In 2016, MDF’s Warmline received many phone calls from MDF community members who struggled to complete the application process for federal and state disability benefits, and who needed guidance on how to navigate the complex application process.

To help meet the needs of MDF families who are applying for U.S. disability benefits, MDF is releasing our newest community resource, "Applying for Social Security Disability Benefits", a new toolkit created to help individuals and families understand the process of applying for Social Security Administration (SSA) disability benefits.

The new toolkit was designed to assist individuals affected by myotonic dystrophy in navigating the application process for Social Security Disability Insurance (SSDI) benefits and Supplemental Security Income (SSI) benefits. The Social Security Administration (SSA) oversees both the SSDI and SSI benefit programs, and is the largest of several federal agencies that provide assistance to people with disabilities.

"Many members of the myotonic dystrophy community have indicated that they found the disability claims process to be confusing and tedious, so we prepared the toolkit to make the process much easier for the MDF community to navigate," said Paul Formaker, Program Director at MDF.

The "Applying for Social Security Disability Benefits", is available online, and print versions of the resource are also available by request via email or phone 415-800-7777. 

The myotonic dystrophy (DM) community has a strong champion in singer-songwriter Eric Hutchinson. As part of his long-time efforts to support Care and a Cure for myotonic dystrophy, Eric is offering one-of-a-kind fan activities and memorabilia in a new pledge campaign, and a portion of the proceeds will be donated to MDF. Eric is offering private concerts for you and your guests as part of the pledge campaign, a deluxe edition of his album Easy Street, a signed and personalized acoustic guitar, framed lyrics and the opportunity to have a private tour of New York City with him, among other items. The pledge campaign ends on December 31, 2016.

"I’m thrilled to announce the Deluxe Edition of my latest album, Easy Street!" said Eric. "I recently learned about PledgeMusic.com and thought it sounded like a fantastic way to share some of my time, new music and some special memorabilia with all of you. Plus, for the first time ever, ‘Easy Street’ is available on VINYL, the first time ANY of my albums has been on wax. I’ve spent a lot of 2016 educating people about myotonic dystrophy, a condition that has affected my dad and my family for a long time. Part of the proceeds from this PledgeMusic campaign will go to support MDF and myotonic dystrophy research.

"I know firsthand what living with myotonic dystrophy looks like for a loved one and his or her caregivers. I'm committed to helping to find care and a cure for DM and I hope you'll join me. I want to thank MDF for helping my family better understand myotonic dystrophy and letting us know that we’re not alone in living with this disease. I’m donating to MDF because it’s important to provide resources and support to families, and accelerate efforts to find a therapy."

Eric’s commitment to support the DM community is driven by his own personal connection to the disease: His father has DM, and for years Eric lived with fear and uncertainty about his own status. Eric wrote about his family connection to myotonic dystrophy this year in a heartfelt personal essay.

The MDF community is an amazing network of volunteers and advocates who inspire us all with the work they do to advance Care and a Cure for DM. Each year at the MDF Annual Conference we honor those who are doing outstanding work with Community Leadership Awards.

Congratulations and an enormous “Thank you!” to this year’s winners!

Advocacy Champion Award Winner

Carolyn Valek: community member with the most outstanding contribution to promoting awareness of DM this year

Carolyn Valek is one of MDF’s original Phone Buddies. She uses her experience as a patient advocate to dispense critical information to those in need. Her warm personality and deep concern for the community help newcomers quickly feel at home.

Carolyn runs the MDF Ohio support group and is an integral part of our newly launched Virtual Caregivers Support Group. She is one of our most devoted advocates, calling representatives on Rare Disease Day, writing letters to Congress to support the Orphan Drug Act, and attending MDF Hill Days in Washington, DC.

Congratulations and thank you Carolyn!

Team MDF Volunteer Award Winner

Loraine Dressler: community member with the most outstanding contribution to ensuring that the people in the best position to help have the knowledge they need to make a difference

Loraine Dressler’s dedication to supporting the DM community and her glowing positivity make her an inspiration to others. Loraine runs MDF’s Orange County support group and will also be participating in MDF’s Virtual Caregivers Support Group.

She takes part in our Grandparents’ Day awareness and fundraising campaign and is a long-time advocate who has met with members of Congress to advocate for DM funding and has provided testimony on the impact DM has had on her family to the Social Security Administration.

