Help forToday, Hope for Tomorrow

Charcot-Marie-Tooth Association

Now, more than ever, the Charcot-Marie-Tooth Association is providing the CMT community hope for tomorrow. The pace of its Strategy to Accelerate Research (STAR) quickened in 2015 as its global team of renowned scientists pushed forward with a structured, collaborative drug development program that includes the latest scientific and technological advances. CMTA partners in the pharmaceutical and biotechnology industries, along with the National Institutes of Health, have completed initial screening of millions of compounds at labs nationwide and secondary screening is ongoing.

Launched in 2008, STAR has produced complex laboratory models of CMT, utilizing rapid drug discovery technologies to identify drugs that modify the genetic causes of CMT. STAR is uniquely positioned to deliver medicinal candidates to the market in the near future.

While the CMTA is pushing hard on drug discovery, it also offers community members help for today. The CMTA branches provide members education, support and services while Patient/Family Conferences offer a chance for members to get firsthand information from the clinicians and researchers who are fighting to cure their disease. Numerous publications are available, including the long-running CMTA Report and the newly launched CMTeen, an online magazine by, for and about teenagers with CMT. A newly revamped website, a web app that puts the website in users’ back pockets and Facebook groups that allow members to connect based on their interests complete the member services picture.

Until now, treatment for those with Charcot-Marie-Tooth has been limited to therapeutic interventions, including bracing, physical therapy and surgery. Thanks to STAR, the hope for a drug treatment is poised to become a reality.

Help for Today, Hope for Tomorrow

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Charcot-Marie-Tooth (CMT) is the most commonly inherited peripheral neuropathy, estimated to affect one in every 2,500 people, more than 2.8 million people worldwide, without regard to age, gender or ethnicity. Identified in 1886 by three physicians—Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth—CMT is a progressive disorder that slowly damages the nerve cells leading to a person’s extremities. There is no way to predict how far or how fast the disease will progress, and the severity varies widely from person to person. Some are able to go about their lives with only moderate difficulty, while others require greater assistance. In rare cases, CMT can be fatal.

Signs and Symptoms of CMT Early signs include frequent tripping or clumsiness, often accompanied by an abnormal burning sensa-tion in the feet or hands. As the disorder progresses, symptoms may include:

• Weakness and loss of function in feet/legs or hands/arms

• Neuropathic pain

• Foot drop, poor balance and gait abnormalities

• Sensory loss or abnormal sensation

• Structural changes, such as high arches, hammertoes, claw fingers or toes, scoliosis, kyphosis or muscle loss

The staff and board of the CMTA all have CMT or loved ones with CMT. Quite literally, we feel your pain. That’s why we’re working as hard as we can to find treatments for CMT—to halt it in its tracks before it hobbles our chil-dren or disables our grandchildren. There’s even research suggesting that nerves can be re-myelinated and that those of us who currently suffer from the disease may see some relief in our lifetimes. While we work hard for the future, we’re also delivering the highest quality programs and services today. Before flipping ahead to learn more about STAR and how you can invest in a world without CMT, please take a moment to get to know us and find out what we’re doing to make a difference in people’s lives. —Patrick A. Livney, CEOOverview Founded in 1983, the CMTA is the leading source of in-formation about CMT for more than 30,000 patients and families, supportive friends and medical professionals. The CMTA offers a variety of educational materials and confer-ences, coordinates more than 70 local CMTA branches nationwide, provides physician referrals and works close-ly with the clinical and research communities. The CMTA is also the leading financial sponsor of research within the CMT community, and it is the only CMT-specific patient advocacy organization in the United States strategically aligned with the National Institutes of Health Rare Disease Clinical Research Network (RDCRN).

Independent Rating and Review In 2015, the CMTA earned Charity Navigator’s four-star rat-ing for the second year in a row. Only 21 percent of the nonprofits rated by Charity Navigator get two consecutive 4-star evaluations, indicating that the CMTA adheres to good governance and other best practices that minimize the chance of unethical activities and consistently executes its mission in a fiscally responsible way. The CMTA has also consistently been awarded the Independent Charities Seal of Excellence by the Independent Charities of America, an award given to organizations that annually meet the highest standards of public accountability, program performance and cost-effectiveness.

