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CMTA WINTER 2021 THE Re p o r t www.cmtausa.org MEET CRYSTAL EMERY— WRITER/PRODUCER/FILMMAKER 7 > Two Studies on Inhibiters Funded 20 > It Starts With the Toes… 31 > Like Father, Like Son
CMTA LEADERSHIP Amy J. Gray, CEO BOARD OF DIRECTORS ADVISORY BOARD CMTA STAR ALLIANCE Gilles Bouchard, Chairman Teresa Carroll, MS, PhD PA RT N E R S : Gary Gasper, Treasurer Gregory Carter, MD, MS Herb Beron, Secretary Ken Cornell, CO Dan Chamby Bob DeRosa ACCELERON PHARMA David Coldiron Katy Eichinger, PT, DPT, NCS Thomas W. Dubensky, Jr., PhD Ashraf Elsayegh, MD, FCCP ARQ GENETICS Laura Fava Tim Estilow, OTR/L Alan Korowitz Shawna Feely, MS, CGC CHARLES RIVER David Norcom Valery Hanks, OTR/L, C/NDT Steve O’Donnell Sarah Kesty GENZYME, A SANOFI COMPANY Chris Ouellette Kate Lair Elizabeth Ouellette Bethany Noelle Meloche HUMANFIRST THERAPEUTICS LLC Kevin Sami Tom Meloche Phyllis Sanders, Esq. David Misener, BSc (HK), CPO, MBA HORIZON DISCOVERY Steven Scherer, MD, PhD Michael Shy, MD Elizabeth Misener, PhD, LMSW Christine Murray, MD IONIS PHARMACEUTICALS John Svaren, PhD James Nussbaum, PT, PhD, SCS, EMT Special Advisor to the Board Sabrina Paganoni, MD, PhD Glenn Pfeffer, MD INFLECTIS BIOSCIENCE Bruce Chizen Kenneth Raymond Clark Semmes THE JACKSON LABORATORY STAR ADVISORY BOARD Carly Siskind, MS, CGC John Svaren, PhD, Chair, Scientific Expert Board Greg Stilwell, DPM NCATS (NIH) Mark Scheideler, PhD, Chair, Therapy Expert Board David Tannenbaum, LCSW Michael E. Shy, MD, Co-Chair, Clinical Expert Board Amy Warfield, PT, DPT NEW YORK STEM CELL FOUNDATION Mary Reilly, MD, Co-Chair, Clinical Expert Board Evan Zeltsar PASSAGE BIO PSYCHOGENICS CMTA STAFF Jonah Berger National Youth Programs Manager, jonah@cmtausa.org REGENACY PHARMACEUTICALS Kim Magee Director of Finance and Administration, kim@cmtausa.org Leslie Nagel Marketing Coordinator, leslie@cmtausa.org RENOVO NEURAL, INC. Laurel Richardson Director of Community Outreach, laurel@cmtausa.org Jeana Sweeney Director of Development, jeana@cmtausa.org CMTA CORPORATE PA RT N E R S : AETREX WORLDWIDE, INC. ALLARD, USA BALANCE WALKING FOOT SOLUTIONS GENEDX HANGER CLINIC KINETIC RESEARCH TURBOMED ORTHOTICS Walking Together Apart page 9 CMTARe p or t THE INSIDE THIS ISSUE: RESEARCH Board Approves Grants for Inhibitor Work .............7 Marcia Semmes Executive Editor Karlyn Rosen Aires Designer CMT STORIES Dana Schwertfeger Contributing Editor Filmmaker Doesn’t Let CMT Stop Her ......................6 The CMTA Report is published by the Educator Seeks Input..............................................19 Charcot-Marie-Tooth Association, a registered Widower Makes/Sells Pens for CMTA ....................25 non-profit 501(C)(3) health organization. © 2021, The CMTA. All rights reserved under Former Pastor Spreads Word About CMT ..............28 International and Pan American Copyright conventions. No part of this newsletter may LIVING WITH CMT be reproduced in any form or by any COVID-19 Vaccine ....................................................4 electronic or mechanical means, including information storage and retrieval systems, New Genetic Tools for Family Planning ................10 without permission in writing from the Foot Surgery Part 4 ................................................20 publisher. The opinions expressed in the newsletter are not necessarily those of the CMTA COMMUNITY Charcot-Marie-Tooth Association. The material is presented for educational purposes only New Advisory Board Members .................................8 and is not meant to diagnose or prescribe. Why I Give: Howard Landis.....................................14 Always consult your professional advisers New Centers of Excellence .....................................16 as to how medical, legal or financial information in The CMTA Report pertains to Patient/Family Conference Zoomed .......................23 you. The CMTA assumes no liability for any OUR MISSION: To support the development of information in The CMTA Report. FUN AND FUNDRAISING new drugs to treat CMT, to improve the quality of life Walks 4 CMT Raised $180,000 .................................9 ISSN #1067-0181 Vol. 36, No. 1 for people with CMT and, ultimately, to find a cure. CMTA YOUTH Email the CMTA at OUR VISION: A World Without CMT. Youth Council Gears Up Fundraising......................12 info@cmtausa.org
A M E S S A G E F R O M T H E C E O DEAR FRIENDS, I’m sure I’m not the only one who was happy to see 2020 end. It’s more than a little ironic that a number depicting clarity of vision came to represent a year filled with confusion bordering on chaos. But with your help, the CMTA not only persevered, it thrived. The CMTA community thrived because our members share our passion for our mission—finding a cure for CMT. The pandemic did nothing to diminish that passion—though it did force us to pivot to new ways of holding branch meetings, walking 4 CMT and shifting to research that could be done in a bubble. But, as David Tannenbaum noted in our special issue on COVID-19, people with CMT have had to deal with strangeness and adversity all of their lives. According to David, “The uncertainty and fear of the COVID-19 crisis is not all that different from the uncertainty and fear we face in living with CMT.” This issue is dedicated to everyone—men, women and children, teachers, doctors and writers—who is helping the CMTA by spreading the word about CMT. It’s a constant, ongoing battle to educate the many, many people who still have not heard of the disease. But it’s a vital step toward finding a cure—identify the problem, make people aware of the problem and ask people to help fund a cure. Dave Loy got a massive shark tattoo on his arm so that he can talk to people about CMT when they ask about it. Rick Clemente makes and gives away gorgeous wooden pens. When people ask about the pens, he says the price is a donation to the CMTA. Sarah Kesty entered her lesson plan about CMT into a contest, and Jeff Seitzer is publishing his memoir about CMT. Filmmaker Crystal Emery tells us how she prevails over her CMT despite its impact on her arms, legs and respiratory system. We’ll be bringing you more in-depth information on STAR’s progress in an upcoming special issue, but for now I’d like to highlight a few examples of the tremendous research progress made in 2020, including: • $2.5 million invested in research • 19 joint preclinical treatment studies this year with leading pharma/biotechs developing treatments for CMT • 32 total alliance partners from top biotech, pharma and gene therapy labs around the world • 50 active research projects and studies and eight more projects approved in recent months • More than 30 of the leading CMT scientists and gene therapy experts from around the globe working with our STAR Advisory Board • Research tools for biotech companies to use in testing potential therapies for types CMT1, CMT2, CMT4 and CMTX • Investments in the discovery of new genes that cause CMT We look forward, as always, to a brighter future for everyone with CMT. And we wish each of you a very Happy New Year. With warm regards, AMY GRAY, Chief Executive Officer WINTER 2021 THE CMTA REPORT 3
