Measures of Success

The first clinical trial of a new therapy for myotonic dystrophy (DM) in affected patients launched in December 2014. In order to help promote success for this and future clinical trials, DM researchers are working hard to determine what can be measured in clinical trials that will best demonstrate whether a drug really works. To support these efforts, MDF held a science workshop in September 2014 during our annual conference. The workshop brought together more than 50 research experts and industry representatives from around the world to review where we are with respect to developing these measures for DM.

Two kinds of measurements are typically used in clinical trials:

1. "Clinically meaningful endpoints," which measure things that have real impact on a person's day-to-day life. Clinically meaningful endpoints are used to approve a drug.
2. "Biomarkers," which are an indirect way to measure drug impact that is clinically meaningful. For example, a blood measurement that changes as symptoms improve could be a biomarker.

Clinical endpoints and biomarkers may be used for many purposes in drug development, including:

• Identifying the most suitable patients for clinical trials
• Determining if a drug is affecting the disease
• Determining if the drug is working the way it is supposed to

The use of the right biomarkers and endpoints for the right purposes can greatly reduce the time needed to develop a new drug.

At the science workshop, Dr. Richard Moxley of the University of Rochester described the progress in measuring myotonia (a "stiffness of muscle" or inability to relax the muscle). For myotonic dystrophy symptoms, this is currently the best endpoint. The researchers also discussed the potential for developing new DM biomarkers, including:

• Biomarkers that measure how the disease is progressing in an individual
• Biomarkers that are closely linked to the cause of the disease
• Biomarkers that measure disease progression in the heart and the brain (central nervous system), two areas that can be very affected by DM
• Biomarkers that may allow the grouping together of people in whom DM is progressing in a similar way
• A new questionnaire developed to measure how severe people feel their DM disease symptoms are

The investigators agreed that a person’s degree of myotonia is the best biomarker we have at this time, and that it can be used to measure drug impacts in clinical trials, although the most suitable way to measure myotonia has yet to be worked out.

Drs. Charles Thornton of the University of Rochester, Tom Cooper of Baylor College of Medicine, Andy Berglund of the University of Oregon and Eric Wang of MIT are among the researchers looking at blood samples to determine how gene activity is increased or decreased and how genetic messages and proteins are processed in human cells. By identifying groups of genes where processing changes as the disease progresses, investigators may be able to determine if a potential therapy is having an impact. There has been a lot of progress in this area, but researchers are still trying to identify a group of genes whose processing is tied to disease progression. Also, it is difficult to measure changes the in heart and brain because it is difficult to obtaining tissue, so more measurement options are needed.

Dr. Gordon Tomaselli of the Johns Hopkins School of Medicine described various ways to measure changes in the heart, primarily be using equipment to view the heart as it beats. Some of the changes observed may indicate when a person with DM is going to develop a particular type of heart trouble. Looking at heartbeat patterns using echocardiograms (ECGs) and electrocardiograms (EKGs) could also be useful for measuring drug effects. Unfortunately, there is not enough documentation to use these measurements in trials yet.

Because it is difficult to obtain samples of brain tissue, researchers have developed different ways of imaging brain structures and activity to measure disease-related changes. Dr. John Day of Stanford University described several types of brain imaging techniques that show differences:

• Between people with DM and unaffected individuals
• In people with different levels of disease severity
• In measurements as the disease progresses

These imaging techniques could be very valuable in determining if a therapy could treat DM symptoms associated with the brain.

Dr. Peg Noupoulos of the University of Iowa described a long-term study in Huntington’s disease, a triplet-repeat disease like myotonic dystrophy, which resulted in the development of some very useful biomarkers for that disease. She drew parallels between the lessons learned in those studies and how they could be applied to a new long-term DM study that is currently being carried out through the Myotonic Dystrophy Clinical Research Network (DMCRN).

Dr. Darren Monckton of the University of Glasgow described biomarkers that could be used to identify DM patients with similar disease courses. The ability to do this may be important, particularly in a disease like myotonic dystrophy that progresses slowly and is variable (patients have different symptoms and progress at very different rates). By starting a trial with a group of patients who progress in a similar way, drugs can be tested in smaller groups of patients more quickly, potentially making the process of developing the drug much faster. This area of research is just getting underway.