What is CMT ?Inheritance Factors Each child of a person affected with the dominant form of CMT has a 50-50 chance of inheriting the disease. People who carry the recessive CMT gene may also pass the disease on to their children. And, CMT may appear spontaneously in any family as a new mutation and then be passed on to future generations. Family history does not always indicate a risk of CMT.

There Is No Known Cure for CMT Although there is no known cure for CMT, common treatments include moderate exercise, physical and occupational therapy, bracing with custom-fitted orthoses and surgical intervention.

Diagnosis In addition to family history and clinical features, elec-tromyographic studies that measure the speed and strength of nerve conduction in the extremities are often performed to confirm a diagnosis of CMT. Genetic testing can also be done in order to identify a specific subtype of CMT. Once a subtype is identified in a family, other family members may have nerve conduction or genetic testing to determine if they are also affected.

Meet the Charcot-Marie-Tooth

Association

Patrick Livney Chief Executive Officer

Marcia Semmes Director of Print Communications

Kim Magee Director of Finance

Jeana Sweeney Director of Community Services

Susan Ruediger Director of Development

Bethany Meloche Director of Social Media

Ori Bash West Coast Regional Branch Manager

Michelle Hayes Midwest Regional Branch Manager

The mission of the CMTA is to support the development of drugs to treat CMT, to improve the quality of life for those with CMT, to increase awareness about CMT,

and, ultimately, to find a cure. Our vision is a world without CMT.

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John Svaren, PhD, Chair University of WisconsinFrank Baas MD, PhD University of Amsterdam NetherlandsRobert H. Baloh, MD, PhD Cedars-Sinai Medical Center Los AngelesM. Laura Feltri, MDUniversity at BuffaloJun Li, MD, PhD Vanderbilt University, NashvilleRudolph Martini, PhD University of Würzburg, GermanyKlaus-Armin Nave, PhD Max Planck Institute for Experimental Medicine, University of Göttingen, Germany

Brian Popko, MD University of ChicagoMario Saporta, MD, PhD University of MiamiSteven S. Scherer, MD, PhD University of PennsylvaniaMichael E. Shy, MD University of IowaGabsang Lee, PhD Johns Hopkins University BaltimoreLawrence Wrabetz, MD University at BuffaloStephan Züchner, MD, PhD University of Miami

The Therapy Expert Board is responsible for ensuring that each research project has translational value for the CMTA’s STAR mission of developing therapeutics for CMT patients. The members are:Mark Scheideler, PhD, Chair HumanFirst Therapeutics LLCLars J. Knutsen, PhD Discovery Pharma Consulting LLCClaes Wahlestedt, MD, PhD University of MiamiTage Honore, PhD Aestus Therapeutics Inc.

In recognition of the importance of translating scientific research into a treatment for CMT, the CMTA revamped its Scientific Advisory Board in 2015, bifurcating it into two function-driven entities. The newly formed STAR Advisory Board comprises a Scientific Expert Board (SEB) and a Therapy Expert Board (TEB).

The Scientific Expert Board provides scientific input for projects that are ongoing or proposed. The members are:

�e STAR Advisory Board

The CMTA is governed by a voluntary Board of Directors who bring both professional competence and personal commitment to their task. These business owners,

executives, doctors and lawyers oversee the organization’s operations and strategy for promoting awareness, funding research and finding a cure. Because they are all affected by CMT,

they are deeply committed to the organization and annually make significant financial contributions to ensure that it meets its goals.

�e CMTA Advisory BoardMembers of the CMTA Advisory Board bring both expertise and empathy to their positions,

assisting people with CMT in dealing with some of the critical issues facing them, from finding the most suitable orthotics to the best balance exercises to tips on how to talk about CMT.

They also write articles for The CMTA Report, participate in monthly webinars and assist CMTA members who have questions in areas in which they would be considered “experts.”