Congratulations Loraine! You are wonderful!

Humanitarian Award Winners

Taylor and Eric Jensen: community members with the most outstanding contribution to amassing resources for Care and a Cure

Taylor and Eric Jensen are a formidable grassroots fundraising team. They have turned their annual friends and family crawfish boil into a much anticipated and highly successful community celebration to support Care and a Cure. “Pinching Tails for a Cure,” has raised more than $110,000 since it began in 2013.

The Jensens also do all they can to help raise visibility for DM. They share their family’s story with reporters, participate in MDF awareness campaigns and speak at key events like the Ionis Pharmaceuticals Rare Disease Day employee event to help educate the world about DM.

Congratulations Taylor and Eric! We truly appreciate all you do!

"We will not forget your faces or your stories. Please know that all of your efforts will make a contribution to making [the regulatory review] process go smoother when a new treatment comes to the FDA to be reviewed."

- Dr. Larry Bauer, regulatory scientist, FDA

Optimizing the Review & Approval Process for DM Therapies

As many of our community members know, MDF held the first myotonic dystrophy (DM) Patient-Focused Drug Development (PFDD) meeting with key senior leaders from the Food and Drug Administration (FDA) as part of the 2016 MDF Annual Conference. We designed the meeting to build on the work MDF has been conducting with the FDA to define and optimize the regulatory pathway for potential DM therapies.

The DM PFDD Meeting – Why Do It?

The DM PFDD meeting, which was the first Externally-Led PFDD Meeting sanctioned by the FDA as well as the first PFDD meeting focused on DM, was conceived to follow on these earlier meetings, and particularly the full-day workshop in 2015, by moving from reports and discussion from regulators, academic researchers and industry professionals to insights and information provided directly by people living with DM and their caregivers. Decision-makers are increasingly realizing that the voice of the patient is a critical element in understanding how to develop and approve therapies that provide clinically-meaningful benefit to those living with a particular disease. Without patient insights, the FDA’s ability to assess the benefits and risks of a particular therapy, and its ability to provide real benefit to patients, is significantly impaired.

Laying the Groundwork – Earlier DM FDA Meetings

Earlier MDF meetings in 2014 and 2015 focused on the status of biomarker and endpoint development, insights and challenges with regard to DM clinical trial design and other key regulatory questions. The full day regulatory workshop MDF hosted in September 2015 included presentations from leading DM clinicians and researchers, and FDA representatives in divisions and offices that impact the regulatory pathway of DM therapies, including the Study Endpoints Team, the Office of New Drugs, the Office of Drug Evaluation 1 - Division of Neurology Products, which will be in charge of the actual review of potential DM therapies, and a number of other functions in the Center for Drug Evaluation and Research (CDER) at FDA.

The Largest PFDD Meeting Ever

Well over 200 community members, industry professionals, academic researchers and FDA representatives attended the meeting live and via the live stream MDF provided. FDA leadership including Dr. Janet Woodcock, who oversees all drug evaluation and research at FDA as the Director of CDER; Dr. William Dunn, who is the Director of the Office of Drug Evaluation 1 – Division of Neurology Products, the division that will review all DM therapies; Dr. Jonathan Goldsmith, Associate Director of the Rare Diseases Program, Office of New Drugs, CDER/FDA; Dr. Larry Bauer, a regulatory scientist in the Rare Diseases Program; and a number of additional representatives from the Office of Health and Constituent Affairs, the Office of Translational Sciences, the Study Endpoints team, and others also attended.

DM PFDD Meeting – Engaging the Audience

MDF held the DM PFDD meeting on Thursday, September 15, 2016 from 1-5 PM ET in a conference hotel located near the FDA campus. James Valentine, a former FDA professional who helped launch the PFDD process at FDA and who now works in private practice advising industry and others in the therapy development arena, facilitated. The meeting began with a review of disease manifestations and a clinical overview from Dr. Charles Thornton of the University of Rochester. We then moved to audience polling to understand the demographics of those attending the meeting, either live in the conference room or via live stream.

Attendees provided information on their diagnosis (DM1, DM2, CDM), whether they were a patient or caregiver, when they were diagnosed, first experienced DM symptoms, their age range, etc. MDF has no information on who the specific attendees were and how they voted; however the demographic information allows us to tie specific polling responses to the demographic particulars of participants - for instance patients versus caregivers, DM1 versus DM2 respondents and much more. Only patients and caregivers were allowed to vote during the polling sessions; academic, industry and federal agency attendees were not.