COVID-19 Vaccine and CMT—Q & A Pfizer/BioNTech vaccine did not new smartphone-based, after- mention any contraindications for vaccination health checker for What are the side effects of genetic therapies or other med- people who receive COVID-19 the COVID vaccine? Will they The known side effects of cur- ications particularly important to vaccines. affect my CMT? rent and likely-to-be authorized the CMT community, but you COVID-19 vaccines are similar to should consult your clinician those of the annual flu shot and about whether the vaccine will How long will it take to work? include muscle soreness at the have an adverse impact on any You won’t get the full protection Will I get proof of vaccination? injection site, fever, tiredness, future course of treatment. from the Pfizer-BioNTech vac- body aches and headache. It’s Should there be any contraindica- cine until about a week after the important to note that at this tions in the future, we will update second dose, based on clinical time we do not know whether or our information accordingly. trial data. The researchers found not the COVID-19 vaccine will that the vaccine’s protection have a different or more serious started to emerge about 10 days set of side effects for CMT after the first dose, but it only What safety measures are in patients. You should talk to your The U.S. vaccine safety system reached 52 percent efficacy, place for the COVID vaccine? doctor about that possibility. ensures that all vaccines are as according to a report in the New safe as possible. The Centers for England Journal of Medicine. A Disease Control has developed a week after the second dose, the new tool, v-safe, as an additional efficacy rose to 95 percent. You What impact will the vaccine layer of safety monitoring to should receive a vaccination card have on possible future gene increase our ability to rapidly or printout that tells you what therapy treatments or The Food and Drug Admini- detect any safety issues with COVID-19 vaccine you received, medications? stration’s authorization of the COVID-19 vaccines. V-safe is a the date you received it and 4 THE CMTA REPORT WINTER 2021
where you received it. You by the virus itself. Health offi- should receive a paper or elec- cials will investigate each event FOR MORE INFORMATION about tronic version of a fact sheet that to see if it’s simply coincidence— the COVID-19 vaccine and CMT, tells you more about the specific or if it could have been caused COVID-19 vaccine you are being by the vaccine. While everyone go to www.cmtausa.org/covid. offered. Each authorized COVID- should be prepared to hear 19 vaccine has its own fact sheet about these reports, they should immune response in older peo- that contains information to help not be a cause for worry or ple, it’s possible that one of the you understand the risks and prompt you to delay getting the new vaccines could emerge as a benefits of receiving that specific vaccine. Your risk of severe com- better option for this age group. vaccine. plications from COVID-19 is far It’s just far too soon to know. higher than your risk of compli- What if I forget to get the cations from the vaccine. Will these vaccines put a dent The coronavirus vaccines will be in the epidemic? Both the Pfizer-BioNTech and second dose on time? Moderna vaccines have two much less effective at preventing I’ve had COVID-19 already. doses, with the booster shot It’s safe, and probably even bene- death and illness in 2021 if they Do I need the vaccine? coming a few weeks after the ficial, for anyone who has had are introduced into a population first. Pfizer-BioNTech’s second COVID to get the vaccine at some where the virus is raging—as is dose comes three weeks after the point, experts said. Although peo- now the case in the U.S. A vac- first, and Moderna’s comes four ple who have contracted the virus cine that’s 95 percent effective, weeks later. The second dose do have immunity, it is too soon as Moderna’s and Pfizer’s ver- provides a potent boost that to know how long it lasts. So for sions appear to be, is a powerful gives people strong, long-lasting now, it makes sense for them to fire hose. But the size of a fire is immunity. If for some reason get the shot. The question is still a bigger determinant of how you fail to get the second shot when. Some members of the CDC much destruction occurs. precisely three weeks after the advisory committee have sug- According to the authors of a first, you don’t have to start all gested people who have had paper in the journal Health over again with another two- COVID in the past 90 days should Affairs, at the current level of dose regimen. be toward the back of the line. infection in the U.S. (about 200,000 confirmed new infec- tions per day), a vaccine that is 95 percent effective—distributed What will happen if serious Will the vaccine work on All the evidence so far suggests at the expected pace—would still side effects crop up after the older people? Once a vaccine starts to reach that the answer is yes. The clini- not be enough to end the terrible vaccine is rolled out? large numbers of people, it’s cal trials for the two leading toll of the virus in the six months possible (and not uncommon) vaccines have shown that they after it was introduced. Almost for a small number of severe work about the same in older 10 million or so Americans “adverse events” to occur. Many people as younger people. As the would contract the virus, and existing vaccines, including the vaccines get distributed, the vac- more than 160,000 would die. flu shot, also can cause rare cine makers and the CDC will Measures that reduce the virus’s complications, including Guil- continue to monitor the effec- spread—like mask-wearing, lain-Barré syndrome, seizures tiveness of the vaccine in people social distancing and rapid- and sudden unexplained death. 