Gilles Bouchard (Chairman) Chairman and CEO, Livescribe Los Altos, CAGary Gasper (Treasurer) Partner, Ernst & Young Co-leader of the Washington Council Ernst & Young, Washington, D.C.Steve Weiss (Secretary) Senior Vice President - Health Edelman, Washington, DCHerb Beron Executive Director , Financial Advisor Morgan Stanley Wealth Management Florham Park, NJ Stephen Blevit, Esq. Partner, Sidley Austin, LLP Los Angeles, CALaura Fava Owner/Lawyer, Laura Fava Barrister & Solicitor, Toronto, Ontario

Alan Korowitz Executive Vice President of Sales Premiere Networks, a division of Clear Channel Media + Entertainment New York, NYSteve O’Donnell President, Steven F. O’Donnell Inc. Elkridge, MD Chris Ouellette Vice President of Operations and Service, Alpha Analytical Shelburne, VTElizabeth Ouellette Civic Volunteer and Community Relations Expert, Los Altos, CAPhyllis Sanders, Esq. Partner, The Sanders Law Firm Mineola, NY Steven Scherer, MD, PhD Professor of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia, PA

Michael Shy, MD Professor of Neurology Co-Director of Neuromuscular Program, Co-Director of MDA Clinic Director of the CMT Clinic Carver College of Medicine University of Iowa, Iowa City, IowaJohn Svaren, PhD Associate Professor Department of Comparative Biosciences, Waisman Center University of Wisconsin-Madison Madison, WIPeter I. Warfield, MD, MPH, FAAP Spring Valley Pediatrics Washington, DCLawrence Wrabetz, MD Professor of Neurology and Biochemistry Director, Hunter James Kelly Research Institute University at Buffalo, Buffalo, NY

Jonah Berger – Business Owner, The Rhythm Within Gregory Carter, MD, MS – Physiatrist Bob DeRosa – Marketing/Creative Consultant Katy Eichinger, PT, DPT, NCS – Physical Therapist Tim Estilow, OTR/L – Occupational Therapist Shawna Feely, MS, CGC – Genetic Counselor Sarah Kesty, MA – Special Educator Sean McKale, CO, LO – Orthotist Bethany Meloche – Youth Director

Board of Directors

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David Misener, BSc, CPO, MBA – Orthotist Elizabeth Misener, PhD, LMSW – Social Worker James Nussbaum, PT, PhD, SCS, EMT – Physical Therapist Sabrina Paganoni, MD, PhD – Harvard Medical School Professor Glenn Pfeffer, MD – Orthopedic Surgeon Greg Stilwell, DPM – Board Certified Podiatrist Carly Siskind, MS, CGC – Genetic Counselor David Tannenbaum, LCSW – Psychotherapist Amy Warfield, PT, DPT, NCS – Physical Therapist

CMTA branches are the main touchpoint between the national organiza-tion and its members: The CMTA provides members education and sup-port and members raise funds and awareness for the parent organization.

At the beginning of 2015, we renamed our Support and Action Groups CMTA Branches in recognition of the vital and organic role they play in fur-thering our mission. By year’s end, there were more than 70 branches in the United States and Canada providing help and hope to memberswho met regularly to share their own personal experiences and hear from

leading clinicians and scientists provided as guest speakers by the CMTA.

The branches also raised awareness and funds for the CMTA. Awareness Month 2015 was the biggest ever as more than 500 people participated in 34 All-Star

events, walking, rolling, running and biking “4CMT.” They raised an amazing$218,000 in the process.

In addition to the All-Star events, a record 28 states proclaimed September 2015 CMT Awareness Month, as did scores of cities and counties. Thirty people signed up to “Go Blue 4 CMT,” dying their hairand raising more than $20,000 for the CMTA. Community members also came up with other creative ways to raise awareness about CMT: They decorated cakes, wrapped trees in blue ribbon and put the letters “CMT” up in lights for all to see.

All in, CMTA branches contributed an astounding total of $624,373 to the CMTA and STAR in 2015.