Finally, Dr. Chad Heatwole of the University of Rochester described a survey tool he developed to determine how people with DM describe their own symptoms and severity. This “patient-reported outcome measurement tool” is being used in clinical trials and research studies, and so far looks like a promising way to use feedback from patients to measure whether a treatment is working.

As more potential DM therapies move into the drug development pipeline, the measurements being developed now will hopefully speed the testing and approval process, getting needed therapies to people living with myotonic dystrophy as soon as possible.

02/26/2015

Tackling DM from Basic Research through Clinical Care

Tetsuo Ashizawa, MD, better known as "Tee" to colleagues and patients, has focused his career on the search for treatments for myotonic dystrophy (DM). As one of seven primary investigators who will participate in the first clinical trial of a potential treatment for DM1, Dr. Ashizawa may be closer than ever to achieving that goal. Yet in addition to pursuing research with dedication and tenacity, he has also been committed to providing the best possible care to people living with DM. Dr. Ashizawa's engagement in myotonic dystrophy spans basic research, translational science, patient-oriented research and clinical care.

Originally trained in neuromuscular diseases, Dr. Ashizawa first became involved in DM as a basic researcher, working with a team at Baylor College of Medicine to hunt for the DM gene. "There were actually several teams working internationally to find the gene," said Dr. Ashizawa. "Interestingly, in 1992 the various research teams all had the same finding, which was identification of DMPK, the genetic mutation responsible for myotonic dystrophy type 1. It was an exciting time, and that was the beginning of our journey to find treatments and a cure."

Patients Play a Key Role with Researchers

In 1998, as Dr. Ashizawa was expanding his research efforts, he received an email that would broaden his perspective. Shannon Lord, the mother of two boys with juvenile-onset DM1, wanted to make a donation to advance DM research. She provided a grant to Dr. Ashizawa through the Hunter Fund, an account named after her older son and established by Shannon and her husband Larry to support DM research projects. The grant was the start of a long-term friendship between Dr. Ashizawa, Shannon and Larry Lord, and ultimately led to a DM scientific meeting organized by Dr. Ashizawa and including the Lord family. "It was so powerful," said Dr. Ashizawa. "Before this meeting, many in the scientific community only saw DM through a microscope. Now investigators could see and understand the human face of the disease. It was a real morale booster for everyone and provided a great deal of momentum to move our work forward."

By then Dr. Ashizawa had also co-founded the International Myotonic Dystrophy Consortium (IDMC) to bring together scientists and clinicians focusing on DM. Shannon Lord attended the third biennial IDMC meeting in Kyoto in 2001, serving in the role of patient advocate and introducing patient advocacy to the IDMC research community. By the fourth meeting, about one hundred patients and families attended, and the participation of a large number of patients at these international meetings has since become routine. Today, IDMC meetings provide a unique opportunity for global researchers, clinicians and patients to come together; IDMC 10 will be held next June in Paris, France. "Without patient involvement, we wouldn't be able to push forward on the research frontier," Dr. Ashizawa said.

Research Moves Out of the Lab

By 2011, DM science had progressed significantly in the development of potential treatments for DM1. Seven research and clinical institutions around the country are currently preparing to launch the first clinical trial in affected patients to test the efficacy of an antisense oligonucleotide (ASO) therapy, DMPKrx, in people affected by DM1. The University of Florida (UF) will serve as one of these sites, with Dr. Ashizawa as the Primary Investigator for the institution.

Dr. Ashizawa has recently started a project looking at DM1 patient-derived, induced pluripotent stem cells (iPSCs), which can be developed into different cell types needed for research, e.g. muscle, heart, or even brain cells. These cells can help researchers understand how DM affects different body systems and causes disease symptoms. While the clinical use of these cells may be a long way off, iPSCs have a more immediate and critical function as a platform for the screening of compounds to find drugs that have therapeutic potential in DM1. "It's a very exciting time in DM research," Dr. Ashizawa says.

Providing Multidisciplinary Care in the Clinic

In addition to his research projects, Dr. Ashizawa oversees the clinical program at the University of Florida. Patients benefit from a multidisciplinary team of doctors that includes cardiologists, anesthesiologists and geneticists. "We help patients access any clinical trials for which they may be eligible," he says. "And when new treatments become available we are committed to helping our patients access them as soon as possible."