All polling results displayed immediately on the screen at the close of polling for each question, so that attendees in the room and participating remotely could see how the full audience was voting, and how their answers and experiences aligned with others.

Living with DM – What the FDA Wants to Know

The first panel presentation, entitled Living with DM, took attendees to the heart of the meeting agenda. This session began with remarks from four panelists selected by MDF to represent key elements of the DM community, including patients with DM1 and DM2, caregivers, individuals with congenital or childhood-onset DM, etc.

The Living with DM panel questions were:

• What 1-3 symptoms of DM have the most significant impact on your life?
• How do they affect your life on a typical day? On your worst day?
• Are there specific activities that are important to you that you can no longer do or do as well because of your condition?
• How have your symptoms changes over time?

MDF panelists for panel one included Glen Wiggans, Athens, GA; Judy Marks, Raleigh, NC; Lee Baker, Roanoke, VA; and Sarah Clarke, New York, NY. Each panelist gave five minutes of prepared remarks responding directly to the questions posed to the Living with DM panel, providing personal stories and examples that painted compelling and vivid pictures of life with DM1, DM2 and the experience of caregiving for family members who live with the disease. Their stories were factual, detailed, moving and sometimes funny, and added immeasurably to the perspective and understanding of those in the room who were there to learn.

Panel One Audience Input

Attendees in the room and participating via live stream also responded to the panel one questions via live and remote polling, and via moderated audience discussion. The audience polling and moderated discussion provided additional voices and perspectives to the FDA and enabled the facilitator to probe more deeply around topics highlighted as particularly significant by the polling responses.

Dr. Janet Woodcock, MD, the head of research and drug evaluation at FDA and a strong proponent of including the patient voice in drug development and evaluation, addressed attendees, congratulating MDF on hosting the first Externally-Led PFDD meeting and outlining additional opportunities for productive patient advocacy engagement in the regulatory environment.

More Community Insights – Challenges of DM, a Short Film

A picture (or short film) is often worth a thousand words, so MDF screened Challenges of DM, a short film we created specifically for the FDA as an educational tool. The film included short interviews with DM community members around the country who do not attend MDF events, and featured voices and experiences we felt were critical to creating a holistic picture of the DM disease experience.

Panel Two – Current and Future Treatments

Four new panelists presented on strategies and interventions currently used in their families to manage disease symptoms, how effective or ineffective these are, drawbacks and side effects, and what they would most like to see from future therapies.

Panel Two questions included:

• What current treatments or therapies do you use for symptom management?
• How well are these therapies or treatments working?
• What are the downsides, if any, to these treatments or therapies?
• What do you want from an ideal treatment?

Panelists included Pat Dinsmore, WA, DC; Suzette Ison, Morristown, IN; Joachim Boekelmann, Princeton, NJ; and Tom McPeek, Chillicothe, OH. Their presentations highlighted the significant lack of effective treatments and interventions available to people living with DM and the importance of finding and approving effective therapies soon. Audience members responded to the panel two questions during the polling session and moderated discussion, rounding out DM community perspectives regarding disease management strategies and community hopes regarding eventual therapies.

FDA Feedback – Well Done

Dr. Jonathan Goldsmith, MD, who is Associate Director of the Rare Diseases Program in the Office of New Drugs, CDER, FDA, wrapped up the meeting by reflecting on what he, as an FDA participant and listener, had heard from the panelists and attendees. He touched on the very real need that exists for effective therapies, and the profound and ongoing struggles families with DM live with every day. Dr. Goldsmith demonstrated, through his summary remarks, that DM is understood to be a real and specific disease for FDA attendees, and not just "muscular dystrophy".

Perhaps equally compelling, MDF received an email from Dr. Larry Bauer the next day, in which he congratulated MDF on the quality and scope of the DM PFDD meeting, stating:

"Please know that all of the FDA attendees were enlightened, deeply moved and educated about the realities of living with myotonic dystrophy. We will not forget your faces or your stories. The meeting also made it extremely clear how much a treatment is needed for DM. Please know that all of your efforts will make a contribution to making that process go smoother when a new treatment comes to the FDA to be reviewed."