CMTA Center of Excellence Cedars-Sinai Medical Center (California) Children’s Hospital of Philadelphia (Philadelphia) Connecticut Children’s Medical Center (Farmington, CT) Harvard University (Massachusetts) Johns Hopkins University (Baltimore) Lucile Packard Children’s Hospital at Stanford (Palo Alto) Nemours Children’s Hospital (Orlando) Stanford Hospital (Stanford) University of Iowa (Iowa City) University of Miami (Florida) University of Michigan (Michigan) University of Minnesota (Maple Grove) University of Pennsylvania (Philadelphia) University of Rochester (New York) University of Utah (Utah) University of Washington (Seattle) Vanderbilt University (Nashville) International The Children’s Hospital (Sydney, Australia) The Nat’l Hospital for Neurology & Neurosurgery, (London, England) C. Besta Neurological Institute (Milan, Italy)University of Antwerp (Belgium)

CLINICAL DIRECTOR Drs. Robert Baloh and Richard Lewis Dr. Sabrina Yum Dr. Gyula Acsadi Drs. William David, Florian Eichler, Vera Fridman and David Chad Dr. Thomas Lloyd Dr. John Day Dr. Richard Finkel Dr. John Day Drs. Michael Shy, Laurie Guttman and Nivedita Jerath Dr. Mario Saporta Dr. Sindhu Ramchamdren Dr. David Walk Dr. Steven Scherer Dr. David Herrmann Dr. Nicholas Johnson Drs. Michael Weiss and Leo Wang Dr. Jun Li

Dr. Joshua Burns Drs. Mary Reilly and Francesco Muntoni Dr. Davide Pareyson Dr. Jonathan Baets

CMTA Branches

�e CMT Clinical Centers of ExcellenceImproving the quality of life for those with CMT is one of the CMTA’s primary missions and one way we accomplish this mission is by sponsoring patient-centric, multi-disciplinary CMT clinics, staffed by some of the highest quality CMT clinicians and researchers in the world. Through these CMTA-designated Centers of Excellence, children, adults and families affected by CMT can be assured of receiving comprehensive care by a team of CMT experts.

The Centers of Excellence will soon become even more important as the CMTA begins clinical trials for candidate therapies. The success of these trials will largely 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, and much of that information will be supplied by the Centers of Excellence. The Centers roughly correspond to the 20 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 of Excellence are part of the Inherited Neuropathies Consortium (INC), which is funded by the CMTA, the MDA, and the National Institutes of Health. Worldwide, more than 7,700 patients with CMT have been enrolled in protocols during the past three years, and their data, de-identified to protect patient privacy, is housed in a common repository. As a result of this collaboration, a new CMT evaluation scale for children has been established, along with a new evaluation system for adults, and an infrastructure has been developed to perform natural history studies and clinical trials for CMT.

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Education & Awareness

Resources

PUBLICATIONS

• The CMTA Report - First published in 1987, our quarterly newsletter provides patient education and practical support.

• CMTeen – A quarterly online magazine by, for and about the 13- to 19-year-old members of the CMT community.

• The CMT Guide to Orthotics - Developed in partnership with the Lower Extremities Review spe-cifically for individuals with CMT, this guide provides valuable information about orthotics and AFOs and is intended to educate the CMT community as well as practitioners who create and fit orthotics and AFOs.

• Genetics of CMT - An in-depth look at the genetics of CMT, including family history, genetic testing and reproductive options by Shawna Feely, certified genet-ics counselor and CMTA Advisory Board member.

• Managing Neuropathic Pain - CMTA Board Member Steven Scherer, MD, PhD, discusses the causes of neuropathic pain and provides detailed infor-mation about the medications used to treat it.

CMTA WEBINARS Since Dr. Michael Shy presented “Everything You Wanted to Know About CMT and More” in September 2013, the CMTA has been scheduling webinars on a monthly basis. Presenters cover a wide variety of topics intended to inform and educate everyone about CMT, from foot problems to bracing to finding CMT’s silver lining. Members have the opportunity to submit questions for speakers, watch live, or watch a recording at their leisure.

PATIENT/FAMILY CONFERENCES

The Charcot-Marie-Tooth Association is all about making connections—between patients and doctors, among the doctors and researchers who do the vital research on a treatment for CMT, and between pa-tients and other patients. Nowhere is this more evident than in the Patient/Family Conferences the CMTA holds each year, often in collaboration with a CMT Center of Excellence or multi-disciplinary CMT clinic.

These all-day conferences allow people with CMT and their families to get up-to-date information on the CMTA’s Strategy to Accelerate Research (STAR) from the scientists leading the effort to find treatments for CMT. They also feature presentations from local clinicians and health care providers on topics such as the causes and diagnosis of CMT, physical and oc-cupational therapy, orthotics and bracing, orthopedic surgery, genetic counseling and more. Just as impor-tantly, the Patient/Family Conferences allow people who have CMT to connect with other people who have CMT, some of them for the first time in their lives.

