Our Research Strategy
Charley’s Fund focuses on rapidly directing funding to the most compelling medical research and solving problems that stand in the way of new treatments. To date, we have directed nearly $45 million to research. Our work to beat Duchenne involves a two-pronged approach:
Support promising new therapies that are being developed right now
Develop tools and resources that help our entire research field work smarter and faster going forward
For highlights of our work, read about the projects below.
Driving New Solutions
"Of Mice and Measures"
Background + Problem
It’s been said that if kids with Duchenne were mice, they’d be cured ten times over by now. While that is no doubt an exaggeration borne from frustration, it is true that our community has generated an abundance of mouse studies with “promising” results, yet scant treatment options for people with Duchenne. One major reason we have trouble translating promising research results into actual therapies is the shortcomings of how preclinical methods and models are used by DMD researchers in both academia and industry. Our models and methods play a pivotal role in the drug development pipeline: they provide the crucial ‘gateway to the clinic’. And yet, there is little to no consistency in how even leading labs across the world use them. The consequences of this are severe: On the one hand, we risk advancing the wrong drugs into clinical trials, which wastes time, funding, and research resources. On the other, we risk “missing” good, effective drugs simply because the wrong preclinical test was used. We need to establish clear, best practice guidance for our mouse models: which mouse should be used, in which way, and with which measures and protocols depending on the hypothesis being tested?
In 2017, in collaboration with leading experts in the DMD community, Charley’s Fund launched an initiative to tackle this issue. Of Mice and Measures (“OMAM”) is a collaborative, ongoing effort that brings together experts from academia and industry — currently more than 20 institutions are on board — to improve the decision-making process for which drugs should advance to clinical testing. OMAM grew out of our 2015 “Project Goldilocks” program, which explored a promising newer mouse model — the D2.B10-DMDmdx/J (‘D2/mdx’), hypothesized to recapitulate human disease better than the commonly used Bl10/mdx. The data generated by Project Goldilocks raised important questions, and OMAM is in the process of developing possible solutions. In 2017, we convened a scientific organizing committee, organized working groups, and collected and analyzed data in advance of a two-day workshop to discuss findings and next steps. The results of this work are presented in a workshop report (published here) and a WMS poster presented at the 2018 meeting in Argentina.
Today, we are at the ‘tail end’ of finalizing design for a critical natural history study that will help gather key data about both the new D2/mdx mouse as well as the classic ‘gold-standard’ Bl10/mdx mouse. The goal is to capture this in new “SOP” and best practice documentation for the D2/mdx mouse as well as updated SOPs for the Bl10/mdx where appropriate. All this will be made available to the full DMD research community.
Background + Problem
Our co-founder Dr. Benjy Seckler has always said, “The only thing worse than not having an effective treatment is having a treatment that works but not being able to show it.” In order to determine which experimental drugs are actually benefitting patients, we need reliable and objective outcome measures that can tell us relatively quickly whether a drug is inducing a positive change. The most common measures used today are far from ideal, which means clinical trials are slower, more costly, and less efficient than they should be.
It can take a very long time to prove that an experimental treatment extends or improves life. A drug may preserve or strengthen muscle mass, but it can take many months or even years to become evident through changes on outcome measures that are most commonly used in clinical trials such as the six-minute walk test or 4-stair climb. Without biochemical markers that change in response to drug treatment, access to new drugs is dramatically slowed. What's more, we also need measures that better reflect how a patient fares on meaningful activities of daily living, like getting up from the floor, lifting a fork to eat, or rolling over in bed —crucial quality-of-life activities that become compromised by Duchenne.
We are working on the development of two outcome measures that could significantly improve our collective ability to determine whether a drug is having its desired effect.
Electrical Impedance Myography (EIM) utilizes a small hand-held device to run a high-frequency electrical current through a muscle. The current changes that occur provide insights into the health and integrity of the muscle. EIM is painless, relatively inexpensive, takes seconds to perform, and can be used on patients of any age. Charley’s Fund is collaborating with EIM founder Dr. Seward Rutkove to assess EIM’s suitability as an outcome measure for Duchenne. With our support, Dr. Rutkove has completed critical studies to confirm EIM’s reliability, consistency, and ability to differentiate healthy muscle from diseased muscle, and to generate preliminary findings about its ability to detect disease progression in a relatively short period of time. You can read more about EIM in this peer-reviewed journal article as well as a Q+A we hosted with Dr. Rutkove.
In parallel, we’re working on another new tool with potential to measure how a patient is progressing in a novel and highly sensitive way. With the Duchenne Video Assessments System, families or caregivers use a smartphone app to record videos of patients completing everyday tasks. Trained physical therapists evaluate the videos according to a rigorously developed, standardized scoring system. This tool is unique because its methodology focuses on the quality of movement or ease with which patients complete tasks of everyday life over time — not just how quickly they perform them. Currently, we’re supporting the refinement of the scoring system as well as a clinical study to gather a library of sample videos that will be used to confirm the scoring system’s reliability and validity. Read more about the Duchenne Video Assessments tool in this Q+A with co-founder and mom of Aidan, Mindy Leffler.