65 and older who, because of result testing—can still have While this sounds frightening, age-related changes in their profound effects. Public health the risk is minuscule when con- immune systems, often don’t officials hope that people will sidered over the millions of respond as well to vaccination as continue to take these precau- people who are safely vaccinated younger people do. But just as tions at least until the country each year, and some of these certain flu vaccines have been reaches a vaccination rate of 70 complications can be triggered developed to evoke a stronger to 75 percent. k DISCLAIMER: Nothing shared on these pages should be construed or is intended to be used for medical diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified health care provider. Should you have any emergency questions or concerns, please contact your physician or health care provider immediately. Always consult with your physician or other health care provider to gain clarification regarding any health care related questions. This content was sourced from the CDC, the CMTA Scientific Advisory Board, the Muscular Dystrophy Association and the New York Times. WINTER 2021 THE CMTA REPORT 5
Filmmaker Crystal Emery: Energy in Motion and Spirit BY MARCIA SEMMES took the use of larly bad fall, her left hip slipped “Obstacles are those her arms and out of place, requiring major CMT legs from writer/producer/filmmaker surgery and landing her in a body cast for two months, an frightful things you see when you Crystal Emery, but it can’t touch experience she calls “nothing her indomitable spirit. “I refuse short of traumatizing.” take your eyes off to be defined by the body I She walked more slowly your goals.” inhabit,” she says, adding, “As a after being liberated from the deeply passionate and creative cast but continued to take dance renowned theater director Lloyd individual, I am so much more classes and play softball. Her Richards (“The Piano Lesson”). than a Black woman living with orthopedist said she needed She polished her craft under a life-altering physical disability. more physical therapy, and her director Bill Duke (“A Rage in I am energy in motion and physical therapist said she was Harlem”), then went on to earn spirit first.” “lazy.” Faced with the doctors’ a master’s in media studies from Crystal’s latest documentary, criticisms and lack of tangible The New School for Public “The Deadliest Disease,” is about guidance, she eventually stopped Engagement. the scourge of racism in health going to therapy altogether. Since then, Crystal has care, with COVID-19 as Exhibit Crystal began to experience a produced socially conscious A. She held a virtual screening slight drop foot in tenth grade storytelling that celebrates the narrated by Soledad O’Brien in and by the end of high school, triumph of the human spirit on a May 2020 and the film will be she couldn’t walk the 12 blocks variety of platforms. In addition broadcast on American Public from high school to her job to “The Deadliest Disease,” her Television in 2021. downtown. filmography includes “Black Crystal grew up in New In 1981, after years of slow Women in Medicine,” both of Haven, Connecticut, with a pas- decline, Crystal was diagnosed which she wrote, directed and sion for acting. She wrote and with a form of CMT that affects produced. The latter has been directed her first play in the fifth both her limbs and her respira- seen by 12 million people glob- grade. In the sixth grade, she tory system. Once again, it ally. Her writing has appeared in began falling without tripping. didn’t stop her—after earning numerous publications, includ- While she intuited that some- a BA from the University of ing Time magazine and The thing was seriously wrong, Connecticut, she began her pro- Huffington Post. Her published everyone else wrote it off as fessional career in theater and works include the first two vol- clumsiness. After one particu- film with an apprenticeship with umes of the Little Man children’s 6 THE CMTA REPORT WINTER 2021
book series; Against All Odds: Black Women in Medicine; and CMTA Board Approves Master Builders of the Modern World: Reimagining the Face Grants to Jackson Lab to of STEM (science, technology, engineering and math). Study Two Inhibitors Crystal is also the founder and CEO of URU The Right to he CMTA Board of Be, Inc., a non-profit content Directors approved two production company that fosters communication and understanding among diverse people by discovering and applying tangible multimedia solutions at the intersection of T research grants to Robert Burgess, PhD, at the Jack- son Laboratory in 2020. The first grant of $45,000 will be used to explore HDAC6 (histone deacetylase 6) the arts, humanities, science inhibitors, a potential therapeu- and technology. Crystal’s goal is tic approach for multiple forms to move all stakeholders toward of CMT. The many genes associ- a more equitable and humane ated with CMT make it unlikely world. She also conceived, that a single treatment will work designed and launched the for all forms of the disease, but innovative Changing the Face of preclinical studies with HDAC6 Dr. Robert Burgess, PhD STEM national educational ini- inhibitors, which have been With the second grant of tiative in 2015. The culmination shown to reduce motor and sen- $110,000, Dr. Burgess will study of this initiative was a 2017 sory deficits, have demonstrated whether inhibiting SARM1 is of congressional forum in Wash- promising results in several therapeutic benefit in multiple ington D.C., in conjunction with mouse models of CMT. Based on forms of CMT. SARM1 (sterile the National Academy of Sci- these promising results, scien- alpha and toll interleukin recep- ence, attended by more than tists believe that HDAC6 tor motif containing protein 1) 500 STEM professionals, poli- inhibitors might be beneficial in was identified in fruit flies as cymakers, educators, students treating a wide array of neurode- being actively involved in axon and members of the media. generative conditions including degeneration and similar effects Today, Crystal uses a demyelinating (Type were shown in SARM1 wheelchair and a ventilator, 1 and 4) and axonal Preclinical knockout mice. relying on friends and health (Type 2) CMTs. models of The hypothesis is aides to help her eat, bathe and Dr. Burgess, a that inhibition of get in and out of bed. It takes HDAC6… have member of the SARM1 may be bene- her 2.5 hours to get from bed to CMTA’s Scientific promising results ficial in some, but not demonstrated wheelchair in the morning. Advisory Board, will in several mouse all, forms of CMT. That’s a challenge, she says, but use mouse models of models of CMT. The