Dr. Ashizawa has published over 190 research papers and 35 book chapters. He is currently Executive Director at the McKnight Brain Institute at UF and Professor and Chair of the Department of Neurology at the UF College of Medicine, and he serves on MDF's Scientific Advisory Committee. With Drs. Maurice Swanson and S.H. Subramony, he has recruited Dr. Laura Ranum to UF and is in the process of recruiting a handful of other key DM investigators to build one of the strongest DM research teams in the world. "We are very hopeful about the research and treatment possibilities on the horizon. We have a distance to go and there are many questions to answer, but we won't stop working," says Dr. Ashizawa. "We are dedicated to our patients and to collaborating with them to find a cure."

12/09/2014

Dahlqvist et al
European Journal of Neurology

Dr. John Vissing and his colleagues at the University of Copenhagen recently tracked a group of 68 adults with myotonic dystrophy type 1 (DM1), measuring their endocrine function change over 8 years.  The authors examined bloodwork for many endocrine dysfunctions including diabetes (HbA1c blood test), hyperparathyroidism (PTH blood test), and androgen insufficiency (testosterone blood test in men), and found that these dysfunctions became more common over time in people with DM1.  The authors recommend that doctors treating people with DM1 should screen for endocrine functions regularly, as the dysfunctions occurs more frequently in DM1 than the general population.

Click here to read the abstract for this study.

Click here for a PDF of this paper.

10/16/2014

The University of Iowa Hospital (UIHC) has a 20 year-long history of treating patients with myotonic dystrophy (DM). This year UIHC plans to build upon its efforts to serve DM patients by offering a multidisciplinary DM clinic under one roof in late fall of 2014.

The clinic will be staffed by providers from neurology, cardiology, psychiatry, physical therapy, occupational therapy, dietary services, social work, genetic counseling, speech therapy/swallow therapy, and sleep medicine. The multidisciplinary clinic aims to provide a patient-centered, comprehensive team-based approach that will coordinate care across disciplines, providing easily accessible services for DM patients. 

“Our goal in creating the DM clinic at UIHC is to improve the quality of life for DM patients,” says Laurie Gutmann, MD, Clinical Professor of Neurology, and Director of the Myotonic Dystrophy Multidisciplinary Clinic. The planned DM clinic will allow patients to schedule half-day appointments to see multiple specialists in one location. “We want to be proactive in our approach to managing patients’ symptoms. Providing ease of access to specialists who see DM patients on a regular basis, and who understand the complexity of DM, will help in meeting the needs of DM patients,” adds Dr. Gutmann. 

In addition to improving access to services for DM patients, the UIHC DM clinic will be better situated to streamline DM research at the facility, enabling investigators to establish research and clinical trial protocols quickly and effectively. An improved understanding of the progression of the disease will enable the team to measure the effectiveness and possible side-effects of future clinical trials of drug therapies.    

At UIHC, Peg Nopoulos, MD, Professor of Psychiatry, Neurology, and Pediatrics and Vice Chair for Research, Department of Psychiatry, is using brain imaging and neurogenetics to better understand the heredity and neurological progression of the disease. “By following changes in the brain we hope to anticipate symptoms before they occur, and to understand how the brain’s molecular biology relates to DM symptoms.” says Dr. Nopoulos. Sarah Tighe, MD, Assistant Professor Department of Psychiatry at the UIHC DM clinic, is also investigating brain-based features of DM, such as depression, anxiety, and memory disturbances.

The launch of the UIHC multidisciplinary DM clinic adds to the growing interest in DM care and potential therapies. While the multidisciplinary DM clinic at UIHC doesn't launch until late fall, DM specialty services are currently available. To make an appointment at the UIHC DM clinic, call Erin Springer at (319) 356-8958. For pediatric information and appointments, contact Christina Trout at (319) 356-4017.

If you are attending the 2014 MDF Annual Conference, you can hear Dr. Tighe speak in the session, “DM and Emotional Health: Depression and Anxiety.” If you can’t attend the conference, you will be able to watch the session via MDF’s livestream broadcast. View the 2014 MDF Annual Conference web content for more information about the livestream broadcast. You can also view conference sessions starting in late September online in our Digital Academy.

09/02/2014

Expanding the Scope of DM Research

A little over three years ago, MDF awarded a grant to support the establishment of the first-ever Myotonic Dystrophy Clinical Research Network (DMCRN). Based on input from university researchers and pharmaceutical companies, MDF felt it was critically important to expand the scope of DM research and prepare for upcoming trials of potential treatments.