The Duchenne Program
Background + Problem
Since Charley was diagnosed with Duchenne in 2004, he has traveled on an airplane each year to visit a clinic that provides the comprehensive, interdisciplinary care that no place nearby offered. And when a clinical trial opportunity arose, he had to fly to yet another city — this time once a week — to participate. Charley is not alone. Many patients in the Northeast Corridor have found the region lacking when it comes to comprehensive, integrated care and clinical trial opportunities. This problem is more than an inconvenience. Families without the resources to travel are stuck with suboptimal care and, as a result, worse health outcomes.
It’s also a big problem for research: The Northeast is a vibrant hub for preclinical research activity, but many clinical trials like Charley’s were not being conducted in the region. Some patients would travel to be included in trials, but most were not able to participate at all. The opportunity to be a part of advancing research was out of reach for too many people, and the development of new drugs was slowed. This was untenable — kids with Duchenne do not have time to spare.
In 2015, Charley’s Fund undertook a multi-year due diligence investigation to determine what it would take to build a world-class DMD clinic and research site in the Northeast. We researched best practices, explored the challenges and opportunities that launching a new clinic would present, searched for a host site that would serve as a partner in innovation, and identified a visionary who would serve as the founding clinic director. After years of careful research and planning, The Duchenne Program at UMass Medical School officially launched in July 2018. It is the first of its kind in the Northeast exclusively dedicated to extending and enhancing the lives of people with Duchenne muscular dystrophy and its close cousin Becker by advancing cutting-edge care and research. It’s also the first of its kind here that supports people with Duchenne from infants to adults with comprehensive, coordinated care all in one place.
We are honored and excited to be working closely with Dr. Brenda Wong and UMass leadership to build The Duchenne Program over the coming years. We are committed to creating a true hub for Duchenne, a place where knowledge is discovered, created, and shared to help all people affected by Duchenne live the longest, fullest, best lives they can. For more information about this innovative model, visit the program’s website.
Selective Androgen Receptor Modulator
Background + Problem
Duchenne has one cause, but experts agree that an effective treatment will be made up of multiple medicines working in concert to keep the disease under control. A critical component of this “cocktail” is a treatment that enables muscles cells to regenerate and grow. When a healthy person exercises, muscle cells die and then regenerate. But for kids with Duchenne, once the muscle cells die they do not revive. Kids lose muscle mass as they get older, and it never comes back. As people with Duchenne go about their daily lives, healthy muscle dies off and instead of regenerating, it turns into scar tissue (fibrosis). A successful suite of treatments for Duchenne will not only stabilize the muscle membrane, but also help build muscle mass to maintain and increase strength.
As part of our quest to help advance molecules that attack Duchenne on various fronts, Charley’s Fund got in touch with a company that was developing a SARM (selective androgen receptor modulator) to treat cachexia, cancer-induced muscle wasting. The drug aims to increase muscle mass. Charley’s Fund supported several studies in the DMD mouse model to see if this compound might be beneficial in our disease population, and the results were encouraging. But then the company discontinued development of the drug for business/strategic reasons, and the drug was left without a path forward.
We anticipated that this could happen, as it is not uncommon for biopharma companies to stop developing a particular molecule due to shifting business priorities. Our contract with the company stipulated that should they decide to shelve the drug, Charley’s Fund could take over the rights to develop it. We exercised that right and then financed additional work to keep moving the drug toward a clinical trial for kids with Duchenne. In late 2018, a Cambridge-based company that is singularly focused on developing treatments for Duchenne licensed the rights to develop the compound. This company has the drug development expertise and resources necessary to advance the program into clinical trials. We receive quarterly update reports from the company to ensure they are moving along without undue delay.
The Race to Yes
Background + Problem
When we started Charley’s Fund in 2004, our singular goal was to get new treatments into clinical trials. Thankfully, a tremendous amount of progress has been made on that front. Fifteen years ago, there were zero clinical trials for people with Duchenne; today there are dozens. However, with this historic progress comes new challenges. One of those challenges became evident when an emerging treatment had been tested in boys with Duchenne for several years. At first, it was the parents who started to notice that their kids were doing better than expected. Then, upon examination of the data, a broad swath of DMD experts (scientists and clinicians) agreed that this treatment met the criteria for accelerated approval. Yet the regulatory process dragged out for months, and then years. The FDA reviewers tasked with evaluating the drug failed to provide clear guidance to the company on how to proceed in light of the positive initial data. They raised question after question that delayed wider access to the medicine through accelerated approval, even though 36 esteemed DMD experts penned a letter outlining why, in their collective opinions, doctors should be allowed to prescribe this drug.
We joined forces with Team Joseph, a Michigan-based organization, to launch The Race to Yes, an independent movement powered by the Duchenne community and concerned public to help bring about a faster, more efficient regulatory process for DMD treatments. The Race to Yes pursued a three-pronged approach to achieving this end: direct conversations with the FDA, engaging elected officials, and public awareness/activism. We first sprang into action when we learned that the FDA was not providing Sarepta with clear and timely regulatory guidance for the clinical development of eteplirsen and follow-on exon skipping drugs in the company’s pipeline. Over the ensuing two years, we helped shine a bright light on the regulatory process to help ensure that our government is acting in the best interests of the people it serves. Ultimately, eteplirsen (now called Exondys 51) gained accelerated approval, and now another exon skipping medicine for a different subset of patients (golodirsen) is under review. Importantly, the FDA reviewers who decide whether a drug should be approved now have a better understanding of critical issues such as the natural history of Duchenne, the role of dystrophin in disease progression and modification, and the nuances of various outcome measures.