results obtained the bigger challenges come in several forms of CMT in these five CMT the way CMT affects her ability to determine which types may be models (1A, 1X, 2E, 2D, 2S) will to hang out with friends, go to candidates for treatment with be definitive and publishable and her family’s homes and work as HDAC6 inhibitors and whether are not part of a larger effort on an artist. HDAC6 inhibitors may be of SARM1 in the Burgess lab. How- Nonetheless, she says, therapeutic benefit across a vari- ever, these results are important “CMT doesn’t dominate me. ety of CMT types. The latter will for the field and relevant to drug It’s just like any other obstacle. help inform whether patients development efforts that are You just have to figure out how with genetically undiagnosed already underway. Furthermore, to get around it.” Quoting cases of CMT are likely to bene- though this proposal is a pilot of Henry Ford, she added, “Obsta- fit from this therapeutic modest scale, the results will cles are those frightful things strategy, or whether only select inform future research on just you see when you take your forms of CMT may respond to how generally applicable SARM1 eyes off your goals.” k this treatment. inhibitors may be in CMT. k WINTER 2021 THE CMTA REPORT 7
Two New Members Join Advisory Board The CMTA welcomed two new members to its Advisory Board in 2020, part of its mission to provide enhanced expertise in a wide variety of fields to the community. CHRISTINE MURRAY, MD, is a board-certified reproductive endocrinologist and infertility (REI) specialist. She specializes in in vitro fertilization and polycystic ovary syndrome with a special interest in preimplantation genetic testing of embryos, a technology that helps families deal with genetically inherited disorders and offers an approach to building families with an increased knowledge of, and options to address, genetically inherited syndromes. She has spent 20 years in Vermont as an academic physician involved with the training of medical students, residents and fellows. After medical school at the Mayo Graduate School of Medicine, she underwent OB/GYN residency training at McGill University in Montreal, Christine Murray, MD Quebec, followed by a fellowship in reproductive endocrinology and infertility. From 1999-2014, Dr. Murray worked at the University of Vermont Medical Center and was an associate professor in the Division of Reproductive Endocrinology. In addition to a busy clinical practice, Dr. Murray became residency program director in 2004 and held that position for eight years. In 2015, Dr. Murray opened Northeastern Reproductive Medicine to bring affordable, comfortable fertility care to patients wishing to build their families. Dr. Murray became interested in the CMT community through her close friendship with the Ouellette family, who started the Vermont Cycle (and Walk) for CMT. She is interested in helping families understand their reproductive options and hopes that her extensive connections within the reproductive medicine community can provide answers and assistance. TERESA CARROLL, MS, PHD, is an organismal biologist with more than 25 years of experience in higher education, primarily as an associate professor of biology in Missouri. In 2016, she moved to South Carolina, where she continued teaching at a small regional university and is currently writing topic-specific manuals for use in undergraduate biological labs. Diagnosed with CMT1X in 1994, Teresa is an advocate and long-time supporter of the CMTA and has spent many hours since her diagnosis studying the scientific literature on CMT1X in an effort to understand her condition. Given that her career included taking com- plex biological information and making it comprehensible for Teresa Carroll, MS, PhD undergraduate biology majors, Teresa is excited to have the opportu- nity to use those skills to build patient-friendly communications that help her fellow CMT patients and their families better understand the disease. k 8 THE CMTA REPORT WINTER 2021
Walks 4 CMT Raised Nearly $180,000 volunteers hosted 26 CMTA THE CMTA THANKS virtual all the leaders and participants for their walks in 2020, raising nearly flexibility and creativity $180,000 despite the in raising research funds during this disruptions and restrictions difficult time. The caused by the pandemic. leaders are: Because the 2020 Walks 4 CALIFORNIA CMT were virtual, participants Los Angeles: were not limited by time or loca- Alani Price and John Ramos Palo Alto: tion. Teams held smaller walks Ori Bash and Tau O’Sullivan with their families and walk San Diego: Kendall Trout COLORADO leaders held virtual events using Denver: Carol Ris Zoom and social media. Many DISTRICT OF COLUMBIA kicked things off with a fun Washington: Steve Weiss FLORIDA activity like a Bingo or trivia for our walk in the local newspa- and led solely by volunteers. Any Miami: U of Miami CMT Clinic game night, then walked for an per, and I was featured on a local city or town can host a Walk 4 Parkland: Lara Rustici Tampa: Sarah Gentry entire month, some in smaller program on our ABC affiliate in CMT—all it takes is one leader to GEORGIA groups, all with proper social Syracuse.” step forward. The CMTA makes Atlanta: Jeannie Zibrida distancing. Mike went on, “We should it simple to host a walk with a ILLINOIS The Syracuse, NY Branch have a good time and gather, Walk4CMT.org website, turnkey Chicago: Doreen Pomykala MAINE kicked off its walk with a face even during these rough times templates for sponsorship and Peaks Island: Mary Louie mask fashion show on Zoom and with the pandemic. I feel that a marketing and support from our MARYLAND went on to beat both last year’s positive outlook helps with dedicated staff. k Baltimore: Clark Semmes MASSACHUSETTS record and their goal for this meetings and other activities. Boston: Jill Ricci year. According to Branch We were very fortunate this year NEW YORK Leader Mike Casey, “After a cou- to have the Bucks County, PA If you want to be part of Long Island: Jessica Aviles Syracuse: Mike Casey ple of weeks, I decided that if we and Albany, NY Branches join this amazing success, OHIO were going to make a Virtual us. I can't wait until next year look for a 2021 walk at Cincinnati: Jill Stuhlmueller Walk successful, we had to keep when we can have a walk in www.Walk4CMT.org. Cleveland: Shelly McMahon Columbus: Jessica Diamond a positive outlook. So, I used my person.” Or if you’re ready to host OKLAHOMA email and was on Facebook on a The CMTA is one of the few a Walk 4 CMT in your Lonna Henry very regular basis asking for national non-profit organizations community, contact PENNSYLVANIA Pittsburgh: Debbie Czarnecki donations. I got more exposure with a walk campaign organized CMTA Events Manager Julie Chester County: Ashley Trout Tarle at julie@cmtausa.org. TENNESSEE Nashville: Teresa Shoaf TEXAS Dallas/Ft. Worth: Thomas Roderiguz 2020 WALK 4 CMT WASHINGTON Seattle: Emily Osborne HIGHLIGHTS ONTARIO, CANADA Fergus: Kelly Hall 26 Walk 4 CMT Events 459 Participants 11 Sites Raised Over $5k 5 Sites Raised Over $10k DC Walk Raised a Record-Breaking $42,000 Top Team “The Mighty Quinn” in Washington, DC Raised $22,810 Parkland (FL) Walk 4 CMT $180,000 Raised for CMT Research WINTER 2021 THE CMTA REPORT 9