ONLINE EDUCATION AND SUPPORT

The CMTA also provides education and support through a robust online community. The CMTA launched a new website in 2015 (with a new, user-friendly Resource Center) that includes a revamped, private Emotional Support Group moderated by a psychotherapist with CMT. Our Facebook community has grown to more than 25,000 followers, who take part in a constant stream of conversation, posting hundreds of comments daily. In addition, the CMTA has 2,100 Twitter followers; 1,500 Pinterest followers; and 400 LinkedIn professionals. In the summer of 2015, an intern started an Instagram account to help the CMTA reach a younger demographic and it now has 450 followers. And in an online Awareness Month campaign, more than 700 people took to Facebook to proudly proclaim to the world that each was “1 in 2,500.” The resulting photos were gathered in a huge album that illustrates that community members truly are one big family, con-nected to one another and committed to finding a solution to CMT together (on.fb.me/1gSRi2D).

In addition to funding research, the CMTA delivers high-quality education and awareness resources to the CMT community. We host two full-day Patient/Family Conferences annually, with additional half-day conferences nationwide. We publish educational materials for people living with CMT, for parents, for teens and for clinicians. We provide support, education and awareness through our 70 branches and our robust virtual presence. And we enlist partners whose services improve the quality of life for those with CMT. Members can access resources by calling 1-800-606-2682 or visiting www.cmtausa.org.

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In 2008, the CMTA launched STAR as a strategic research program to maximize breakthroughs in genetics and dramatically speed up the pace of CMT research.

The opportunities associated with STAR stem from the fact that the causes of CMT have been pinpointed, leading to the identification of more than 80 specific gene defects.

More importantly, the fact that these genetic mutations can be replicated in laboratory models and grown as tissue cultures opens an extraordinary window of opportunity to

develop treatments and cures for CMT in the immediate and foreseeable future.

Working with the preeminent thought leaders and institutions within the inherited neuropathy community, the CMTA is at the forefront of the advancement of CMT research, the creation of clinical standards of care and the development of therapies to treat and cure CMT. Through these strategic relationships and programs, not only is the CMTA able to stimulate the advancement of collaborative CMT research and

clinical care, but it is also able to provide essential information for outreach and education to the national CMT patient and health care professional communities.

The scientists conducting research for the STAR program have been chosen from an international body of the world’s most accomplished medical pioneers. The STAR program’s unique character stems from the willingness of the scientists to come together to advance CMT

research as a team, sharing and communicating ideas, discoveries and research findings. Scientists in this international network are each working on fundamental biological aspects of this disease – leveraging and promoting their unique expertise in a collaborative manner is what sets the STAR program apart from any other CMT-related research effort.

A STAR Is Born

CMTA STARThe Strategy to Accelerate Research

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CMT1X

CMT2A

CMT2E

AssayDevelopment

DrugScreening

Pre-Clinical

Pre-IND

ClinicalPhase 1

ClinicalPhase2

LaboratoryModels

CMT4

For each type ofCMT, develop arobust populationwith offspring thatexhibit symptoms and can be usedto test candidatepharmaceuticals.

Build cellular assays,reproducing cells with each type ofCMT that can beused for the rapidtesting of manydifferent chemical compounds.

Screen the cellularassays using the chemical librariesat the National Institutes of Health and major pharmaceuticalcompanies.

Test the candidatedrug compounds bygiving doses tothe symptomaticlaboratory models and measuringtheir improvement.

Test the compounds for dosage, toxicityand viability in private and academiclaboratories todetermine the exactdosage that will improve the rootcause of CMT.

Conduct pre-clinicalphase 1 human trials.A small group ofstrong, healthy peoplewithout CMT will take the dose ofthe compounds totest for human sideeffects and toxicity.

Conduct pre-clinicalphase 2 trials. Recruited throughthe CMT Centers ofExcellence, small groups of people with type-specificCMT will participatein pharmaceuticaltrials to determinethe effect the drug will have on CMT.

