Healthy Outcomes for People Living with Congenital Muscular Dystrophy

Cure CMD’s mission is to advance research toward treatments for the congenital muscular dystrophies and empower those living with CMD through engagement and support of our community.

Congenital muscular dystrophy (CMD) is a group of ultra-rare diseases caused by genetic mutations that lead to global muscle weakness at or soon after birth. While there are dozens of congenital-onset muscle conditions, the term CMD is generally used to define five primary subtypes: Collagen 6-Related Dystrophy, alpha-Dystroglycanopathy, LAMA2-Related Dystrophy, LMNA-Related Congenital Muscular Dystrophy, and SELENON-Related Myopathy. The estimated global population of affected individuals with a primary subtype of CMD is between 1:25,000 and 1:50,000.

Although each of these five subtypes is distinct in terms of genetic cause and pathological mechanisms, there is significant overlap in symptom onset and progression, and adverse medical events. Affected individuals experience global muscle weakness, pulmonary insufficiency, feeding difficulties, scoliosis, and joint contractures. These symptoms cause affected individuals to lose or never gain the ability to walk, require breathing support via mechanical ventilation, require alternative feeding methods, and often require surgical interventions. There are currently no approved treatments for any of the CMDs, and a number of disease-associated life-threatening events can cause premature death.

As a result of progressive symptoms, affected individuals experience serious adverse events (SAE) with no universally implemented mode of treatment given the rarity of CMD and the average clinician’s limited exposure to this condition. A critical lack of consistent, proactive care implementation when early signs of an impending SAE occur lead to extended hospitalizations and sometimes, death. Examples include:

• Respiratory illness without adequate proactive symptom management

• Episodes of Hypoglycemia and other emergent complications related to low BMI

• Fatalities due to complications from a variety of other SAEs: it is critical that we better understand: 1) What are the causes of death, 2) Are these causes directly related to the underlying pathophysiology of CMD, and 3) What can be done to provide better surveillance and early intervention to mitigate SAEs, including death. 

Based on 1,984 retrospective serious adverse event reports collected from participants in the Congenital Muscle Disease International Registry (CMDIR), we know that nearly 80% of CMD-affected individuals experience at least one SAE, with more than 50% experiencing 2 or more more SAEs, including death (11% reported).

This project will use real-time reporting, electronic medical records, and machine learning to provide participants with up-to-date alerts about impending SAEs, as well as evidence for expanding care protocols to be more responsive to SAEs with readily accepted adaptation by both the affected community and their care providers, ensuring a greater number of positive health outcomes for those living with congenital muscular dystrophy.

Our solution provides a means of collecting ongoing monitoring data for symptoms and high risk activities that may lead to a SAE. As new data is submitted, through real-time patient/caregiver report and electronic medical records, our system applies programmatic algorithms (machine learning) that codify the accumulated experience of primary and clinical caregivers to anticipate and identify potential high risk scenarios (injuries, infectious exposures, oncoming health degradation due to lapses in proactive care surveillance, etc). Our solution provides real-time alerts to primary caregivers of potential impending risks of SAEs, and access to expert clinicians to help guide solutions to advise on more proactive steps to avert those events. 

This solution aims to answer the following questions:

1. Can a significant portion of serious adverse events (SAEs) among patients with congenital muscular dystrophy be prevented through: 

• Early recognition of an impending SAE and immediate intervention by caregivers and healthcare professionals to reduce the chances of the event becoming life-threatening

• Adherence to existing care recommendations to prevent adverse events

• Expansion of existing care recommendations to better address SAEs

• Better patient community awareness of higher risk scenarios

1. Can fatalities be averted through more timely critical care intervention where both the timing and scope of care are informed by a more detailed view of the patient’s current health, in particular, with identification of higher health risk periods due to:

• Lapses in compliance to maintenance protocols

• Identification of potential high risk exposure scenarios

• Better monitoring of early warning signals during post-high risk periods

With the ultimate goal of answering these questions:

• When and what monitoring and care protocols should be initiated during the course of disease progression, and especially during periods of elevated health risk?

• When is emergency care intervention called for considering the more fragile health of CMD patients?

• What should be the scope of emergency care and hospital admission?

This project will demonstrate the impact of providing caregivers and providers with increased awareness of incidents that have a high risk of causing of SAEs: periods of high health risk or periods in which the patient’s resiliency might be compromised. Awareness of these circumstances will help affected individuals and their caregivers conduct more careful monitoring of symptomatic warning signs, to make more timely decisions regarding initiation of emergency care, and to serve as a better informed collaborator.

