Myotonic Dystrophy Anesthesia Guidelines

Please know that the use of anesthesia raises special risks to those living with myotonic dystrophy (DM), as the disease results in heightened sensitivity to sedatives and analgesics. Pay particular attention to the serious complications that can arise in the post-anesthesia period, when risk of aspiration and other complications increase. 

MDF has published two versions of its Anesthesia Guidelines:

• A one-page summary of the anesthesia guidelines to share with your clinician and anesthesiologist.
• The complete "Practical Suggestions for the Anesthetic Management of a Myotonic Dystrophy Patient".

Download an electronic copy of the latest versions of both documents on the Toolkits & Publications page.

New to DM? Click here for more information.

Many MDF community members are aware of an important, multi-year MDF effort -- MDF 3.0: Accelerating Drug Development -- because we published an article on the launch of this initiative in early 2015.

As you may know, the goals of MDF 3.0 are to:

• Strengthen capacity and infrastructure in DM clinical care to drive more accurate clinical trial design, improve capacity to evaluate drug efficacy and advance understanding of disease course
• Deepen and strengthen the research and development bench to drive more myotonic dystrophy discoveries
• Expand the drug development pipeline with additional pharamceutical partners, additional translational research and more critical data
• Incentivize investment in myotonic dystrophy via key studies, data collection, industry partnerships and a targeted and immediate advocacy effort with federal agencies and legislators

Below is a first-year report on how elements of MDF 3.0 got launched and how we are doing to date.

1.   Expand the Fellowship Program

First launched in 2009, MDF's Fund-a-Fellow (FAF) program was designed to:

• Attract new investigators to the field of myotonic dystrophy (DM) research
• Increase interest and activity in the field of myotonic dystrophy research
• Expand knowledge and understanding of DM
• Increase the number of labs and academic programs engaged in or expanding their engagement in DM research

To date, MDF's FAF Program has funded seventeen postdoctoral research students, providing over $1,700,000 to DM research focused on enhancing the quality of life of people living with DM and advancing research focused on finding treatments and a cure for this disease.  

And for 2016, an unprecedented six new fellows have been funded, who are pursuing research projects ranging from understanding the cognitive effects of DM to making a mouse model of DM2.

2.  Conduct a Prevalence Study

A major objective of MDF 3.0 is to determine how common the DM1 and DM2 mutations are in the general population. Many have quoted the figure “1 in 8000” as the “prevalence” of myotonic dystrophy—that is, how many people may have the disease at any given time—but this number comes from studies done in other countries, and it also relies on diagnosed cases of DM. Given that the diagnostic odyssey can take as long as 14 years in myotonic dystrophy, it is likely that diagnosed cases represent the tip of the iceberg.  

An accurate understanding of the occurrence of DM in the population, both diagnosed and undiagnosed, is a fundamental building block for efforts to improve treatment resources and develop a cure for DM. In 2015 MDF released a “Request for Applications” to fund the first of a two-part project to understand how common these mutations are in the population.

In October, MDF announced that funding for the first phase of this project will go to Dr. Nicholas Johnson at the University of Utah. Dr. Johnson will focus on making sure that he can scale up his diagnostic testing method to process 50,000 or more total samples at a reasonable cost.  

In the next phase of the project, which will be announced in the spring of this year, MDF will invite investigators to submit their plans for screening a random sample of the population for mutations that cause DM1 and DM2. Results are expected in early 2017.

3.  Create access to tissue samples 

Early in 2015, MDF began hearing from members of industry that they were having difficulty obtaining biological samples, particularly cell lines, from people with DM that they could use to identify drugs that might be developed into therapies.

To help address this problem, MDF partnered with Orig3n, a new biotechnology start-up company that is specializing in creating cell lines from rare disease patients. Under a memorandum of understanding (MOU) between MDF and Orig3n, the company came to the 2015 MDF Annual Conference and drew blood from approximately 50 volunteers. The company intends to create cell lines over the next 12 months. The majority of Orig3n samples are from current Myotonic Dystrophy Family Registry members and can be tracked to their registry records anonymously through a unique identifier number, providing useful additional information about the cell line donors.   

MDF is working with Dr. John Day’s group at Stanford University and other investigators with biobanks to raise visibility and promote more community and researcher participation in them.

4.  Drive drug discovery through an assay development and screening project 

In June MDF issued a Request for Applications to help identify possible new drugs for myotonic dystrophy. This led to collaboration between academic investigators with in-depth DM knowledge and industry and industry/government entities with drug development experience and scale-up capabilities.

A panel of experts in drug screening and therapy development reviewed the proposals submitted and chose the team that will receive a $200,000 award over the next year. The successful applicants will be announced in the next issue of the DM Research News.

5.  Accelerate identification of appropriate DM biomarkers and clinical endpoints

Biomarkers and clinical endpoints are different ways of measuring changes that occur as a consequence of a disease, over the course of a disease or in response to an intervention.  A biomarker is typically evidence of a physiological change that has occurred, often detected in blood or tissue samples, that is relevant to the disease process. A clinical endpoint is some way of measuring how a patient “feels, functions or survives.”  

Biomarkers that provide early evidence that a drug is working are crucial for making drug development economically feasible. This is especially true for diseases that progress relatively slowly, like DM.

Biomarkers are also useful in creating better trials (by selecting people with DM who have specific characteristics for trials or making sure those characteristics are balanced in the different groups that make up the trial).  