Developing Targeted DM Treatments

A targeted treatment is one that is tailor-made and specifically designed for a particular disease. Targeted treatment development is a lengthy process that involves at least nine different steps. The targeted treatment development process for myotonic dystrophy was started when the DM1 genetic mutation was discovered in 1992, and continued with the identification of the DM2 mutation in 2001. The pace of scientific discovery has accelerated significantly in recent years. Isis Pharmaceuticals is scheduled to begin testing the first targeted treatment in DM patients later this year, with more options from other industry members to follow in the future. While it is likely that progress in treating DM will come in several steps rather than one giant leap, and the best treatment approach may involve a combination of drugs to best meet individual patient needs, this accelerated progress has been very encouraging.

Why We Need the Network

Testing a new drug involves a series of studies, called clinical trials, that are designed to answer several key questions:

• Does the drug have a beneficial effect? If not, why not?
• What benefits can the drug provide and what are the potential side effects?
• If the drug is effective, what is the best dose? How long does it last? When should it be started?

To answer these questions we need reliable testing procedures with proven accuracy, and a group of research sites to monitor the treatment and carry out the measurements. The testing procedures must be carefully selected and standardized, and the teams at each site should have extensive experience using the procedures to ensure that test results are consistent. The Clinical Research Network is focused on making this happen.

Goals of the DMCRN

1. To develop research teams at each site, with team members who are committed to myotonic dystrophy and experience with the research procedures.
2. To learn more about DM - there is still much we don't know. For example, researchers do not have a detailed understanding of why myotonic dystrophy is so variable from person to person, what controls the size of the repeat expansion, or what exactly leads to the muscle weakness, gastrointestinal symptoms, or central nervous system effects.  Answering these questions will help researchers undestand how people respond to therapies and may lead to the design of new targeted treatments.
3. To collect additional data needed for clinical trials, including:

• ​Outcome measures (how the success of a trial will be measured)
• Disease progression (how and why DM becomes more severe over time)
• Biomarkers (something in a cell or body tissue that can help indicate the presence of a disease like DM, and help measure changes in that disease due to the effects of a drug)
• Endpoints (outcomes of drug treatment that demonstrate whether a drug is effective, e.g. improved strength, interrupted disease progression, etc.)

A major focus in setting up the DMCRN was making sure that all researchers in the Network would have free and unrestricted access to the data collected through DMCRN studies, and that they would all be able to publish the results of these studies. In addition, DMCRN stakeholders committed to making access to study results available to researchers across the US and the world, in both the academic sector and in industry. The objective with these Network design decisions was to help lower barriers to advancing DM science and research, and continue the remarkably collaborative and friendly research environment that has been a hallmark of the DM research community to date.

DMCRN Members

The DMCRN is comprised of eight medical centers with significant proficiency in myotonic dystrophy clinical care and research. The current DMCRN sites are:

1. University of Florida McKnight Brain Institute - Dr. S. Subramony,  Primary Investigator
2. University of Kansas Medical Center Research Institute - Dr. Richard Barohn, Primary Investigator
3. Ohio State University Medical Center, Dr. John Kissel - Primary Investigator
4. Stanford University School of Medicine, Dr. John Day - Primary Investigator
5. University of Rochester - Drs. Richard Moxley and Charles Thornton, DMCRN Primary Investigator
6. National Institutes of Health - Dr. Ami Mankodi, Primary Investigator
7. University of Utah - Dr. Nicholas E. Johnson - Primary Investigator
8. Houston Methodist - Dr. Tetsuo Ashizawa - Primary Investigator

The University of Rochester is the lead DMCRN site, with Dr. Charles Thornton as the DMCRN PI. Data from the DMCRN studies are processed in the Data Management Center at Rochester, as is analysis of tissue and blood samples from the current DMCRN study. While Dr. Thornton and the University of Rochester initiated the current DMCRN research study, future studies may originate from any of the sites. Other DMCRN sites may be added in the future.

DMCRN Funding

DMCRN financial support has come from a broad consortium of stakeholders in the DM community. These include MDF, along with other patient advocacy organizations such as the Marigold Foundation and the Muscular Dystrophy Association; the National Institutes of Health (NIH) through their support of the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center in Rochester; and industry, through support from pharmaceutical company Biogen Idec.