CMT1B

CMT1A

The Strategy to Accelerate Research (STAR)

The CMTA is aggressively �ghting to �nd a pharmaceutical treatment, and, ultimately, a cure for all types of CMT. We currently have protocols for developing treatments for the types of CMT that affectapproximately 90 percent of all people with CMT. The chart below shows the status of each of those projects.

CMT TYPE 1 CMT1 is a demyelinating peripheral neuropathy characterized by muscle weakness and atrophy in the extremities, sensory loss and slow nerve conduction speed (typically 5-30 meters per second). It is usually slowly progressive and often associated with a high- arched foot deformity and foot drop. Symptoms often present between the ages of 5 and 25 years.CMT TYPE 2 CMT2 is an axonal (non-demyelinating) peripheral neuropathy characterized by muscle weakness and atrophy in the extremities, mild sensory loss and normal or near-normal nerve conduction speed. CMT2 shows extensive clinical overlap with CMT1, although it is often less severe.CMT TYPE 4 CMT4 is a group of progressive motor and sensory axonal and demyelinating neuropathies. It is distinguished from other forms of CMT by its autosomal recessive inheritance. Affected individuals have the typical CMT phenotype of muscle weakness and atrophy in the extremities, some associated sensory loss, and, frequently, the high-arched foot. CMT TYPE X CMT1X is so named because it is linked to the X chromosome, and it is considered to be an X-linked dominant trait. It is passed from a carrier female to her son. There is no male-to-male inheritance, but an affected male will pass the defective gene to all his daughters. CMT1X is characterized by a moderate to severe motor and sensory neuropathy in affected males and, usually, mild to no symptoms in carrier females. Sensorineural deafness and central nervous system symptoms can occur in some families.

CMT SUBTYPES

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Protocols for Developing Treatments

The CMTA is collaborating with the New York Stem Cell Foundation (NYSCF) to develop cellular models of CMT for individual patients. A bank of skin cells from patients with different CMT disorders, and in particular CMT1A, has been assembled at the University of Iowa.These cells are being provided to the NYSCF so that they can be transformed into induced pluripotent stem cells (iPSCs), which can then be further differentiated into mature Schwann cells or neuronal cells and studied. The CMTA is also collaborating with Dr. Gabsang Lee (Johns Hopkins Medical Center) and Dr. Robert Baloh (Cedars-Sinai Medical Center), who are performing research aimed at determining the optimal means of creating fully differentiated human patient Schwann cells from the iPSCs.

Building Human Cellular

Assays for Enhanced Drug

Discovery

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STAR – CMT Type 1A CMT Type 1A is caused by the dupli-cation of the Peripheral Myelin Protein 22 (PMP22) gene, which leads to the demyelination of the peripheral nerves. Our partnership with Genzyme, a Sano-fi company, has identified a handful of compound series for treating CMT1A. Additionally, five other pharmaceutical companies are in early testing of com-pounds believed to have positive effects on CMT1A. We have improved the pro-cess for transforming adult human stem cells into Schwann cells (the cells that make myelin), preparing for a human cell assay. Laboratory models continue to reproduce robustly and the clinical data base is expanding. Together, the STAR team will forge ahead into preparing for clinical trials for CMT1A.

STAR — CMT Type 1B The CMTA initiative to develop a CMT1B project is focused on creating report-ers of cellular pathways suspected of a causative role in CMT1B, and being done via collaboration of laboratories at the University of Iowa and the NIH (NCATS). Through the work of Dr. Brit-tany Wright at the NIH, three cellular assays and laboratory models are un-der development, and adult stem cell development is underway. In addition, a further effort to develop animal models of CMT1B is now underway at the Uni-versity at Buffalo.

STAR — CMT Type 1X Dr. Rudolph Martini at the University of Würzburg, Germany, has been inves-tigating whether human mesenchymal stem cells can ameliorate the neurop-athy in a genetically authentic rodent model of CMTX. This is a novel type of treatment for CMT as it seeks to modi-fy the immune system to improve nerve function. His laboratory has also tested in this model compounds obtained via a pharmaceutical collaboration, and thought to target immune processes likely affecting CMTX disease progres-sion. Early positive results from anti-inflammatory compounds have been demonstrated in laboratory models and further investigation is underway.