MDF held a meeting in Fall 2014 to explore the status of biomarkers and endpoints for myotonic dystrophy, addressed biomarkers at the FDA regulatory workshop in the Fall of 2015 and will issue a Request for Applications in Spring 2016 to provide support for the development or refinement of biomarkers for myotonic dystrophy.  

In addition to the need for biomarkers, the need to identify an appropriate primary clinical outcome measure for new therapeutics is becoming an urgent priority as the DMPKx phase I/II clinical trial moves toward completion.   

The primary clinical endpoint is the test that will be used by the Food and Drug Administration to determine if an experimental treatment actually works. For example, a clinical endpoint could be the time it takes someone to get up from a chair and walk 30 feet, or it could be a person’s score on a survey about the severity of his or her symptoms. The scientific community has proposed various endpoints.  

In November 2015 MDF released a request for applications to support projects to develop new endpoints for myotonic dystrophy or to further refine endpoints already in development. Successful applicants must demonstrate how they will work closely with FDA staff to ensure that the work will be useful from a regulatory standpoint. Successful applicants will be announced in late Spring 2015.

6. Federal Advocacy

Regulatory Advocacy

As part of the three year 3.0 effort, MDF launched a significant advocacy effort targeting US congressional leadership, federal agencies involved in the drug review and approval process, agencies leading research investment and policy, and international bodies with impact and influence on the drug development and approval processes. 

MDF hosted the first-ever meeting of stakeholders involved in drug development to look at the regulatory pathway and better understand how potential DM therapies will be reviewed and assessed by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and others. More than 80 participants from academia, industry, the FDA and other federal agencies joined MDF in September 2015 to review progress toward the development of biomarkers and endpoints for DM clinical trials, the design of clinical trials, and to hear feedback and information from the FDA to help guide their drug development efforts. 

As a part of that meeting, MDF also contracted with Silicon Valley Research Group to conduct the first-ever benefit-risk study for myotonic dystrophy potential therapies, to introduce first-phase information on what therapy benefits are most important to DM patients and what risks patients would be wiling to accept for those benefits. The findings from this study were presented at the FDA workshop at the suggestion of the FDA. 

Because the patient perspective is becoming increasingly important in the overall drug development and approval process, this benefit-risk study will be followed with other MDF efforts to present the patient voice and perspective to the FDA and other regulatory and federal bodies in the months ahead.

The meeting helped industry get current thinking from the FDA, and was followed by a half-day workshop of just industry and academic participants to discuss what they heard, explore common areas of potential partnership or barriers to progress. MDF is working with a professional science writer to finalize a draft publication of the proceedings from the all-day workshop, and plans to submit it for publication in early 2016. 

Legislative Advocacy

In early 2015 MDF hired a public policy firm in WA, DC to help define and deliver a comprehensive strategy to drive Care and a Cure through 2017. A key recent effort involved crafting report language and direction that will be proposed for insertion into the 2016 US federal budget to influence research investment and other policy work that is important to the DM community. MDF also engaged the team to bring congressional leadership to the first-ever legislative briefing MDF held on Capitol Hill in conjunction with our 2015 MDF Annual Conference and Hill Day, and to develop the materials used to educate Congress about critical DM issues. MDF will continue this work in 2016 with outreach and education efforts with key congressional leaders and additional grassroots and grasstops advocacy work in partnership with the MDF community.

Federal Agency Advocacy

People living with DM often struggle with the application process for Social Security disability benefits. MDF investigated and then met with the Social Security Administration (SSA) to explain the issues we experience and how the SSA can improve the process and outcomes for people with DM. MDF staff, DM physician Dr. Ami Mankodi and DM community members (Larry and Hunter Lord, and Loraine Dressler) participated in the meeting.

MDF will build on this work with education programs for the 2,500 SSA staffers who review claims in the field, and will create a Toolkit for community members to make the application process easier.

MDF also attended a number of Muscular Dystrophy Coordinating Committee (MDCC) meetings, applied for a position on the MDCC coordinating committee, supplied several rounds of proposed edits to the current MD CARE Act Action Plan (which the MDCC oversees), and held partnership meetings with key federal agencies including the National Institute of Neuromuscular Disorders and Stroke (NINDS) and other National Institutes of Health (NIH) agencies that influence the advance of DM science and research funding.

Grassroots and Grasstops Advocacy

MDF built on its first ever grassroots advocacy efforts in 2014 with a second Hill Day, bringing more than 80 community members to Capitol Hill to educate legislators and their staff on issues important to the DM community.  This work will expand significantly in 2016 with one-on-one meetings with key policy makers.

In short, 2015 was a great kick-off year for MDF 3.0, and we look forward to more high-impact work in 2016. We will keep you apprised.

Questions?

Please contact MDF. We would love to hear from you.

While symptom themes such as inability to do activities, mobility limitations and weakness were the most common, fatigue was the symptom that had the greatest impact on patients' lives. This research will help focus developing treatment strategies on the most important issues reported by people with DM2.

These findings are similar to those from a previous study from the same authors that examined symptoms in DM1, where fatigue was also ranked as the most burdensome symptom but not the most common.

More on the study:

In this study, researchers interviewed and sent surveys to people across the USA with DM2, asking respondents to report what symptoms they were experiencing, and what impact those symptoms had on their daily living.