DMCRN Activities and Progress

Since the Network's launch last year, DMCRN researchers have initiated a number of projects to achieve the goals described above. Standardized equipment to measure myotonia and muscle strength is now in place at all DMCRN sites, and training sessions for research coordinators and evaluators have been carried out. Research teams at each site now have experience with specialized measurements of muscle strength and myotonia and the procedures used to obtain biopsy samples of muscle tissue. A study of biomarkers was completed and published in December 2013 and a study to select biomarkers for use in clinical trials is currently underway. The Network has launched a longitudinal (long-term) study to track the progression of DM over time in 100 patients.

What's Next

The DMCRN is moving forward quickly, and meeting the interim goals established for the first 3-5 years. Equally hopeful, the drug development pipeline continues to grow with additional pharmaceutical companies engaging in DM treatment development. The establishment of the DMCRN and other infrastructure projects like the Myotonic Dystrophy Family Registry, the University of Rochester FSHD and DM Registry, and DM biobanks are demonstrating to pharmaceutical and biotech companies that myotonic dystrophy is a good bet for drug development. Overall, DMCRN members are very pleased with the progress they have achieved with the Network. In the words of DMCRN Primary Investigator Dr. Charles Thornton, "The pieces are falling into place, and we hope that the DMCRN will prove to be a historic partnership of industry, advocacy groups, academic researchers and government to develop a truly effective treatment for myotonic dystrophy."

07/23/2014

What is the Stanford Biobank?

The Stanford Myotonic Dystrophy Biobank is a collection of biological samples from donors for scientific research. The Biobank stores samples such as blood, muscle, skin, spinal fluid, and other clinical specimens. The Biobank collects tissues from people with myotonic dystrophy, related neurological disorders, and unaffected family members. Samples can be collected with your consent during routine clinic visits, during scheduled surgical procedures, or after death with your family's consent. The Biobank then organizes and stores these samples so that they can be shared with scientists throughout the world for research. These samples are tremendously valuable in helping determine how myotonic dystrophy affects the body, which will in turn help develop meaningful treatments. This resource facilitates the involvement of subjects with myotonic dystrophy to assure researchers have access to necessary samples.

How do I enroll?

Enrollment in the Stanford Myotonic Dystrophy Biobank is relatively easy, and requires you to fill out two forms. The first form is the Intended Donor Information Form containing your personal information, and contact information for your next-of-kin and primary healthcare provider. The second form is the Research Consent Form which allows you to formally state your intent to allow the Stanford Neuromuscular Program to collect your tissue samples for research purposes. Individuals who intend to have their remains donated through an autopsy after their death should include information about their funeral home on the Intended Donor Information Form; the mortician can be very helpful in facilitating an autopsy. The Research Consent Form contains both your signature, and the signature of your next-of-kin, which will help assure your family of your intent. For an autopsy to occur, however, a consent form from the institution performing the autopsy will need to be signed by the next of kin after death. The Biobank recommends that you make several copies of these signed forms and store them in your personal records. You should also give copies to your family, next-of-kin, primary healthcare provider, and designated funeral home. The Biobank team also recommends that you include your Research Consent Form in any medical directive, will or living will. You should mail Stanford the original copies of both forms. If any of the contact information changes, Stanford asks that you update them by emailing or calling the non-emergency contact information below.

How will my donated sample be used?

The donated samples will be stored at Stanford for future research. Qualified researchers who require samples will apply to the Biobank, submitting a description of their research project and proof of institutional approval. Samples given to researchers will have all personal identifying information about the donor removed, and will simply include information about the medical condition of the donor (see privacy question below for more information). Stanford will not be able to provide families with information about where or how individual donor specimens are used, but is happy to provide general information about projects and publications that have used Biobank samples.

What are the benefits of enrolling?

Myotonic dystrophy is relatively uncommon, so researchers have difficulty procuring the samples they need for investigations. By donating to the Stanford Myotonic Dystrophy Biobank, you will help researchers make scientific discoveries that may ultimately benefit individuals with the condition that affects you and your family. The Biobank research team will take care of all arrangements, and any costs of donation, once you have notified them.

How will my privacy be protected?

All identifying information recorded in the Intended Donor Information Form and Research Consent Form will be stored at Stanford and not released to any other researchers. When samples arrive at the Biobank, they are labeled with a unique identifying number. The Biobank team will ask for specific medical information that will be associated with the specimens, but only Dr. Day and his direct team will have access to the identifying information linked to the unique ID number. Samples shared with researchers will only have the ID number, description of the type of sample/tissue, and characterization of the donor's condition. If at any time you no longer wish to be enrolled in the Biobank, you can contact the Biobank by email or phone and your information and samples will be immediately removed from the Biobank system.