Advances in Genetics: New Tools for Prospective Families BY CHRISTINE MURRAY, MD dvances in genetic tech- disorder. Huntington’s disease are more common among certain nology have allowed for and Marfan syndrome are exam- populations. Comprehensive car- A the development of powerful tools to assist people as they begin to plan their families. Multiple techniques are available to pro- vide prospective parents with ples of autosomal dominant inheritance. X and Y chromo- somes can also carry genetic mutations: Hemophilia and frag- ile X syndrome have an X-linked inheritance pattern. rier screening panels now test for nearly 300 single-gene defects. The American College of Obstetrics and Gynecology rec- ommends that women have genetic carrier screening as part valuable information to plan and The Human Genome Project, of their routine prenatal evalua- prepare. This overview, while not a multinational scientific collab- tion. Reproductive options for comprehensive, offers a look into oration completed in 2003, is at-risk couples include IVF with what modern genetic analysis widely considered one of the preimplantation genetic testing can do. most ambitious scientific under- (PGT), conception with donor A review of basic genetics takings of all time. The finished eggs or sperm or adoption. provides a good starting point. project sequenced 3 billion DNA Human beings have cells con- letters covering 99 percent of the taining 46 chromosomes: Two human gene-containing regions. NON-INVASIVE PRENATAL will code for gender at birth (X It is hard to overstate the NiPT is a genetic test that is per- TESTING/SCREENING and Y). The remaining 22 auto- tremendous impact of this under- formed once pregnancy has been some pairs consist of maternal taking. The results have been established. It requires a simple and paternal DNA. These paired used to identify a genetic source blood draw and can be done as chromosomes contain hundreds for a multitude of medical issues, early as nine to 10 weeks of preg- of thousands of DNA strands— including cancers, as arising from nancy. The test analyzes tiny genes that code for all the traits specific mutations. Understand- fragments of cell-free DNA from that make us who we are. ing the genetic basis of disease the developing placenta to assess Defects in any of these genes can opens the door for specific diag- the genetic health of the devel- lead to specific disorders. Such nostic tools and treatments. oping baby. single-gene mutations can be Unlike carrier screening, inherited in an autosomal reces- which provides information sive manner, which means that about specific genes, NiPT is GENETIC CARRIER an affected child received one Carrier screening refers to a used to detect chromosomal dis- SCREENING defective gene from each parent. blood test that can identify silent orders that are caused by the The parents, each having gene mutations. Prospective par- presence of an extra or missing only one affected gene, are con- ents are now routinely offered copy (aneuploidy) of a chromo- sidered silent carriers and are this screening to identify some of some. NiPT primarily looks for not affected by the disorder. the most common mutations like trisomy 21 (Down syndrome), Their offspring has a 25 percent the genes for cystic fibrosis (CF), caused by an extra chromosome chance of having the disorder spinal muscular atrophy and at position 21, trisomy 13 and 18 and a 50 percent chance of being fragile X syndrome. This basic and extra or missing copies of a silent carrier. carrier panel is offered to one the X and Y chromosome. NiPT Examples of autosomal potential parent. If a silent can also identify gender. NiPT is recessive disorders are cystic mutation is identified, the other a screening test, which means fibrosis, sickle cell anemia and parent is tested. There are that it cannot give a definitive spinal muscular atrophy. Some expanded panels recommended answer about whether the preg- disorders are autosomal domi- for parents based on their ethnic nancy is affected. The test can nant—inheriting only one backgrounds. Tay Sachs, sickle only estimate whether the risk of abnormal gene will lead to the cell anemia and the thalassemias having certain conditions is 10 THE CMTA REPORT WINTER 2021
increased. An abnormal result is then performing a biopsy of the detect the presence of the spe- usually followed by more defini- embryo to remove a small num- cific mutation gene: Two copies tive testing (amniocentesis or ber of cells that can then be indicate an affected embryo; one chorionic villous sampling). tested. Typically, an embryo is copy would identify embryos grown (incubated) in a labora- destined to become genetic carri- tory for five days after ers of CF and those without fertilization. A 5-day-old embryo probe activity would be consid- PREIMPLANTATION Since 1974, IVF has been used (blastocyst) has an inner cell ered unaffected. GENETIC TESTING to help millions of couples who mass—which is destined to To illustrate, a prospective were unable to conceive for a become the baby—and an outer mother is tested for cystic fibro- variety of reasons: blocked cell mass (trophectoderm) that sis and found to be a silent Fallopian tubes, issues with will ultimately develop into the carrier of a CF mutation. Her ovulation or sperm production placenta and amnion. Using an partner is then tested and is also and endometriosis, to name a incredibly small and precise a carrier of a CF mutation. There few. It is estimated that over laser, a small opening is made in is a 25 percent chance of having 8 million babies have been con- the wall of the embryo and cells a baby with cystic fibrosis, which ceived via IVF since Louise are removed from the trophecto- affects multiple organs—particu- Brown—the first IVF success— derm. The embryo is then frozen larly the lungs. Incredible was born in 1974. while the cells are tested. advances