Symptoms were grouped into themes, and researchers found that the most commonly reported symptom themes were:

• Inability to do activities (94%)
• Limitations with mobility or walking (89%)
• Hip, thigh, or knee weakness (89%)
• Fatigue (89%)
• Myotonia (83%)
• Pain (80%)

When the themes were broken down into individual symptoms, the most commonly experienced symptoms included difficulties getting up from the floor, squatting, walking hills, rising from a seated position, and other issues stemming from leg weakness.  These symptoms were experienced by at least 97% of the respondents.

Aside from assessing symptoms, this study also gathered information on employment, age, duration of symptoms, and gender. This allowed the researchers to break down their DM2 respondents into groups to determine whether there were any subsets of the population that had a different experience with DM2 than others.

They found that the significant differences between subsets of the population came when patients were grouped by employment status. Unemployed respondents more commonly reported mobility or walking issues, problems with shoulders or arms, emotional issues, decreased satisfaction in social situations, and many other symptomatic themes.

The researchers believe that “employment status is highly dependent on a patient’s overall disease burden,” and also found that employed respondents had better satisfaction in social situations. While this study was not designed to determine cause and effect, the authors hypothesize that many symptoms of DM2 may make obtaining employment difficult or impossible. They further hypothesize that unemployment may also potentially lead to increased disease burden in DM2.

To read an abstract of this article, click here. 

MDF is pleased to welcome Dr. Kathie Bishop, Ph.D., to its Scientific Advisory Committee(SAC). Dr. Bishop, who joined the SAC in summer 2015, is a seasoned expert in neurological and neuromuscular research and drug development.

She received her Ph.D. in neurosciences from the University of Alberta (Canada) in 1997 and then completed a postdoctoral fellowship in molecular neurobiology at the Salk Institute in La Jolla, Calif.

From 2001 to 2009, Dr. Bishop was at Ceregene, a San Diego biotechnology company developing gene therapies for neurological disorders. At Ceregene, where she was Director of Research and Development, she worked on preclinical and clinical programs in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, retinal degenerations, and amyotrophic lateral sclerosis (ALS).

In 2009, Dr. Bishop moved to Ionis (formerly Isis) Pharmaceuticals in Carlsbad, Calif., a biotech company specializing in antisense oligonucleotide-based therapeutics. While at Ionis, she led programs within the neurology franchise, including leading development for programs for spinal muscular atrophy, amyotrophic lateral sclerosis, type 1 myotonic dystrophy (DM1), and other rare genetic neurological disorders. She left Ionis Pharmaceuticals in 2015, as Vice President of Clinical Development.

She is now Chief Scientific Officer at Tioga Pharmaceuticals, a San Diego biotechnology company developing treatments for chronic pruritus. We talked with Dr. Bishop in October 2015:

MDF: What prompted your decision to move from academia to industry?

KB: I’ve always been interested in genetic neurologic diseases. My original degree was in genetics, and my Ph.D. is in neuroscience. While at the Salk Institute for my postdoctoral fellowship, I worked on development of the brain and spinal cord and found I wanted to apply the science to drug discovery and development.

MDF: What kinds of drug development programs have you worked on?

KB: At Ceregene, we were developing gene therapies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ALS [amyotrophic lateral sclerosis].

When I moved to Ionis, my first program was developing antisense against SOD1 for ALS. We did a phase 1 clinical trial administering IONIS-SOD1Rx into the CSF [cerebrospinal fluid] in patients with the genetic form of ALS, and no safety issues were found. [See Miller et al., Lancet Neurology, May 2013.] At the time, we were concentrating on whether the CSF delivery of antisense drugs would be feasible and safe, which it was

I led the SMA [spinal muscular atrophy] program at Ionis from the preclinical stage through the phase 1 and phase 2 trials and up to trial design and initiation of phase 3 studies. IONIS-SMNRx acts on the SMN2 gene to change SMN2 splicing so that a functional protein is made. It acts right on the disease mechanism. This antisense [ASO] drug is the same chemistry as IONIS-SOD1Rx, but it doesn’t downregulate the SMN protein the way IONIS-SOD1Rx downregulates the SOD1 protein. The ASO doesn’t have a gap for an enzyme to bind that would downregulate the SMN RNA. It’s now in phase 3 studies in infants and in children with SMA.

I was also involved with developing IONIS-DMPKRx, an ASO against the DMPK RNA to treat type 1 myotonic dystrophy [DM1]. We completed a phase 1, single-dose study in healthy volunteers, and a multiple-dose study in adults with DM1 is ongoing. IONIS-DMPKRx destroys the DMPK RNA, which is thought to be the cause of DM1. It also affects the wild-type DMPK allele, but it may have a preference for the [abnormally expanded] DMPK RNA that’s stuck in the nucleus.

MDF: Do you see other therapeutic avenues for DM?

KB: Yes, absolutely. I think any one therapy, even one which acts on the genetic mechanism in DM, might not work perfectly in longstanding disease and might not work on all aspects of the disease or in all patients. We may need other compounds, such as muscle-enhancing drugs, to supplement it and be taken together with it. We will also need additional drugs that work on other aspects of DM, such as drugs that help stop degeneration in smooth muscle and heart, as well as CNS [central nervous system] drugs. Antisense drugs such as IONIS-DMPKRx do not penetrate into the CNS when given systemically, and particularly in the congenital and juvenile-onset forms of the disease, the CNS effects need treatment.

MDF: What do you see as the main challenges to drug development for DM and other rare disorders? For example, how can small companies meet the demands of patients for expanded access to compounds in development while pursuing full regulatory approval for these compounds?