How do I donate?

If you are scheduled for a procedure you believe may produce samples for donation, you can email or phone the non-emergency Biobank contact below to make arrangements for specimen collection. If you are the next-of-kin, primary healthcare provider, or funeral home representing a person enrolled in the Stanford DM Biobank for autopsy donation and you believe death is imminent, contact one of the Biobank staff members listed below. A single phone call is typically all you will need to make; the Biobank team will take care of the rest of the arrangements. After the family member’s death, the next of kin will have to provide consent for the autopsy at the institution providing that service. The autopsy is performed as soon after death as possible, usually within 24 hours. After the autopsy is completed, the remains are returned to the mortician. Care is taken throughout the procedure to preserve normal appearance, so that there is no restriction on the type of memorial service available to the family.

Who can I contact for more information? 

If you have questions, contact the Biobank team using the information below. 

Contact Email: stanfordbiobank@lists.stanford.edu

Biobank enrollment: (650) 497-9807

Dr. Day’s Lab: (650) 723-9574

For urgent matters you may call: 

Katharine Hagerman, PhD
Lab: (650) 723-9574

Shirley Paulose, MS
Office: (650) 724-3792

John W. Day, MD, PhD
Office: (650) 725-7622

 05/16/2014

Myotonic community members often contact the Foundation with questions about genetic testing. Their questions range from how to find facilities that conduct genetic testing for myotonic dystrophy (DM) types 1 and 2 to whether or not they should be tested and how to assess the benefits and risks of having a genetic test.

The question of whether or not to be tested is best answered in partnership with a physician or genetic counselor who understands your family history, your personal circumstances and reasons for exploring genetic testing. Implications associated with DM genetic testing are financial as well as emotional. For this reason, the question of whether to get genetic testing for DM should be considered carefully.

We spoke with Carly Siskind, MS, LCGC, senior genetic counselor on the Stanford University Neuromuscular Disorders Team about the pros and cons of testing and the impact it can have on issues such as insurability.

What do you do as a genetic counselor?

Usually people are referred to me by a specialist such as a neurologist. Sometimes individuals call my office directly. My job is two-fold: to provide basic information about genetics and the implications of testing, and to be the person between the doctor and the patient to help interpret “doctor speak.”

I’d like to emphasize that while genetic testing can provide definitive answers with regard to the presence of disorders like DM, the decision of whether to pursue genetic testing is a personal one with significant potential impacts, both positive and negative. I encourage anyone considering genetic testing to consult with his or her physician or qualified medical professional first, and to consider working with a genetic counselor; we can be helpful in navigating this process.

Do most people understand how DM gets passed along?

Most people I’ve met with to discuss myotonic dystrophy are already fairly well educated on the topic, but I find it helpful to go through some of the basics nonetheless. DM is a complicated disease; for instance, if someone has not inherited the CTG (DM1) or CCTG (DM2) repeat expansion and both copies of this gene—one from each parent—are in the normal range, then he or she won’t develop DM or pass it on to future generations. Only if someone has the expansion will that person potentially experience symptoms or risk passing DM on to his or her children.

What are some of the pros and cons of genetic testing for DM?

If a person isn’t experiencing any DM symptoms but has a family history of DM, it is important to consider the consequences of being tested. Insurability is probably the biggest concern. Even if someone doesn’t have symptoms or a DM diagnosis, if his or her genetics indicate that there is potential to develop DM in the future, it can—and probably will—impact that person’s ability to secure life, disability and long term care insurance. While it is sometimes possible to get this insurance with a family history of DM, it is nearly impossible to get it with a diagnosis, and a diagnosis might still delay access to health insurance.

Because of this, we generally recommend that people think about setting up insurance policies prior to being tested in case their test comes back positive. Unlike health insurance, there’s no federal protection against discrimination for these other three types of insurance.

What are some of the reasons to consider getting tested?

Having a genetic test for DM provides information that, should the test result be positive, can assist the attending physician in anticipating complications, and can also allow for easier insurance approval for other diagnostic testing such as an EKG to detect arrhythmia, a common issue for those with DM. While clinicians typically use the repeat number to help inform diagnosis and care considerations, I have found that people in the community like to use this number as a way to help tell their personal stories and create connections to others living with DM.