in treatments have The advent of preimplanta- PGT-A tests the cells for an been made and, armed with this tion genetic testing (PGT) has abnormal number or pairing of knowledge, the couple may elect added another group of prospec- chromosomes (aneuploidy). to proceed with conceiving on tive parents: those who have Selecting embryos with a normal their own. They could also family or personal histories of number and arrangement of decide to conceive using an egg genetically inherited conditions chromosomes (euploid) to trans- or sperm from a donor who does or who are at a higher risk of fer back to the patient not carry the CF mutation. They chromosomal anomalies due to significantly increases the might choose to adopt. They can advanced maternal age or recur- chances of a healthy pregnancy. also elect to have IVF and test rent unexplained pregnancy PGT-M refers to testing the their embryos for cystic fibrosis. losses. embryos for single-gene muta- PGT-M is now widely PGT refers to the process of tions like the one that causes CF. utilized to identify embryos creating embryos via IVF and A probe is created that can (continued on page 13) WINTER 2021 THE CMTA REPORT 11
Youth Council Member Emmily Stufflet (front row, center) held a fundraiser and awareness event for CMT at her high school in Florida in 2020. Youth Council Gearing Up for Big Fundraising Year embers of the CMTA’s “Walk a Mile in Our Braces,” a Maya Grochowska, “Attending Youth Council raised book charting the experiences of Camp Footprint and meeting so M in 2021. more than $7,000 for the CMTA in 2020 and look forward to keeping the momentum going “This is the year we get the 75 youth with CMT and the first- ever Global Online Dance-a-thon 4 CMT. The council has also devel- oped a “Fundraising E-Kit,” a presentation filled with informa- many other kids with CMT inspired me to be more open about my CMT. And it made me want to raise money for the CMTA. Meeting other kids with CMT drove home that I’m not whole community of youth tion on the different ways to alone and all of us with CMT involved because together there fundraise and get involved. The deserve hope for a cure.” is no stopping us,” the Youth E-kits are downloadable and tai- Hannah Roberts said she Council’s Fundraising Commit- lored specifically for situations is “inspired to raise money for tee—Elijah Tolz, Paola Martinez like school fundraisers, Walks 4 the CMTA because of its com- and Evan Zeltsar—said in a CMT and birthday celebrations. mitment to research and passion statement. They are available on the CMTA for community. I’m inspired The three are spread out on website. because of my tribe and the opposite coasts but share a pas- Two young fundraisers impact for future generations sion for fundraising to cure CMT shared their motivation for help- living with Charcot-Marie- and are “determined and ready ing the CMTA. According to Tooth disease.” k to encourage other youth in the community to make a difference.” Plans for 2021 include a vir- FOR MORE INFORMATION on getting involved with the tual bingo game, publication of CMTA’s Youth Program, go to www.cmtausa.org/youthprogram. 12 THE CMTA REPORT WINTER 2021
peripheral nerve axon or the novo mutations would not be myelin sheath. More than 100 identified by traditional PGT-M GENETIC TESTING genes have been identified in techniques. (continued from page 11) affected by a great number of CMT, with each gene linked to Advances in genetic and genetically inherited disorders one or more types of the disease. reproductive technologies can that demonstrate a specific In addition, multiple genes can expand reproductive options for pattern of inheritance. Some be linked to one type of CMT. many who, until recently, had disorders, however, are consid- Moreover, the inheritance pat- very few. They can provide ered multifactorial. There may tern can be autosomal dominant, knowledge to aid in planning be a genetic component, but X-linked or autosomal recessive. and preparedness for pregnan- other factors are required to It can also appear as a de novo cies affected by heritable medical develop a specific disease. For mutation. disorders or chromosomal example, some women may have While these variations pre- abnormalities and ultimately a BRCA mutation. While this sent a challenge to probe expand our approach to the diag- confers a significantly increased development for PGT-M, it is nosis and treatment of complex risk of breast and ovarian can- still an option for many. Perhaps diseases. cer, not everyone who carries as many as 50-60 percent of For more information, a the mutation will develop the cases involve the duplication of helpful start can be found at disease. Some genetic disorders the PMP22 gene on chromosome ReproductiveFacts.org. k carry a highly variable inheri- 17. Traditional PGT-M can be Christine Murray, the newest member tance pattern. considered in such cases. Some of the CMTA Advisory Board, is a CMT is in this category. cases can involve the deletion of board-certified reproductive endocri- CMT is caused by mutations in this gene or some other variant; nologist and infertility (REI) specialist. She specializes in in vitro fertilization genes that support or produce these cases typically require and polycystic ovary syndrome with a proteins involved in the struc- phasing-clinical testing of the special interest in preimplantation ture and function of either the patient’s parents. Presently, de genetic testing of embryos. WINTER 2021 THE CMTA REPORT 13
INNERVATORS WHY I GIVE: For anyone thinking of donating to the CMTA or its STAR research program, ACCORDING TO THE DICTIONARY, an innervator is a nerve stimulator. According to the Howard Landis has four simple words CMTA, an INNERVATOR is an action-oriented donor of advice: “Now is the time.” who gives monthly to the organization, sustaining STAR (Strategy to Accelerate Research), our premier research initiative, as well as important community initiatives like Camp Footprint, Patient/Family Conferences and educational programs. All of these Howard has a late-onset their genome sequenced may programs require steady, reliable support from form of CMT 2 for which the cul- have hundreds of disease-caus- prit gene has not yet been ing mutations, Howard committed donors. Please join the Innervators today! identified, but the fact that the explained. Most of these variants www.cmtausa.org/cmta-innervators exact cause hasn’t yet been are harmless—everyone has pinned down doesn’t stop him thousands of mutations—and Tracy Adamson Mr. and Mrs. Ryan Meloni from getting involved and