KB: I think it’s the responsibility of people like me, who work in drug development, and of drug companies to communicate effectively about the development process and the risks involved to patients, their families, and their caregivers. We have to make it clear that experimental treatments could be harmful, and we have to be realistic and honest about the potential benefits. There is a lot of hope, but we also need to communicate better with the patient community about the drug development process.

That said, I would like to see the drug approval process be more efficient and go faster for diseases where the drug has a clear mechanism that acts directly on the underlying genetic cause of the disease. I think the FDA [U.S. Food and Drug Administration] is on board with this, but they aren’t going to come up with solutions. The drug developers have to do that.

MDF: What particular challenges do you see with drug development for DM?

KB: The clinical outcome measures used in this disease change very slowly, so you need long trials to measure decline. We need molecular markers, such as those reflecting splicing changes downstream of the mutant DMPK RNA that are linked to clinical changes. These are known as surrogate markers, and companies have to provide the data on these markers and clinical outcomes to the FDA.

MDF: What particular skills and insights will you bring to the MDF Scientific Advisory Committee?

KB: I plan to advise MDF on DM drug development and on incorporating science into drug development. I hope to help with encouraging and supporting new drug discovery and development programs for treatments for DM, advising on clinical trials, developing surrogate markers in DM, and having an effective working relationship with the FDA.

Generating "Benefit/Risk" Information for Drug Assessment

As part of our investment in the development of effective treatments for myotonic dystrophy, MDF is helping develop what is called "benefit/risk" information for regulatory agencies reviewing potential therapies. We need to better understand how people with DM weigh the benefits of new treatments against the risks these therapies might pose. To do this, MDF worked with Silicon Valley Research Group to conduct a survey that presented a series of hypothetical new treatments and asked that MDF community members choose the drug benefits that were most important, and what what they thought of potential side effects (some readers may recall having received an email solicitation for this survey over the summer). 

This type of analysis is called “Max-Diff Analysis” or sometimes “Best-Worst Scaling” and has been used in other benefit-risk studies and by the Food and Drug Administration (FDA) to develop "benefit/risk" information.  This method allows us to use robust statistics to determine, on average, what risks people living with myotonic dystrophy are or are not willing to accept for a given therapeutic benefit. The FDA and other international regulatory agencies are very interested in this information. 

A special thank you goes out to the 267 of MDF community members with DM1 and DM2 who met the entry criteria for the survey and soldiered through what may have felt like a lengthy and repetitive series of questions.  

What We Learned

The survey showed that reversing, stopping and slowing the progression of muscle weakness were the most preferred benefits, in that order. The side effects community members were most willing to tolerate overall for any therapy benefit were loss of appetite and a small increase in tiredness.  

People in the study also completed a short survey to rate the severity of their myotonic dystrophy.  Scores were grouped into mild, moderate and severe categories. For the majority of benefits, those with all levels of severity were similar in their willingness to tolerate side effects, except that those with more severe myotonic dystrophy were less willing to risk liver failure for any type of therapeutic benefit. Also, those with the highest severity rating for their myotonic dystrophy were more willing to tolerate an increase in tiredness if the drug could stop or reduce myotonia. The data reported here are based on the survey responses from those with DM1. The responses from those with DM2 are being analyzed now.

What's Next

These results were presented on September 17th at the MDF-sponsored all-day regulatory workshop on therapeutic development for myotonic dystrophy, which was attended by FDA staff, members of industry and the academic community. Next steps will likely include an in-depth follow-on study that looks at the benefit-risk preferences of caregivers and younger people with myotonic dystrophy. MDF is also investigating ways to collect “qualitative” data, such as stories and open-ended comments, regarding the benefit-risk preferences of those with myotonic dystrophy. Ultimately this information will be made available to FDA reviewers to help ensure that the opinions and preferences of those with myotonic dystrophy and their families are included the approval process for new therapies.

Providing care to the very young, the very old, and to children and adults with illnesses or disabilities has always been part of family life and is highly likely to remain so, in the United States and elsewhere. But the last 50 years have been a time of marked changes in the U.S. and other developed countries in the circumstances families face when they need to provide care to dependent relatives.

Family Caregiving Has Changed

Women, even those with young children, are far more likely to be in the paid workforce than ever before; families often do not live near relatives who in the past might have provided support; elderly relatives are surviving longer than in earlier decades but more often have multiple, age-related care requirements; and children who in the past did not survive infancy are living through childhood and even adulthood, sometimes with serious deficits and complex needs.

Outside Resources Are Scarce

Government and other support for care in the home vary greatly among countries, with the U.S. providing relatively little in terms of a safety net compared with many western European nations. (In the U.S., the Family and Medical Leave Act requires that some businesses and other employers allow 12 weeks of unpaid leave with job protection for employees who want to care for an ill family member or a new baby.)

Caregivers Experience an Array of Challenges

In June 2015, the National Alliance for Caregiving and the American Association of Retired Citizens (AARP) released a report – Caregiving in the U.S. – that showcases some of the challenges facing today’s family caregivers.

The report is based on interviews conducted in 2014 with 1,248 caregivers who were at least 18 years old and were providing unpaid care to at least one adult or child in need of special attention. (Parents of children requiring “ordinary” care – without special needs – were not part of this survey.) Among the findings were the ollowing.

One in eight Americans is a caregiver, usually for a relative:

• There are an estimated 43.5 million adults in the U.S. (or one in every eight Americans) providing care to at least one adult or child with special needs, on average providing 24.4 hours a week of care.
• Most caregivers – 60 percent – are female; 40 percent are male.
• The average caregiver age is 49.
• A large majority of caregivers – 85 percent – are providing care for a relative.