Our Thanks to You

We at MDF would like to thank all our community members who made time to attend the meeting, either in person or via live stream, and participate in the polling that created specific feedback for the FDA. We are incredibly grateful to the panelists who spent significant time writing and editing their remarks, participating in practice sessions and helping represent the DM community to the FDA.

There Is Still Time to Share Your Thoughts

MDF is currently assessing the polling results and analyzing the responses received against the demographic information provided, to understand better how, for instance, DM1 versus DM2 patients responded to key questions, how caregiver input differed from patient input, any interesting regional differences, etc. We will create a Voice of the Patient Report this fall, which we will deliver to the FDA for use in future drug review processes. The Voice of the Patient Report will be critical content the Neurology Review division will take into account when assessing the benefits and risks of specific drugs, and whether they will provide therapeutic benefits that are meaningful to patients.If you were unable to participate via live stream or in the meeting on September 15th, you can still provide answers to the questions posed to panels one and two. MDF will accept emailed or telephone responses to the questions until 5 PM PT Saturday, October 15th, 30 days after the DM PFDD meeting.

Questions?

Contact MDF via email or at 415-800-7777.

The Jensen family has a long tradition of hosting an authentic Louisiana crawfish boil with live music for their family and friends in San Diego. The Crawfish Boil became a fundraiser in 2012 when Taylor Jensen and her young son, River, were diagnosed with myotonic dystrophy type 1 (DM1). The Jensen's learned first-hand how complex DM is and how it impacts an entire family. After struggling with the initial impact of the diagnosis, Taylor and Eric evolved the family tradition into a fundraiser to support Care and a Cure.

The Fundraiser has two ultimate goals: to raise awarness of the most common form of muscular dystrophy known as myotonic dystophy (DM); and to to raise funds to continue the research that will enable treatments and an eventual cure. This year marks the first time people living with DM are receiving a potential therapy. The first DM clinical trial began this year, evaluating a medication that targets not just disease symptoms but the genetic mutation that causes the disease.

This year the Jensen Family had their 5th Annual Crawfish Boil Fundraiser ("Pinching Tails for a Cure") hosted at the San Diego Harley Davidson Dealership. Thanks to the sponsors and donors, the Crawfish Boil was a success, raising over $30,000 - bringing that to a total of $110,000 over the last five years!

You can read more about their personal journey with DM in this letter from the Jensen family.

Are you interested in hosting a fundraiser for Care and a Cure? MDF is here to help.

The annual Biotechnology Innovation Organization's (BIO) International Convention was held in San Francisco, CA earlier this summer. BIO represents more than 1,100 biotechnology companies and other organizations, and the annual Convention usually attracts more than 15,000 attendees. BIO is the trade organization that represents biotechnology and pharmaceutical companies, academic institutions, and biotechnology centers and organizations dedicated to innovation in biotechnology. The annual BIO Convention provides unprecedented partnering opportunities, and thus is a critically important forum for MDF to both learn from and educate potential partners in drug development for myotonic dystrophy.

The BIO Convention provided MDF with myriad opportunities to meet with industry partners that are already working in drug development for DM, have potential interest in DM, or are developing technology that MDF believes could be used to create potential therapies for DM patients. 

MDF staff and board member Dr. Woodie Kessel met with senior representatives of 11 different biotechnology companies at BIO, who are either existing partners with drugs in preclinical or clinical development for DM (including AMO Pharma and Amorchem/Roche), or currently in early stage development efforts. 

Staff also used the face-to-face meetings to evaluate the applicability of technologies such as gene therapy via companies experienced in cell line development as potential DM treatments. MDF used the meetings to describe the comprehensive infrastructure, data collection, funding and other efforts put in place by DM stakeholders (including MDF) to lower the risks to new DM drug development, to help ensure that the DM drug development pipeline continues to expand.

Drug discovery and development programs are inherently high-risk investments for pharmaceutical and biotechnology companies. Engagement and recruitment of new companies to work on DM, as well as continuing efforts to foster companies already working in the area, are critically important goals for MDF. 

As many MDF community members know, MDF has been working with a group of expert clinicians from across Western Europe, the U.K, Canada and the U.S. for the past year to develop consensus-based clinical care recommendations for myotonic dystrophy. We first talked about this project as part of a larger story about our three year, multi-million dollar drug development and care expansion effort. We have made excellent progress since we first mentioned this program in May 2015, and we are pleased to bring you an update on this unique initiative.