giving. determining which one is not is Scott Allen Ronnie Mendoza As he noted, “The research com- the challenge. The challenge is Brendan Bennett Mr. and Mrs. Jacob Mersing Lorna Brand William Millar munity is doing its part and is much easier if there is a second Dr. and Mrs. William Buchanan Mrs. Susan Moore making tremendous advances. and a third patient, who might Cynthia Carroll Ms. Alba Moratinos Now is the time to join the be halfway across the world, with William Chandler Ms. Cara Natale Peter Cherpes David Nelson CMTA in supporting them with the same mutation. “It is a gross David Coldiron Gary Oelze your contributions, and now is oversimplification to say that Peter Cole Mr. and Mrs. Pamela Palmer the time to have your genome identifying culprits is a numbers James Copeland Jeannie Palmero John Cordonnier Jonathan Preston sequenced if you have an game, but there is a sense in Diane Covington Susan Rems unidentified form of CMT. Your which this is true,” Howard Grace Dipisa Raymond Roth funds and your genomes will explained. He noted that the Ms. Marilynn Dodge Mrs. Margery Sayward undoubtedly make a difference.” Genesis Project faces a number Mitchell Fedde Mr. and Mrs. Mario Scacco Mr. and Mrs. Rick Fansler Donald Schlosser Howard is particularly inter- of barriers—i.e., many people Mrs. Arya Fritz Bruce Spackman ested in the work that Dr. with unidentified forms of CMT Tim Garmager Joyce Steinkamp Stephan Züchner is doing on do not know that they have the Mr. and Mrs. Stephen Giles Mr. and Mrs. Jim Stetor Amy Gray Mrs. Barbara Stuck unidentified Type 2s at the Gen- disease and many who have been Mr. and Mrs. Jay Grife Brett Taylor esis Project at the University of diagnosed have not had their Diane Gross Mrs. Patricia Tedford Miami. Genesis, a cloud-based genome or exome sequenced. In Randy Gunn David Thomas Mr. and Mrs. William Helmke Mr. and Mrs. Ophir Trigalo database designed for storing addition, some researchers and Diann Jackson Payton Turner and analyzing genomic data, companies don’t wish to share Mark Johnsen Lynn Upton recently identified a new form of their data. Doug Kampe Angela Vandersteen CMT affecting an estimated Breaking down these barri- Heather Kercher Bruce Vieira Drs. Craig and Andrea Kesack Steve Williard 3,000 people in the United ers is more important than ever Ella Lafara Robert Wills States. Howard is on the board given the progress being made Jennifer Larkin Daniel Woltjer of Genesis, which is available to with gene therapy and other Rosemarie Littleton the worldwide research commu- treatments, Howard said, noting nity, making the challenge of that the Genesis researchers who “I am an Innervator because I know the identifying culprit genes easier. recently located a new gene also budgetary challenges nonprofits face in With more genomes and exomes identified an existing medication terms of planning. So often the bulk of from CMT patients available to that will treat and possibly cure giving occurs late in the fourth quarter. researchers, the research com- the disease. “That sort of thing If enough people provide monthly giving over the course of the year, it will provide the CMTA with the stable funding it munity could identify many just wasn’t possible even five more forms of CMT. years ago,” he added. needs to fulfill its mission of ridding the Individuals with an uniden- Howard’s own CMT journey world of this affliction.” —David Coldiron tified form of CMT who have was different than most. He had 14 THE CMTA REPORT WINTER 2021
HOWARD LANDIS no significant symptoms when his genome has been sequenced he was diagnosed 12 years ago at and if Howard’s culprit gene is the age of 54. He grew up on a identified researchers will be small farm in Pennsylvania and able to determine if he had the wasn’t aware of any CMT symp- disease too. Howard has one sib- toms in his earlier years ling and one child and so far although he has a high instep neither shows signs of CMT. and was prone to ankle sprains. Howard initially viewed the He went on to work in Manhat- CMTA as a resource for learning tan as an accountant and more about the disease, then consultant for a couple of years later began attending and then spent most Patient/Family Con- of his career with a Now is the ferences and online small private equity webinars. He says firm in Connecticut. that his experiences time to join He was referred to a have been uniformly the CMTA in neurologist by an positive and that he supporting the Howard Landis orthopedist treating research “continues to be organization that is well run, he him for a shoulder community… amazed at the caliber added, noting that the CMTA has a injury. The orthope- and dedication of the 4-star rating from Charity Naviga- dist noticed some wasting in the people that are working to sup- tor—and a clearly defined mission area between his thumb and port CMT patients and the that has a reasonable chance of index finger and thought it research community that is succeeding. might be CMT. A nerve conduc- working hard to find treatments Currently retired and living tion test confirmed his hunch. and cures for CMT.” in South Florida, Howard closely Howard thinks his father, Howard says the CMTA fits follows CMT research and lives who passed away several years into his philosophy of giving, which out his own philosophy of giv- ago, probably had CMT. He was is whether it makes a difference. ing—making a difference in the never seen by a neurologist, but Ideally, that means giving to an lives of everyone with CMT. k ! BECOME AN INNERVATOR! Support the CMTA’s Life-changing Initiatives with a Monthly Gift Complete and return to: CMTA • PO Box 105 • Glenolden, PA 19036 l $15 monthly l $25 monthly l $50 monthly l $100 monthly l $500 monthly l Other: $_______________________ Charge my l Visa l MasterCard l American Express Donate online at www.cmtausa.org/donate Name______________________________________________________________ Card #________________________________________________Exp. Date__________ Signature________________________________________ Address_____________________________________________________________________________________ City______________________________________________ State_________ Zip_______________________ Phone_____________________________________________ Please send me CMTA updates via email at: ______________________________________________________________________________________________________ To give a gift of stock or learn about leaving a legacy gift to the CMTA, please call or email Jeana Sweeney, 800-606-2682 x106 / jeana@cmtausa.org.