Most caregivers also have a full-time job:

• More than half (56 percent) of caregivers in this survey were employed in a full-time job in addition to their caregiving responsibilities; on average, they worked 34.7 hours a week.
• More than half (60 percent) of those surveyed said they had to make workplace accommodations, such as reducing their hours or taking a leave of absence, because of their caregiving role.

A third report no help:

• About a third (32 percent) of caregivers report they are assisted by paid help, such as an aide.
• One in three (33 percent) report they have no help at all.
• About a quarter (24 percent) of caregivers reported difficulty obtaining affordable services that would help with their caregiving in their community.
• Of caregivers providing at least 21 hours of care per week, 44 percent said respite care (with someone else taking over the caregiving for a defined period of time) would be helpful.

40 percent say burden of care is high:

• Most caregivers – 59 percent – help loved ones with at least one activity of daily living (ADL), such as helping them get in and out of beds and chairs and assisting them with bathing or showering.
• One in four caregivers (25 percent) reported assisting with ADLs was difficult.
• The most difficult ADLs with which caregivers assist involve personal care, such as dealing with diapers or incontinence (40 percent said this was difficult); helping the care recipient to and from the toilet (33 percent said this was difficult); and helping with bathing and showering (31 percent said this was difficult).
• Other caregiver responsibilities reported by those interviewed included transportation, shopping, housework, managing household finances, interacting with healthcare providers and other professionals on the care recipient’s behalf, and performing medical or nursing tasks, such as giving injections or tube feedings and providing catheter or colostomy care.
• About a quarter (22 percent) of caregivers said their own health had worsened as a result of their caregiving responsibilities.
• A high level of physical strain related to caregiving was reported by 19 percent of caregivers; 38 percent considered caregiving to be emotionally stressful.
• Financial strain resulting from caregiving was reported by 18 percent of caregivers.
• The burden of care perceived by caregivers was reported as “high” by 40 percent of survey responders, “moderate” by 18 percent, and “low” by 41 percent.

Caregiving in a DM-Affected Family Often Means Meeting Diverse Needs

MDF dystrophy (DM), particularly the type 1 form, poses specific caregiving challenges to families, as the disease affects the muscles, brain and many other organs and systems in the body.

There is often more than one person affected in a DM family – and they aren’t all affected in the same way. It isn’t at all unusual to find a middle-aged, unaffected adult caring for a spouse with adult-onset DM1, a son or daughter with juvenile-onset DM1, and a grandchild with congenital DM1.

A DM1-affected spouse may be experiencing weakness and fatigue, while the juvenile-onset-affected adult may be finding school or work unsustainable because of cognitive impairment and daytime sleepiness; and the baby in the family, with congenital DM, may require specialized care, such as respiratory treatments and tube feedings, as well as many hours a week of therapies to aid his or her cognitive and physical development.

Voices of Caregivers in DM Families

In the U.S., caregivers in DM families who have been profiled on the MDF website and who facilitate online support groups for caregivers report a combination of challenges and satisfactions with their roles, which often involve caring for spouses and children with the disease.

Diane Bade, a middle-aged caregiver of three children with DM, says her children “live vicariously through others” and that their “social networks and outlets are limited by their circumstances.” To help offset those barriers, she started an annual sleepover camp for young adults with DM at her home.

Cecilia Stearns describes having an adult daughter whose social problems, daytime sleepiness and learning disabilities, which started in her teens, weren’t recognized as DM1 until Danielle herself experienced serious complications during childbirth and gave birth to twin boys with congenital DM. “You just do what you have to do,” Cecilia says. “We’re all here and doing as well as we can. The typical retirement does not exist for us, but we’ve got our daughter and two 15-year-olds who need us. I can’t imagine my life without them.”

Regina Thompson describes caring for her adult, DM1-affected brothers: “It was perfectly normal that we’d stick together and take care of each other,” she says. “I always wanted to take care of my brothers as best I could. What I’ve learned at the MDF Annual Conferences and through other resources helps me take care of them. We’ve been dealt things we have to live with, but your perspective really can make all the difference.”

Kevin Dressler, featured in "Reaping the Rewards of an Unexpected Role", whose wife, stepdaughter and step-grandchild all have DM1, is going to be participating in an online support group for male, unaffected caregivers in DM families, the outgrowth of a community-led panel he helped lead at the 2015 MDF Annual Conference. He advises men in his situation to be patient and accept that you can’t run away but that you are not alone and can reach out to friends and support groups. Kevin’s grandchild, now 3 years old, is “blossoming” despite having congenital DM, and getting a hug from the little boy at the end of a work day offsets the difficulty of caregiving.

Even Overseas, Things Aren’t Perfect

Even in the Netherlands, where the government provides more social services for caregivers than it does in the U.S., a study published in 2014 found parents of children with a chronic illness worked fewer hours per week (if voluntary, this could be viewed as a benefit) and spent less time doing leisure activities than parents of healthy children. The researchers surveyed 576 parents of ill children and 441 parents of healthy children.

In another Dutch study, published in 2011, researchers looked at five middle-aged couples in which one person was affected by adult-onset DM1. They conducted in-depth interviews with the couples, separately and together, in two cities and three villages in the Netherlands in 2009.