What Are Standards of Care and Why Are They Important?

Standards of care are critically important to help ensure that all patients with a particular disease receive appropriate and beneficial clinical care. They are typically based on rigorous data captured through large, anonymous research studies, and are usually developed and issued by the leading professional organization for that particular disease. In the case of myotonic dystrophy, that organization in the U.S. is the American Academy of Neurology (AAN). AAN has been working on an Evidence-Based Guideline for myotonic dystrophy for over five years, and hopes to publish it in 2017.

Clinical care guidelines will be particularly meaningful for the DM community because, as our community knows well, many doctors who do not see DM patients regularly are not aware of the range and variation in symptoms that are part of living with myotonic dystrophy. They do not necessarily know what testing, exams and follow up are appropriate for people living with DM, and they may miss important impacts to some organ systems. Often it is the DM patient who educates the physician about the disease and the care that is needed. MDF is committed to helping ensure that care recommendations are available and delivered to the clinical professionals who treat DM patients.

The DM Guideline, when it comes out, will be published and disseminated to neurologists in the U.S. It will not address most of the organ systems and symptoms of importance to myotonic dystrophy patients because the studies needed to gather the evidence required to establish a guideline have not been conducted.

MDF is working with the AAN to support the eventual dissemination and publication of the DM Evidence-Based Guideline when it is ready, and most of the members of our Scientific Advisory Committee are part of the team involved in its creation. Dr. Tetsuo Ashizawa, formerly the head of neurology at the The University of Florida and now leading neurology research at Houston Methodist, is the lead clinician on The DM Guideline.

What are Care Considerations and How Are They Different?

MDF has had a number of meetings with the U.S. Centers for Disease Control (CDC) and the AAN to understand what the newest publication date is for the evidence-based guideline, and how robust the final publication will be. The AAN and CDC have heavily encouraged MDF to pursue the development of consensus-based care recommendations in order to ensure that comprehensive care recommendations are available to all clinicians treating DM patients because a comprehensive evidence-based guideline is many years away.

Consensus-driven care recommendations are clinical care recommendations developed by experts in the appropriate disease field, who work through a formal consensus-development process to come to agreement on how patients across many countries and continents should be treated to help patients maintain health and improve their quality of life.

The Myotonic Dystrophy Care Considerations

In the case of the DM Care Considerations, MDF has assembled a truly world-class team of 60 expert clinicians from across the globe, in fields as diverse as cardiology, pulmonology, occupational therapy, pain and family planning, to work through a consensus-building process to create the first-ever clinical care recommendations for adults with myotonic dystrophy type 1. Care Considerations for congenital myotonic dystrophy and myotonic dystrophy type 2 will follow very shortly. Both the CDC and AAN are partners on the MDF Care Considerations project and are providing significant support to the project. MDF has also teamed up with Treat-NMD, Muscular Dystrophy UK and organizations in Canada and Western Europe to ensure that these guidelines are appropriate and targeted to patients in many different countries and care situations.

What’s Been Accomplished?

The project formally kicked off at the 2015 MDF Annual Conference, where MDF held a meeting with the international working group to provide an overview of the project scope, the consensus-development methodology, and study area assignments. Eight multi-system study areas were established, with committee chairs and working groups for each. Click here to see the full international list of Care Considerations study areas and Working Group participants.

MDF created and circulated to the working group a draft list of care recommendations developed from the MDF Toolkit and a short list of key published research. The expert clinicians then met via conference call and email, reviewing and editing the recommendations for their study areas over the course of the winter. MDF assembled an updated draft of care considerations with the edits included, and then brought all available working group members to Miami to discuss the revised document and work toward final recommendations and consensus. The meeting was a significant success, and MDF is now assembling the final draft document to circulate for a last round of reviews to the working group.

What’s Next?

The next steps for the DM Care Considerations project will be extensive and will involve multiple international partner organizations. Once the working group has agreed on the final list of care recommendations, MDF will develop executive summary and full versions of the document, as well as a draft publication for submission to a neurology journal. The full version will be submitted to professional associations of clinical professionals for open comment and to accreditation organizations in Western Europe, the U.K., Canada and the U.S. (AAN) to begin the final approval and dissemination process. Additional international organizations will be significant partners in distributing the final recommendations to care providers internationally.