Three New CMTA Centers of Excellence The CMTA designated three new Centers of Excellence in 2020, bringing the international total to 40. Adding to the CMTA’s wide network of clinical support ensures that as many people as possible have access to expert advice and care. Like all of the centers, they are led by professionals with deep experience in treating CMT. N E W J E R S E Y DR. FLORIAN THOMAS, at the Hackensack University Medical Center in New Jersey, has cared for people with CMT and engaged in CMT research for over 30 years. He has long been active with CMT advocacy groups, and in 1998 co-founded the CMTA peer support group in St. Louis, Missouri. He is fellowship-trained in neuromuscular research and board-certified in neurology and neural repair and rehabilitation. He is the chair of the Neuro- science Institute and the Department of Neurology at Hackensack Meridian School of Medicine. He has published on several CMT subtypes, identified, with an international team of collaborators, a novel CMT disease gene and spearheaded two of the first clinical drug trials for CMT in the United States. Additional treatment studies are being initiated. For appointments, call 551-996-1324 or email Annerys.Santos@HMHN.org. C O L O R A D O DR. MICHELE YANG is a pediatric neurologist at Children’s Hospital Colorado with certification in neuromuscular disorders and electrophysiology. She trained at the Children’s Hospital of Pittsburgh in pediatrics and child neurology, at Beth Israel Deaconess Medical Center in electromyography and at Children’s Hospital of Philadelphia in pediatric neuromuscular medicine. For appointments, call 720-777-3907 or email Allison.ballard@childrenscolorado.org. C A L I F O R N I A DR. ALEXANDER FAY, at the University of California San Francisco (UCSF), is a pediatric neurologist with a focus on neuromuscular disorders. He obtained his PhD in biophysics and his MD from UCSF and completed his child neurology residency and neuromuscular fellowship at Washington University in St. Louis. Since joining the faculty at UCSF, he has devoted his time to identifying a novel form of CMT in a large family from South America, developing CRISPR-based therapeutics for CMT2, serving as an investigator on several clinical trials for childhood neuromuscular diseases and expanding his neuromuscular practice to include UCSF Benioff Children’s Hospitals in both San Francisco and Oakland. He is a native of the Bay Area and is proud to be serving this community. For appointments, call 415-353-7596 or email Audrey.glancy@ucsf.edu. 16 THE CMTA REPORT WINTER 2021
Named In 2020 CMTA CENTER OF EXCELLENCE CLINICAL DIRECTOR Cedars-Sinai Medical Center (Los Angeles)..................................................................................Drs. Matthew Burford and Richard Lewis Children's Hospital Colorado (Aurora)* ..............................................................................................................................Dr. Michele Yang Children’s Hospital of Philadelphia (Philadelphia) ...............................................................................................................Dr. Sabrina Yum Children’s Hospital of Pittsburgh (Pittsburgh)*.........................................................................................................Dr. Hodas Abdel-Hamid Children’s National Hospital (Washington, DC)* .................................................................................................Dr. Diana Bharucha-Goebel Connecticut Children’s Medical Center (Farmington) ..........................................................................................................Dr. Gyula Acsadi Hackensack University Medical Center (Hackensack, NJ)* .............................................................................................Dr. Florian Thomas Hospital for Special Care* (New Britain, CT) ....................................................................................................................Dr. Kevin J. Felice Johns Hopkins University (Baltimore) ...............................................................................................................................Dr. Thomas Lloyd Kane Hall Barry Neurology (Dallas/Fort Worth)* .............................................................................................................Dr. Sharique Ansari Lucile Packard Children’s Hospital at Stanford (Palo Alto) ......................................................................Drs. John Day and Ana Tesi Rocha Massachusetts General Hospital (Boston) .................................................................................................................Dr. Reza Seyedsadjadi Nationwide Children's Hospital (Columbus)* ....................................................................................................................Dr. Zarife Sahenk Nemours Children’s Hospital (Orlando) ............................................................................................................................Dr. Richard Finkel Northwestern Memorial Hospital (Chicago)* ...................................................................................................Dr. Daniela Maria Menichella Ohio State University (Columbus).............................................................................................................................Dr. Samantha LoRusso Oregon Health & Science University (Portland)* ................................................................................................................Dr. Chafic Karam Rush University (Chicago)* ........................................................................................................................................Dr. Ryan D. Jacobson Stanford Neuroscience Health Center (Palo Alto) ....................................................................................................................Dr. John Day University of California (San Francisco)* ...................................................................................................................................Dr. Alex Fay University of Colorado (Aurora)* ........................................................................................................................................Dr. Vera Fridman University of Florida (Gainesville)* ...................................................................................................................................Dr. James Wymer University of Illinois at Chicago (Chicago)* ................................................................................................................Dr. Charles K. Abrams University of Iowa (Iowa City) ............................................................................................................................................Dr. Michael Shy University of Miami (Miami) .............................................................................................................................................Dr. Mario Saporta University of Michigan (Ann Arbor)*..............................................................................................................................Dr. Dustin Nowacek University of Minnesota (Maple Grove) ................................................................................................................................Dr. David Walk University of Missouri (Columbia)..........................................................................................................................Dr. Raghav Govindarajan University of North Carolina (Chapel Hill)* .......................................................................................................................Dr. Rebecca Traub University of Pennsylvania (Philadelphia) ......................................................................................................................Dr. Steven Scherer University of Pittsburgh Medical Center (Pittsburgh)*......................................................................................................Dr. Sasha Zivkovic University of Rochester (Rochester, NY) .......................................................................................................................Dr. David Herrmann University of Texas Southwestern (Dallas)* ..................................................................................Drs. Susan Iannaccone and Diana Castro University of Utah (Salt Lake City) .............................................................................................................................Dr. Russell Butterfield University of Washington (Seattle) ...................................................................................................................................Dr. Michael Weiss Washington University SOM St. Louis (St. Louis)* ...........................................................................................................Dr.Stefanie Geisler Wayne State University (Detroit)...................................................................................................................................................Dr. Jun Li *These Centers of Excellence are not part of the INC. INTERNATIONAL The Children’s Hospital (Westmead, Australia)...............................................................................................................Dr. Manoj Menezes The National Hospital for Neurology & Neurosurgery (London, England) ...............................................................................Dr. Mary Reilly C. Besta Neurological Institute (Milan, Italy) .................................................................................................................Dr. Davide Pareyson University of Antwerp (Edegem, Belgium) ......................................................................................................................Dr. Jonathan Baets CMTA CENTERS OF EXCELLENCE are patient-centric, multidisciplinary CMT clinics where children, adults and families affected by CMT can be assured of receiving comprehensive care by a team of CMT experts. The Centers roughly correspond to the 21 international sites that make up the NIH Inherited Neuropathies Consortium (INC)—a group of academic medical centers, patient support organizations and clinical research resources sponsored in part by the CMTA. The centers will become even more important as the CMTA begins clinical trials, which will depend on how much we know about the “natural history” of CMT—how different types of CMT progress over time and whether novel medications are slowing the course of the disease. Much of that information will be supplied by the Centers of Excellence. CMTA CENTERS OF EXCELLENCE www.cmtausa.org/coe WINTER 2021 THE CMTA REPORT 17
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