They found that the partners with DM1 experienced physical, cognitive and psychosocial barriers to performing roles and participating in activities in life, leading to postponing, avoiding, adapting or giving up activities. The unaffected partners reported experiencing increasing burdens, feeling they had to do everything, including prompting their affected partners to act. In addition, couples described a lack of understanding of the DM-affected person’s condition by relatives and friends, the healthcare system and society in general. They described the healthcare system in the Netherlands as fragmented and uncoordinated, with each set of professionals looking at one aspect of DM1 at a time and no one putting the whole picture together or understanding the impact of the disease on daily life.

Resources for Caregivers

Supporting caregivers and families is one of the most important things we do. Visit the links below to explore some of the caregiver resources available on the MDF website. If you don’t find what you need, contact MDF, we’re here to help.

Join us, November 23rd, for a Meditation for Caregivers - a virtual, hour-long session with Dr. Genie Palmer, a meditation teacher and former associate professor and researcher at Sofia University. 

MDF Caregivers Support Group (notices about upcoming discussions, held online every month)

MDF Caregivers Group (a Facebook-based group)

MDF Unaffected Male Caregivers Group (a Facebook-based group)

2014 MDF Annual Conference Community-Led Track: Caregiver Focus (a 45-minute presentation discussing challenges facing caregivers)

2014 MDF Annual Conference: Advocating in the Clinic – Educating & Supporting Your Doctors (a 54-minute presentation on becoming your own healthcare advocate and educating your doctors about your needs)

Webinar: On Being a Fearless Caregiver (a 43-minute presentation on issues related to caregiver advocacy; partnering with the healthcare team and other family members; self-care; and managing the role of a caregiver)

A Three Year, Multi-Million Dollar Roadmap to Accelerate Care and a Cure

Back in February of this year, we reported out on our annual strategic planning offsite. We reaffirmed our commitment to capitalizing upon the unprecedented current interest in myotonic dystrophy to improve quality of life for people living with the disease. We noted then that we would report back when we had a final 3-year plan to share with you.

The development of that plan has been our major focus for the past few months, and we are very pleased to communicate the results to you. MDF has pledged our resources to a number of significant initiatives developed to accelerate Care and a Cure for the next three years.

Goals

The goals for the next 3 years of work are aggressive:

• Drive community-wide access to high quality DM care and shorten the diagnostic odyssey via care standards, clinical networks and improved patient access
• Deepen and strengthen the academic research bench to support more DM scientific discovery
• Expand the drug development pipeline with additional industry participation and additional drug discovery-focused research
• Expedite the therapy approval process via a targeted and immediate education and outreach effort with legislators, regulators, and other federal agencies
• Lay the groundwork for patient access to approved therapies through outreach and activism with insurers

Care

In the Care arena, MDF has identified a number of high impact initiatives to help achieve these goals, some of which we have described below.

Care Considerations

There are currently no standards of care for treatment of myotonic dystrophy, and patients and family members often find themselves educating their physicians with regard to symptoms and treatment options. The lack of standardized care protocols also makes tracking the impact of potential therapies in trials more difficult, since it can be unclear what impacts to attribute to the therapy and what is due to differences in individual participants’ care and disease course.

MDF, members of our Scientific Advisory Board, the Centers for Disease Control and others will partner to create consensus-based Care Considerations that can be used by doctors, pharmaceutical companies and federal regulators reviewing potential therapies for approval until more rigorous and comprehensive Practice Parameters are developed. We are scheduling the development of final draft considerations for mid-2016.

Research Focused on Women & DM

In order to improve understanding of disease impacts, disease course and progression in women living with myotonic dystrophy, and improve the quality of care women receive, MDF will fund the research and publication of studies focused on how myotonic dystrophy affects women. An example of such studies is the recently study that examined how women with myotonic dystrophy (DM) are impacted by pregnancy.

Expanded Fellows Award Program

To attract and retain high quality young investigators, drive retention at clinical care and research sites, support senior DM investigators and their labs and improve the quality of care delivered to people living with DM, MDF will expand the Fellows program to include pre-doctoral students, clinical fellows and fellows identified by senior research leadership.

The fellows receive training in grant writing and travel funds to attend major meetings, in addition to funding for their research projects. Two former MDF fellows have now received faculty appointments in the field.

Certified Clinical Network

MDF will explore the need and opportunity to create certification standards and a process to certify clinical centers in order to identify and support centers of excellence for people and families living with myotonic dystrophy.

Expansion of Current Care Resources and Programming

MDF is working to expand the resources and support we offer to community members now, in order to make the quality of life of people living with DM the best it can be. To that end, we will launch additional regionally-based support groups, upload more recommendations on the Find A Doctor map, expand programming at the MDF Annual Conference, and much more. MDF will also undertake a significant Care programs assessment effort, including review of the Myotonic Dystrophy Family Registry and a community survey, to identify new Care program needs and opportunities.

Cure

Most of the work in the research cure bucket is focused on making it as efficient and easy as possible for the scientific community to develop and test new drugs for myotonic dystrophy. This process is called “de-risking” and it is aimed squarely at making the numbers work for drug companies that are considering investing in the myotonic dystrophy space. For example, company X has developed an experimental compound that might help build new muscle. The company could test it on elderly people who lose muscle strength as they age, or test it in myotonic dystrophy - we want to give them every reason to choose myotonic dystrophy.