MDF will also pursue an insurance policy document to help convince insurance companies in the U.S. to provide reimbursement for these care recommendations, and MDF has developed a draft update policy to ensure that these recommendations stay current. Finally, MDF will work with the working group and our international partners to develop and implement an assessment program to measure whether these recommendations are being used and are improving care for DM patients.

We plan to have final approved documents ready by the end of 2016. As always, MDF will keep you posted on this and our other research and care projects as we move forward. Questions? Contact MDF via email or phone at 415-800-7777.

Since its discovery almost 25 years ago, researchers have been working to try to understand the DNA mutation causing myotonic dystrophy type 1 (DM1).

The mutation is known by many names, including “CTG repeat,” “triplet repeat,” “trinucleotide repeat,” “expansion mutation” and many more. Over the years researchers have determined that the mutation is unstable, and most often grows larger in size. Not only does the repeat usually get larger each time it is passed on to children, it can also get larger inside an individual person. 

For example, a common blood test for DM1 taken from the same person several times over many years reveals that the repeat grows slowly over time. It is important to note that a repeat size reported on a genetic test most often reflects an average size, or the most commonly found size of the repeat, it does not represent the size found in every single blood cell. 

Furthermore, the repeat size in the muscles of an individual with DM1 will often be many times bigger than the repeat size found in their blood, making the study of DM1 repeat size a very complicated research field. 

Researchers have puzzled over why the repeat is so unstable, and what drives the repeat to expand so much in some types of cells, and in some people more than others. In order to understand this better, researchers from the University of Costa Rica and the University of Glasgow teamed up to examine the DNA from 199 individuals with DM1 in order to determine what might be driving the repeat to grow. 

This team had previously developed a way to mathematically predict the original repeat size found in an embryo at the time of fertilization, and determined that this predicted repeat size could more accurately predict the age someone with DM1 would first experience any symptoms. In fact, this predicted repeat size was calculated to be responsible for 89% of the variability seen in blood over time. However the remaining forces driving repeat instability were unknown. 

In this recent publication, the same team explored whether there were other genetic factors aside from the repeat that might be inherited, and driving instability. They found that one variation in the genome, inside a gene called MSH3, was strongly connected to an increased amount of instability. 

This gene has previously been connected to the instability of DNA repeats, however this is the first time a naturally occurring variation has been connected to driving instability in people with DM1. Researchers call this variation a “modifier,” because it modifies how the DNA repeat behaves over time. 

Since larger DNA repeats have been previously associated with more severe symptoms, it is possible that future research might show that symptoms can be worse or better depending on which of the two variations of the MSH3 gene you inherit from each of your parents.  

However, that type of study would likely require many more patient samples than this preliminary study of 199 individuals. Interestingly, a study on cancer risk found that this same variation was linked with an altered predisposition to cancer, but the variant that had negative consequences when it came to cancer risk was the variant that saw less instability in DM1. Therefore, this variant can have both positive and negative consequences in humans.

Reference:

A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.
Morales F, Vasquez M, Santamaria C, Cuenca P, Monckton DG.
DNA Repair (Amst). 2016 Mar 8.

MDF is pleased to announce that Dr. Melissa (“Missy”) Dixon, a Research Associate in the Deptartment of Neurology at the University of Utah, has been awarded a 2016-2017 postdoctoral fellowship.

Dr. Dixon’s research proposal is titled “Evaluation of Functional Connectivity as a Brain Biomarker in Congenital Myotonic Dystrophy.” In this study, she and her colleagues will use magnetic resonance imaging (MRI) to evaluate connectivity networks in the brains of children with congenital-onset myotonic dystrophy (CDM) to see if they differ from those of children without CDM, whether they change over a one-year time period, and whether the MRI results correlate with data from neuropsychological testing.

Dr. Dixon has an extensive background in clinical psychology, neuropsychological testing and clinical trial coordination. She received her doctorate in counseling psychology from the University of Utah in December 2015. We recently talked with Dr. Dixon to learn more.

MDF: There was a time when most children with CDM didn’t survive very long. Do they have a better prognosis now?

MD: Oh, absolutely. I would say that kids with this disorder have a better prognosis than they did a decade ago. We now know that respiratory and feeding problems can be life-threatening, and we’re better equipped to work with those issues from the start.