We cannot imagine a more dire outcome than when existing care recommendations fail to prevent a serious adverse event, including death. In the absence of more detailed and recent monitoring data, care providers with limited experience treating patients with congenital muscular dystrophy have no basis for pursuing a more aggressive and preventative treatment approach. We will fill both the general knowledge gap in addressing SAEs, and the critical role caregivers have in monitoring for early signs of an impending SAE in periods of higher health risk, empowering them to bring their case to care providers in a more timely fashion.

We have provided a means of reporting retrospective adverse events to the CMD community for more than 14 years, with approximately 1,700 data contributors. Through this data, we have identified a number of high-risk events that we’ve communicated to clinicians and researchers, supported the publication of several papers that promote healthier outcomes based on our data, and provided 1:1 support for those experiencing SAEs who reach out for assistance. This project is the logical culmination of our prior work into a broader, more comprehensive and consistent service.

Our solution aims to identify potential serious adverse events before they happen, by providing a means for caregivers to report symptoms or events that could lead to an SAE, receive early warning of potential high risk periods, and adapt monitoring to detect events in early stages, possibly predicting the onset of a SAE. With this new insight, caregivers can initiate remedial treatment earlier, potentially requiring less costly interventions such as an early round of antibiotics or antiviral rather than an emergency department visit or hospital admission.  

There are many conditions that make increased susceptibility to SAE exposure much greater for them than for those who do not live with a chronic disease. Our solution can be adapted to any condition with a similar risk profile.

We seek funding to expand our current capabilities, which currently only include data collection on retrospective events and support in isolated cases, to the following areas: 

• Expand monitoring capabilities specific to user feedback, to make it easier for caregivers to report symptoms and other indicators of a potential SAE. 

• Expand analytics to identify additional health risks based on input from our clinical experts who have significantly more experience treating CMD than the average clinician

• Add machine learning to our current adverse event identification processor, leveraging patient reporting of historical adverse events, patient health state, symptom timings and related circumstances

• Expand our notification capabilities with additional notification types (e.g. high, medium, low) based on caregiver preference, baseline disease state, and risk exposure

• Expand our pool of subject matter experts and clinical practitioners into a more formal steering committee to guide the development of monitoring (data collection) and analytical algorithms that generate warnings and alerts to caregivers

• Develop a means for caregivers to submit ‘victories’ – brief stories describing events where our solution helped them anticipate and prevent or mitigate a serious adverse event, or recognize a dangerous health trend

As the only nonprofit organization solely dedicated to supporting the five primary subtypes of congenital muscular dystrophy, Cure CMD, and our clinical advisors, have extensive experience in collecting and analyzing data from the CMD community through management of the Congenital Muscle Disease International Registry (CMDIR) since 2009. In addition to providing a robust system for patients and their caregivers to report about their disease experience, we provide 1:1 support when a community member experiencing a serious adverse event reaches out, communicating care recommendation protocols and providing liaison with clinical experts when their local team lacks CMD expertise. Through all of these services, we also work closely with our clinical experts to better characterize disease progression and the occurrence of SAEs, which makes this project the next logical step in providing early intervention support to  the broader CMD community.

Rachel Alvarez has been associated with Cure CMD since its inception in 2008, first as a volunteer providing IT and communications support, then hired as the organization's first employee in 2012 to manage the CMDIR, and ultimately as Executive Director since 2016. Rachel is an affected individual living with CMD, who after a 2007 chance meeting in the emergency department for untreated respiratory failure, encountered Cure CMD’s soon-to-be cofounder, Dr. Anne Rutkowski. Dr. Rutkowski not only helped ensure Rachel’s eventual recovery and discharge in the face of a complete lack of understanding about her disorder among her care providers, but also forged a path to genetic confirmation of her then-undiagnosed neuromuscular disorder.  Now, Rachel’s personal mission is to ensure that no one in the CMD community finds themselves in a life-threatening situation like she did, with no means to advocate for proactive and aggressive care interventions that make a meaningful difference in their health outcome. Learn more about Rachel’s CMD journey at: https://ncbi.nlm.nih.gov/pmc/articles/PMC8958917/.

Our technical team at Ordinal Data is led by Bill Tulskie, who has over twenty years’ experience in developing systems for healthcare and life sciences research and fifteen years’ experience developing, implementing, and supporting research studies with a focus on rare diseases, and on developing analytical tools for investigation of patient and clinician reported data.

At the heart of Cure CMD’s mission are the many voices of the CMD community who continue to shape our priorities in service to them. Second only to the community’s desire to identify pharmacological treatments for this disease, is the ongoing, direly expressed need for a means to predict and prevent serious adverse events and negative outcomes. Currently published care recommendation guidelines are not enough – a more proactive approach is desperately needed.

Over the next five years and beyond, we expect that this solution will: 

• Save lives that would otherwise be lost to serious adverse events

• Prevent and/or reduce the occurrence of emergency room visits and hospitalizations

Reducing fatalities and hospitalizations, and preventing emergencies will have dramatic and obvious positive impacts on the lives of people living with CMD. Proactive engagement of caregivers will provide a much greater degree of control in managing their loved one’s health, and enable them to make better choices that improve the quality of life for everyone in their family.