Myotonic Dystrophy Clinical Research Network Expansion

To this end, one major focus of MDF’s research plan is bolstering the capabilities of the Myotonic Dystrophy Clinical Research Network (DMCRN) - a network of six clinical sites launched in 2013 that are centrally coordinated to conduct research studies key to informing trial design and disease understanding, and to run multi-site clinical trials for myotonic dystrophy. We will do this by expanding the network from six sites to nine sites and providing the central coordinating center at the University of Rochester with additional resources for oversight and management.

This expansion is necessary to accommodate the larger clinical trials that will be required to approve a new drug for myotonic dystrophy. It will also help investigators gather data on the normal progression of the disease, which is needed to determine from a statistical standpoint how many people should be included in future clinical trials and what types of things we should measure to know if an experimental DM therapeutic is working.

Advocacy with Policymakers, Regulators & Insurers

While we are at it, we will also help to make the case to insurance companies and government health agencies that new treatments for myotonic dystrophy are cost effective and should be covered because the cost of not treating the disease is higher. To do this we will document the “burden” of myotonic dystrophy by researching the insurance claims data of many thousands of people who have been diagnosed with myotonic dystrophy and determining the average cost per year of the disease. Become an advocate now.

In the same vein, MDF will host a strategic workshop with the Food and Drug Administration (FDA), researchers and companies interested in myotonic dystrophy therapy development later this year. Our objective in bringing these professionals together is to educate them on the specific challenges and complications of myotonic dystrophy in order to inform efforts to develop clinical trial endpoints, biomarkers and advance the discovery of new therapies. Ensuring that FDA regulators and companies understand how variable and multi-systemic this disease will help inform clinical trial design. Hearing from the FDA about the rigorous process involved in approving endpoints for trials will help researchers and companies best target their biomarker, endpoint and trial development efforts. At the workshop’s conclusion, our community should be better positioned for successful therapy development and clinical trial testing.

DM Prevalence Study

We are also launching a study to determine, not just the number of people who have been officially diagnosed with myotonic dystrophy, but also how common the expanded repeat mutation is in the general population - we believe it’s likely that this study will show that myotonic dystrophy is more common than previously assumed because it often takes many years for people to receive an official diagnosis. If the disease is actually more common than thought this means that the burden associated with the disease will also higher. This information is a critical component to making the case for pharmaceutical company investment, insurance reimbursement and for policy making that affects the myotonic dystrophy community.

New Research Studies

In addition to the prevalence and burden of disease studies, we are also releasing requests for research proposals (RFPs) seeking researchers interested in identifying “biomarkers,” such as changes in blood proteins that would indicate how the disease progresses, and to developing new “endpoints,” or measurements that will demonstrate if an experimental therapeutic is working. Learn more about current research studies.

Mega Mouse

The research community has also emphasized the need to create a mouse that more realistically mimics the disease that we see in humans so that we can test therapeutic approaches quickly and efficiently - we will fund the creation of the new mouse this year.

We Need Your Help

These are some of the major initiatives MDF has launched or scheduled for the next three years. It is an ambitious and urgent array of work. You have a role to play in many of these efforts, including participating in research studies conducted through the DMCRN and other university centers, enrolling in DM patient registries, participating in surveys and helping advocate for specific legislation and initiatives that can help improve quality of life and drive therapy discovery forward.

Let us know if you would like more information or have comments on the strategic plan work described above, and please watch the Dispatch and our other communication for alerts regarding how you can support this work and other efforts on behalf of Care and a Cure. Together we will change the face of myotonic dystrophy.

05/07/2015

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

The 2014 MDF Annual Conference, which occurred Friday, September 12 and Saturday, September 13, was a singular success, featuring oversold registration, an unparalleled number of researchers, pharma and biotech partners and federal agency representatives, and a number of impressive programmatic ‘firsts.’

If you couldn't join us this year, you can view recordings of the sessions by topic area in the Digital Academy or via links in the 2014 MDF Annual Conference Agenda.

Conference Announcement: $3-5mm Research and Advocacy Investment

Advocacy, and specifically driving DM drug development and access, will continue to be a key and growing focus of MDF's work over the next three to five years. As MDF Chairman Jeremy Kelly explained during this year's conference, MDF will be making a $3-5 million investment.

It's aggressive and urgent objectives include:

• Deepening the academic bench focused on myotonic dystrophy to drive more DM discovery;
• Expanding the drug development pipeline with additional pharmaceutical partners and translational research;
• Expediting the drug approval process via a targeted advocacy effort with federal agencies and legislators;
• Influencing patient access to eventual treatments through outreach and education with the payer community.

Look for updates and more information on this advocacy initiative in the coming months.

Friends and Heroes Reception

MDF kicked off the conference with our first annual Friends and Heroes Awards Reception, hosting over 150 US Senators and Representatives, researchers, industry partners and philanthropists from the MDF community. The event, which honored MDF community leaders who have made significant contributions in support of Care and a Cure for myotonic dystrophy, was held in the beautiful Kennedy Caucus Room in the Russell Senate Office Building on Capitol Hill.