MDF: What is known so far about the neuropsychology and the brain abnormalities in children with congenital-onset myotonic dystrophy?

MD: Networks in the brain are kind of like a highway system. You can get from Illinois to Colorado by taking Interstate 80, but if there’s a block in that road or a piece of the road that’s missing, you have to take a different route to go around it. 

I don’t know if there are fewer “interstates” in the brains of children with CDM compared to those of children without CDM, but it may be that they’re using more roundabout pathways for getting from one place to another. I think the networks are different [from those in unaffected children.]  

People have used resting-state functional MRI [fMRI] during the resting state [without an attentional focus] to look at brain connectivity in kids who have autism, and they’ve found that it’s sensitive enough to show that there are differences in their connectivity networks. 

Earlier DM studies relied on structural imaging techniques. These can demonstrate a wide range of changes, but they’re not well correlated with clinical outcomes, such as IQ.

We think that by using fMRI we’ll be able to look at connectivity differences in these brain networks and see if they change over time in kids with CDM. 

MDF: Will this study be helpful in telling parents what to expect as their child matures?

MD: We’re hoping to be able to demonstrate changes over time by looking at blood flow in the brain using resting-state fMRI, at baseline and then at a year from baseline.

We’ll be tracking neuropsychological measures, such as executive function and IQ assessment. We’ll also look at adaptive behavior, at how a child is functioning, through a questionnaire that a parent or caregiver will fill out.  At the completion of the study, we would hope to tell parents where a child may have the most learning difficulty, and design interventions to approach those learning difficulties.  

MDF: If you do see abnormalities in connectivity in the brain, what are the possible implications?

MD: We know that cognition is impacted in CDM, but there is not a very sensitive way to see how this changes during the course of a short period of time, like during a drug trial. This technique could become an endpoint for a clinical trial to test the effect of a potential drug or therapy.

MDF: Is it possible that something like, say, DMPKRx, which is being developed by Ionis Pharmaceuticals, could have an effect on the brain, if it could be made to cross the blood-brain barrier?

MD: If not that particular therapeutic, then perhaps another, could potentially slow or halt the progression of the brain changes in this disease as we learn more about them.

MDF: Can you say more about the fMRI study?

MD: We’ll be enrolling 20 participants with CDM, ages 7 to 14, and we already have a control group for comparison. We’re not recruiting yet for the fMRI study; we’re still at the IRB [institutional review board] stage, applying for study approval. We hope to start recruiting in June 2016, and we’ll be posting that on the MDF site when we do. [Studies are listed at the MDF Study and Trial Resource Center under the Current Studies and Trials tab.]

We do, however, have an ongoing study of the natural history of CDM here at the University of Utah, and we hope to recruit some participants for the fMRI study from that group. [The natural history study, which is open, is Health Endpoints and Longitudinal Progression in Congenital Myotonic Dystrophy. Read more about it at the MDF Study and Trial Resource Center under Current Studies and Trials.]

We’ve done neuropsychological testing with the children in the natural history study. The children are all different, and that’s what makes CDM so interesting. The cognitive piece is fascinating. That profile for them is definitely varied, and I think that some of the measures that we’ve been using are just not sensitive enough to understand what’s going on.

I chose 7-year-olds as the lower cut-off age, because they have to stay in the fMRI scanner for 20 to 30 minutes. That can be difficult or scary for any child, and children with CDM sometimes have sensory issues. They’ll have something that’s like a fish tank for them to watch during the scan. It’s not like a movie, where they’d be actively thinking about things, but they’ll be looking at something.

MDF: You have a broad background in clinical psychology. What led you to study children with myotonic dystrophy?

MD: In 2013, when [neuromuscular disease specialist] Dr. Nicholas Johnson came here from the University of Rochester, I became interested in people who have myotonic dystrophy, particularly congenital myotonic dystrophy. I’m interested in understanding the neuropsychological differences in this population. There isn’t a whole lot of known information about congenital myotonic dystrophy and neuropsychological function.

MDF: Did you know that another MDF research fellow, Dr. Ian DeVolder, is doing a study of fMRI in adults with type 1 DM?

MD: Yes, I saw that. That was great to see that someone is doing something very similar in adults. I’m sure our paths will cross as we move forward in our careers. Hopefully, both of our efforts will better define the neuropsychological dysfunction throughout the life spectrum.