STAR — CMT Type 2A CMT2A is caused by dominant mu-tations in MFN2. The STAR team has developed two viable, robust laboratory models for two mutations. Characterization of the models is un-derway and when complete will be poised to test potential compounds. Assays that can measure rescue of the 2A defect at a cellular level are underway in preparation for a high-throughput screen.

STAR - CMT Type 2E CMT2E is caused by dominant muta-tions in the neurofilament light protein (NEFL). One result of the mutations is to prevent the neurofilament light proteins from assembling properly, resulting in the formation of aggre-gates or abnormal filaments. A team of 2E experts has met to discuss the pathway toward drug delivery. Lab-oratory models are established and are under validation, preparing for drug candidate screening.

STAR – CMT Type 4T A team of type 4 experts is being assembled to develop a pathway toward drug discovery. STAR’s first Type 4 project has been approved and is being documented for takeoff.

STAR Research Updates

Type 1A Samuel and Urijah Faulds, 2 and 5

Type 1B Lia O’Sullivan, 5

Type 1X William Stuhlmueller, 8

Type 2A Tessa Pate, 6

Type 2E Julia Beron, 16

Type 4 Paige Rodgers, 29

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The STAR Consortium’s work is broken down by disease area (CMT1A, CMT1B, CMTX, CMT2A, and CMT2E) and project teams consisting of academic labs and clinical centers, working together with alliance partners in consortium team efforts. Identifying mutations is an important first step in the process and the CMTA is helping to identify the mutation and type of CMT that Julianna has, which would lead to putting a STAR project in place to work toward a therapy. Julianna Snow, 5

CMT Typing Underway Capturing Grace Photography

Addex Therapeutics is collaborating with the CMTA to evaluate the efficacy of ADX71441 as a pharmacological agent in preclinical neurological and behavioral models of CMT1A and to assess its potential to impede the development of motor and sensory control defects associated with normal disease progression.

Genzyme, a Sanofi company, is collaborating with STAR investigators to leverage the Sanofi U.S. high-throughput screening facility in Tucson, Arizona. The first round of screening, which included compound libraries with more than 2 million small molecules, has been completed and additional screening is underway.

Ionis Pharmaceuticals is the leading company in antisense drug discovery and development, and is working with the CMTA to exploit a novel drug discovery platform that provides a direct route from genomics to drugs.

The NIH Molecular Libraries Program provided its complete library of 500,000 compounds for screening. The first round of screening has been completed and further testing of selected compounds in both rodent and stem cell models has begun.

The New York Stem Cell Foundation collaborated with the CMTA to develop a bank of induced pluripotent stem cell (iPSC) lines for a variety of neuropathy disorders of known genetic causation.

Pfizer-Neusentis provided a selected subset of the Pfizer Chemogenomic library for screening in the CMT1A project. The CMTA has completed screening several thousand of these compounds. A number of potential drug targets that regulate PMP22 expression were identified and are being further validated.

PsychoGenics, a leader in specialty preclinical contract research and drug discovery services, provides biomarker and behavioral testing support to the STAR network.

ReNovo Neural is a leading specialized service company that provides expert histological and pathological analysis for animal models of neurological disease. They support the CMTA via the characterization of new animal models of CMT and by evaluating the effects of experimental drug treatment in these models.

The Rare Diseases Clinical Research Network (RDCRN) is funded by the National Institutes of Health and the Office for Rare Diseases Research. INC is a multi-center clinical research consortium within the RDCRN created to address the following issues pertaining to CMT:

• As we near clinical trials, a clinical scale that is sensitive enough to measure successful outcomes needs to be refined;

• Patients with different kinds of CMT must be analyzed in a uniform manner so that high-quality clinical data is available to investigators developing clinical trials or studying the pathogenesis of CMT in humans; and,

• Researchers will have to identify genetic modifiers that contribute to phenotypic variability in patients with identical CMT mutations, even within the same family.

The INC database is critically important to complement the progress and promise STAR holds for an eventu-al therapeutic and in June 2015 NIH announced $5 million in renewed funding for INC.

The establishment of an international patient registry by the INC will make it possible for researchers to find new treatments, create new studies, and work for the improvement of all those living with CMT. The CMTA, along with the Muscular Dystrophy Association, CMT United Kingdom, and TREAT NMD (European Neuromuscular Network), are the partnering patient advocacy groups within the INC.