The Foundation was deeply honored to present the following awards:

• Community Leadership Award to MDF Board member and Senator Tim Kaine
• Humanitarian Award to MDF philanthropist Addy Loudiadis
• Institutional Partner Award to the National Institutes of Health, Dr. Alan Guttmacher accepting
• Outstanding Achievement in DM Research to Drs. Richard Moxley III and Charles Thornton, University of Rochester
• Outstanding Contribution to DM Clinical Care to Dr. John Day, Stanford University
• Outstanding Contribution to Rare Disease Health Policy to:
  • Senator Sherrod Brown, D-OH
  • Senator Amy Klobuchar, D-MN
  • Representative Fred Upton, R-MI
  • Representative Henry Waxman, D-CA
  • Senator Roger Wicker, R-MS

Lesli Rotenberg , General Manager of Children and Family Programming and Senior Vice President of Marketing and Communications at PBS, was a particularly gracious emcee, and community members Sarah Berman, Elizabeth Conte, Jeremy and Erica Kelly, Dr. Woodie Kessel, Larry and Hunter Lord, Dr. Richard Lymn, Teresa and Doug Schmertman, Todd Stone, Saurabh Rai and Marlo and Dr. Glenn Wiggans presented the awards.

For photos of the event, visit the MDF Facebook Page to see the conference photo album.

Grassroots Advocacy Training and Capitol Hill Visit

Advocacy was the theme of the conference and is some of the most critical work the MDF community is undertaking right now. The nation's capital provided the perfect backgrop for conference attendees to gain first-hand experience in advocating for Care and a Cure.

75 MDF community advocates attended a Friday morning briefing and then boarded buses to Capitol Hill to meet with Senators, Representatives and their staffs from more than 25 states. They educated congressional leadership and staffers about myotonic dystrophy and the importance of the MD-CARE Act, which was reauthorized just six days later !

MDF Science Workshop

MDF hosted its first science workshop, including more than 50 senior representatives from industry, the National Institutes of Health, the U.S. Food and Drug Administration, and the academic research community in a discussion entitled Measuring Drug Effects in Clinical Trials: Endpoints and Biomarkers. The workshop, the first of its kind in the US, featured opening remarks from Dr. Alan Guttmacher, Director of the National Institute for Child Health and Human Development at the NIH, and formerly of the Human Genome Project, followed by presentations from Drs. Chad Heatwole, Andy Berglund, Eric Wang, Tom Cooper, Charles Thornton, John Day , Peg Nopoulos , Richard Moxley, Darren Monckton and Gordon Tomaselli.

Dr. John Day and Dr. Charles Thornton then led a robust discussion of the status of current and potential biomarkers, endpoints, and their clinical validation, and what additional work needed to be done to facilitate the clinical trial and drug approval processes. MDF will publish a summary paper on the workshop this Fall.

New Video! Living with DM: The Community Speaks

The conference opened with a new video featuring MDF community members providing moving perspectives of the DM journey and a call to action to help drive Care and a Cure. Click here to watch the 5-minute video.

Keynote Address from Acting US Surgeon General

RADM Boris Lushniak, MD,MPH Acting United States Surgeon General and the ‘Nation’s Doctor,’ opened the conference with an inspirational overview of the importance and specific roles of advocacy, education, research and clinical care in helping improve the quality of life of families living with this disease and driving efforts toward treatments and a cure. He acknowledged the importance of hope and the importance of the current DM journey, and welcomed the community to Washington, DC.

New Breakout Sessions on Vision and Emotional Health

Clinicians and researchers from Stanford University, Washington, DC, University of Iowa and University of Sherbrooke offered outstanding breakout sessions on DM and Emotional Health: Depression and Anxiety, Vision and Eye Health and a best-in-class GI Health session. Visit the MDF Digital Academy to view videos of these sessions, or the 2014 MDF Annual Conference agenda to view and download the PowerPoint presentations.

Expanded Juvenile Onset Adult Ambassadors Track

The JOA Ambassadors track included session break outs by age group, as well as a shared session for JOAs and their caregivers. Generous support from the Cohen Family Trust and AHLIFE (A Healthy Life for Everyone) again provided partial travel scholarships in support of JOA attendance.

Other Conference Programs

An Isis Pharmaceuticals clinical trial update from Dr. Frank Bennett, a preconference adaptive yoga session led by Dr. Ariele Foster, a networking lunch organized by table topics, support group and TeamMDF volunteer meetings, a Kostume Karaoke party and trivia contest at Friday night’s reception and a Twilight Monuments Bus Tour rounded out the action-packed conference weekend.

MDF Announces 2015 MDF Annual Conference Location!

To expedite our advocacy agenda and further build on our community's success in advocating for the recent reauthorization of the MD-CARE Act , MDF will return to Washington, DC, from September 18-19, 2015, for the 2015 MDF Annual Conference. This conference will be held in conjunction with a joint FDA/NIH workshop that we will be hosting. Watch for updates in the coming months. We hope to see you there!

09/26/2014

The Myotonic Dystrophy Family Registry currently has over 1,900 participants, making it one of the largest and most up-to-date myotonic dystrophy (DM) registries in the world. If you’ve been diagnosed with DM1 or DM2, including congenital or juvenile onset, or are the primary caregiver for some who has, and you haven’t already joined the Registry, we need you!

By participating in the Registry you can help researchers from industry and academia identify potential clinical trial participants and research study subjects, and increase understanding of the impact and complexity of this disease.

The Registry is patient-driven, which means you’re in charge of your information. You can opt out of the Registry at any time, and you can also visit the Registry website to review de-identified (anonymous) data and information the same way that registered researchers do. Your individual information is kept completely confidential. Data in patient registries is typically considered out of date and less useful if it is not updated at least every 18 months, so we’ll remind you to log back into the Registry to review and update your survey occasionally.

Click here to go to the Registry website, read and sign the consent form, and get started.

Questions? Contact the Registry Coordinator for more information.

08/20/2014