb Makowski Linda Neumann-Potash, RN, MN, CBN Janine Sabal John Zonarich, Esq. To contact EDNF, email [email protected]; write to Ehlers-Danlos National Foundation, 1760 Old Meadow Road, Suite 500, McLean, Virginia 22102; or call (703) 506-2892. 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