Is the DM genetic test widely available? Where can people find a lab if they want to be tested?

There are a number of labs that conduct testing for DM, including academic or institutional settings such as Baylor College of Medicine, etc., and for-profit corporations such as Athena Diagnostics and Medical Neurogenetics. There are a number of labs in the U.S. that offer testing for DM. Prices can vary considerably depending on the lab and whether someone is being tested for DM1 or DM2. I would advise people to do their research in advance, and call their insurance plan before testing to see if the insurance company will cover a particular lab.

Insurance plans may request a CPT code to consider a request for genetic test reimbursement. CPT stands for Current Procedural Terminology and is generated by the American Medical Association for coding, billing and insurance purposes. CPT codes can be found on each lab’s website and are publically available.

The insurance company may also want an ICD-9 code, which is a diagnosis code used by the US Centers for Disease Control (CDC) and other international public health agencies to assist with disease reporting. ICD stands for International Classification of Diseases. The current diagnostic code for myotonic dystrophy is 359.21. Updated ICD-10 codes will be implemented in October 2014 and at that time the DM code will change to G71.1.

Insurance companies should be able to explain what percentage of the cost of a DM genetic test they will cover. Individuals with very low incomes can sometimes qualify for financial assistance programs.

What does the testing involve?

It requires a blood draw. It takes about three weeks to get the results, although timing varies from lab to lab. For those with DM in their family who choose not to get the genetic test, I recommend talking with their doctor about scheduling an EKG every year or two, at least until they’re 18 years old. While an abnormal EKG may not imply a DM diagnosis, when coupled with a family history of DM, an abnormal EKG should direct the physician to conduct additional follow up testing.

What do you discuss with individuals who have a family history of DM and are considering getting pregnant?

Reproductive options are definitely an issue we discuss when appropriate. The risk of having a child born with DM is 50/50 for each pregnancy. In this situation, prospective parents can think about options for testing the pregnancy. Tests can be run to look for the repeat expansion at 10-12 weeks of pregnancy through chorionic villus sampling (CVS) or by amniocentesis after 15 weeks.

It’s important to note that the expansions can grow and change as the baby develops. The number of repeat expansions found by CVS or amnio are not necessarily going to be the same number that the baby has when it is born, so those numbers can be used to determine whether the baby will be affected by DM, but not to predict disease severity. The implication for this type of testing would be that the parents can decide if they want to proceed with the pregnancy.

For those who don’t want to go that route, there’s also the option of pursuing in vitro fertilization (IVF) and getting the appropriate testing done before implantation to ensure the DM genetic mutation has not been passed along to the baby. This pre-implantation genetic diagnosis (PGD) test is done after the sperm and egg are fertilized and have developed up to eight cells. At that point, one or two of those cells are removed and tested for the DM repeat expansion. Doctors can then transfer to the mother only embryos that don’t have the expansion, so the disease won’t be passed on.

Generally, it can be assumed that about 50% of these fertilized eggs have the expansion. IVF/PGD is a very expensive option, usually costing at least $20,000 per cycle so, depending on state and insurance plan, prospective parents may or may not be able to get some help with these costs.

Note: Athena Diagnostics offers qualifying patients a substantial discount on its regular price for clinical laboratory services. If you cannot afford to pay for testing ordered from Athena, you may obtain a 75% discount off the list price if you meet certain income guidelines. For more information, see call (800) 394-4493 and ask to speak with a Reimbursement Services Representative.

03/18/2014

02/21/2014

To support our commitment to research, MDF awards fellowship grants to postdoctoral researchers as part of our annual Fund-A-Fellow (FAF) program. We recently caught up with one of our current grant recipients, Dr. Nicholas Johnson, Assistant Professor of Neurology at the University of Utah.

Dr. Johnson was inspired to focus his practice and research on myotonic dystrophy after working for five years at the University of Rochester with Dr. Chad Heatwole, Dr. Richard Moxley, Dr. Charles Thornton and a number of other clinicians and researchers leading the charge to find new treatments and cure for DM. He opened his practice at the University of Utah in July of 2013 and is excited to be able to treat the large DM population in Utah and surrounding states.

“There is an excellent neurology department at the University of Utah,” Dr. Johnson says, “but previously no one was focused specifically on researching DM. Being here gives me the opportunity not only to provide ongoing treatment to those individuals, but to include many of them in our research studies as well, which is exciting.”

We spoke with Dr. Johnson about his current FAF research.