The CMTA is well positioned to facilitate patient recruitment and involvement in cutting-edge research

Rare Diseases Clinical Research Network

Inherited Neuropathies Consortium

�e (INC)

protocols. In addition, the CMTA’s participation provides its national community with exclusive in-formation and access to the latest research findings associated with clinical protocols and therapeutic developments.

International CMT Scientific Conferences

The CMTA was a founding sponsor and collaborator of the 1st International CMT Conference in 2003. The aim was to exchange new information and, equally important, to start novel collaborations and strengthen existing networks between European and North American research groups. With a plenary lecture and other lectures covering clinical, diagnostic, and basic research issues of CMT neuropathies, the International CMT Consortium meetings have been held regularly since then.

The 6th International CMT Consortium took place in Quebec City, Quebec, Canada in 2015. Scientists and clinicians from around the world came together to advance CMT research as a team, sharing and communicating ideas, discoveries and research findings.

Scientists in this international network are each working on fundamental biological aspects of this disease. Leveraging and promoting this unique expertise in a collaborative manner is what sets the STAR program apart from any other CMT-related research effort.

The STAR program has been funded solely by the CMTA.

Collaborative Partners

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Aetrex Worldwide, Inc., founded in 1946, is a global leader in pedorthic footwear and orthotics. It offers attractive shoes that feature extra depth and width to accommodate in-shoe orthotics or AFOs.

Allard, USA distributes the ToeOFF Family of carbon composite devices designed specifically to assist with foot drop, ankle instability and proximal neuromuscular weakness, all symptoms of CMT.

Balance Walking is an all-encompassing health and fitness program incorporating walking poles that can be done in as little as 15 minutes per day.

CosySoles makes microwave heated slippers that provide comforting warmth and the freedom to stay mobile to millions who suffer from cold and painful feet caused by peripheral neuropathy.

Foot Solutions is a leading international footwear retailer with more than 150 stores in 14 countries specializing in personalized assessments, stylish high performance footwear, custom-fitted, custom-crafted arch supports and accessories designed to help individuals live pain free.

GeneDx launched the Hereditary Neuropathy Panel, a genetic testing panel aimed specifically at testing for different types of CMT, in 2014. With 53 CMT-causing genes available in the Neuropathy Panel, GeneDx delivers an exact genetic diagnosis for 50-70 percent of people with symptoms of CMT.

Hanger Clinic has more than 1,300 clinicians specializing in the provision of orthotic and prosthetic solutions. Its teams annually deliver effective clinical systems, innovative technologies and outstanding customer service to more than 1 million patients at over 750 Hanger Clinic locations nationwide.

Invitae is a genetic testing company with a comprehensive panel for CMT, as well as autosomal dominant, autosomal recessive, X-linked and HNPP (Hereditary Neuropathy with Liability to Pressure Palsies) panels.

Union & Fifth raises money for non-profits by selling donated, gently worn women’s designer clothes.

Corporate Partners

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Never doubt that a small group of thoughtful, committed citizens

can change the world; indeed, it’s the only thing that ever has.

Margaret Mead

Thanks to the efforts of many, many people—from the 12-year old who makes and sells wooden lamps to raise funds to the scientists working tirelessly at their benches—the CMTA’s Strategy to Accelerate Research (STAR) is poised to transform the hope for a treatment for CMT into actual help for people who suffer with the disease. Our alliances with the NIH, the RDCRN, the NYSCF, PsychoGenics and a number of pharmaceutical companies are groundbreaking steps and are critically im-portant to our continued success. Just as important is the participation—financial and otherwise—of each and every member of the CMT community as we near clinical trials.

We ask that you join us by investing in our vision of a world without CMT and promise to do everything in our power to deliver a return on your investment. Please contact me to learn more about supporting STAR and the CMTA’s work.

The CMTA has always provided the CMT community with help for today

and hope for tomorrow.

Patrick A. Livney, CEO • pal@cmtausa.org (312) 750-9800 PO Box 105, Glenolden, PA 19036

1-800-606-2682 info@cmtausa.org • www.cmtausa.org