We also want to provide a means for caregivers to share their ‘victory’ stories – how use of our system made a tangible difference in the management of a high risk event, giving other community members confidence to utilize the system themselves.

Finally, we foresee that the data we collect about high-risk events and outcomes will be used to create more effective and specific care recommendations, giving the community something tangible to share with their local healthcare providers, well in advance of a serious adverse event.

Serious adverse events among those living with congenital muscular dystrophy often begin with a traumatic episode that takes everyone by surprise. Then, the event scenario plays out in a way that is beyond the caregiver’s control – a horrible experience.  Caregivers do not currently have a means to systematically collect data that monitors key indicators of their loved one’s health and report events and exposures to high risk events, let alone access to crowdsourcing of these potential events among many community members to the benefit of everyone. 

Our solution changes that. We currently only provide a means to collect data on prior adverse events, but with funding, we will be able to collect real-time, current monitoring data and exposure event reports.The system will process collected data on an ongoing basis to identify potential risks and provide health risk alert notifications to caregivers with valuable, actionable feedback that leverage clinical expertise beyond what most community members currently have access to. It will also provide caregivers with reminders to keep up with ongoing health surveillance monitoring and reporting.

Our approach has a very straightforward theory of change: make it easy to collect the right data, process that data to effectively identify health risks, and then warn caregivers of impending risks.  

We expect our pilot testing to confirm that caregivers will make the up front time investment in reporting and monitoring to take control and avoid the tragedy and trauma of serious adverse events.

1 full time
2 part time
3 contractors (Ordinal Data)
10 volunteers (clinicians expert in CMD who provide medical advisory and guidance during community SAEs)

While we have been collecting data about serious adverse events since 2009, and continue to provide a less streamlined avenue for 1:1 support of the CMD community when they experience an SAE, we have only begun developing this particular real-time intervention solution in the last year, in response to the increasing need and as new technologies have become available.

Our team is composed primarily of CMD stakeholders – those for whom improvement in medical outcomes is crucial, and the varied voices of many diverse backgrounds continue to inform our work. We are aware of the innate racial and cultural bias that comes with voluntary participation in any study or project, particularly related to health outcomes, and prioritize the ongoing work of identifying paths toward more equitable access for everyone living with CMD. We welcome and value any and all participants in this project, regardless of cultural or socio-economic background, but understand that the impact we can make is just a tiny part of the entire system of health care disparity that exists.

Our mission is to advance research toward treatments for congenital muscular dystrophy and to empower those living with CMD through support and engagement of our community.

Cure CMD is a U.S. registered 501(c)3 nonprofit organization serving the global congenital muscular dystrophy community, that includes affected individuals, caregivers, family and friends, researchers, clinicians, industry and policy makers. With a reach of more than 5,000 actively engaged stakeholders, our small but mighty team provides outreach and educational resources with the power to improve the lives of those living with CMD. We also provide a means to crowdfund peer-reviewed research projects that advance the CMDs toward approved treatments. But perhaps most importantly, we offer a home to those affected by CMD to learn, share victories and losses, and give and receive support in a life that so often silos them. Prior to becoming involved with Cure CMD, most living with this devastating disease will have never met someone else traveling a similar journey. In providing that conduit, we are transforming their lives to include hope, knowledge, and the ability to effectively and confidently advocate for their needs. 

Cure CMD has grown from an all-volunteer foundation in 2008 to a full-service organization ever-evolving to meet the needs of our community. 80% of our funding comes from individuals affected by or connected to someone living with congenital muscular dystrophy. Our goal in applying for funding opportunities such as this one, is to reduce the burden of financing our mission on those affected, through the development of partnerships with foundations, institutions and corporations with mission overlap, and individuals with no connection to CMD that have an affinity for promoting care, support, and healthy outcomes for those living with a rare disease. 

Retrospective data collection has been at the heart of our patient registry since 2009. We have funded the majority of registry expenses through Cure CMD’s operating budget, but have also received periodic support from the National Institutes of Health, the Chan-Zuckerberg Initiative, the Patient Centered Outcomes Research Institute, a number of private foundations, and several pharmaceutical companies interested in developing treatments for CMD. There are also two other advocacy organizations who have co-funded ongoing registry operations since inception: A Foundation Building Strength for Nemaline Myopathy, and Team Titin. 

Ideally, once we are able to move past the prototype stage of this project, we will identify additional funding partners who find value in helping to grow this work of improving healthy outcomes for those living with CMD. Our organization has a long track record of forging and developing such relationships, and we are confident in our ability to do so for this project.