MDF: First, tell us about the research you’ve been doing as a result of receiving the FAF grant.

NJ: “Sure. Once I received the FAFA grant, I began a project in March 2012 to develop a tool that can be used in a clinic or in research studies to measure how myotonic dystrophy impacts the quality of life of a child with congenital or childhood-onset DM. 

“The tool is called Congenital and Childhood Myotonic Dystrophy Health Index or CCMDHI. It’s a survey-based tool that collects data about quality of life from birth to age 18. Until now, there’s been very little data about how DM progresses from birth to adulthood, but that information is necessary for clinical trials to move forward.”

MDF: Can you tell us about the survey and what you’ve discovered in the two years that you’ve been conducting research? 

NJ: “We interviewed 32 children and 12 parents and created the survey with their direct quotes so we could compare how their symptoms might impact the larger DM population’s quality of life. The survey was then sent out via the Myotonic Dystrophy Family Registry, the National Registry for DM and FSHD at Rochester, and the Canadian Neuromuscular Disease Registry, as well as via Dr. Anne-Berit Ekstrom of Sweden, who takes care of a large population of Swedish patients with congenital or childhood DM.

“One of the salient discoveries was that there was more than expected cardiac issues reported in children when we asked parents about comorbidities. Another interesting result was that 20-30% reported ADHD or autism symptoms.

“Of children over 18 years old, 86% were unemployed, which is pretty significant and tells us that there are a lot of ongoing issues and we need to emphasize social support when we take care of these patients.  Communication problems are a huge issue. Reports of fatigue and difficulty with mobility were also reported.

“Importantly, reported symptoms seemed to vary between birth and age 18 and over. Issues for those with young children were very different from those with older teenage children. And all children were very different from the experience of adult onset DM. Parents reported significantly more communication problems, as well as emotional and social issues. On the upside, there were less myotonia and pain symptoms in the children.”

MDF: What happens next?

NJ: “Now that we have a preliminary instrument, we’re finishing testing and will be moving on to our next study. I’ll be working with a research team here at the University of Utah on a study called ‘Health Endpoints and Longitudinal Progression in Congenital Myotonic Dystrophy’ or HELP CDM.

“This study, which is funded by MDA, is expected to start in January 2014 and will validate CCMDHI while helping find other endpoints that will be important in clinical trials.

“During the study, children from birth to 13 years old will come in for a variety of testing, including strength and functional testing, speech and swallow testing, neuropsychological testing, and respiratory and cardiac testing. Sixty children with congenital DM, who are currently being treated here at the University of Utah and also at and University of Western Ontario, will be measured. Ultimately, we hope this will allow us to transition to successful trials and therapies for the pediatric population.

“Separately, we’ve partnered with MDF to send out a survey via the Myotonic Dystrophy Family Registry to see how women with DM are affected during pregnancy and whether symptoms improve or worsen. That survey will be going out soon. Previously, researchers have looked at complications that can occur during pregnancy but not how quality of life is impacted as a result.”

MDF: You’ve mentioned the national DM registries a few times. Can you speak to why it’s important to join these registries?

NJ: “The Myotonic Dystrophy Family Registry established by MDF and the National Registry for Myotonic Dystrophy at the University of Rochester have been instrumental in recruiting patients for our upcoming HELP CDM study. I mentioned that we’re also using these registries to conduct a number of surveys that will provide us with data we need to keep research moving forward. I encourage everyone to sign up, if they haven’t already. It really does make a difference.”

12/18/2013

Dr. Danielle Sheypuk, a licensed psychologist in New York, NY, was the presenter for our most recent webinar—the last for 2013— titled “Coping with Depression Associated with Having a Chronic Health Condition.” Dr. Sheypuk not only share information about the different types of depression but also discussed when those concerns should be escalated.

A variety of options were suggested for coping with depression, including:

• Working with a therapist
• Meditation
• Staying active, both physically and mentally
• Medication
• Socializing
• Practicing a process of exploration, acceptance and integration

Dr. Sheypuk noted that the process of exploration, acceptance and integration may involve skills-oriented training, such as dialectical behavioral therapy (DBT). One of the goals of DBT is the acceptance of one’s situation, finding renewed meaning in life, and integrating chronic illness into daily living.

Additionally, Dr. Sheypuk, who is an expert in the area of dating and relationships, suggested maintaining intimacy in one’s life through dating and romance.