"A holy-grail of physician-investigators engaged in both ALS patient care and research has been the efficient and effective use of clinically-derived data for research purposes. To address this critically unmet need, we have partnered with Epic (the maker of the most widely used electronic health record [EHR] system) to build the ALS Toolkit. This resource will permit broad sharing of de-identified clinical data in a regulatory-compliant manner."

Michael Benatar, Professor of Neurology at the Miller School of Medicine of the University of Miami, was awarded an MDA Clinical Research Network Grant totaling $916,261 over three years to support the multicenter deployment of the ALS toolkit, a module built into the Epic EHR that aims to facilitate structured data collection for research and improve quality of care.

Clinics are critical to ALS patient care, leading to improved quality of life and prolonged survival. Clinic visits can take several hours with substantial clinical data collected; however, these data have limited utility for research purposes because of the unstructured way in which the data are collected. The ALS toolkit will provide a platform for standardized data collection across clinical sites, which could obviate the need for separate research visits and reduce the burden on patients and physicians.

"Our new approach will continue development of a novel approach to delivering larger, possibly up to full-length, dystrophins."

Jeffrey Chamberlain, Ph.D., Professor and McCaw Endowed Chair of Muscular Dystrophy at the University of Washington School of Medicine, was awarded an MDA restricted research grant totaling $471,693 over two years to develop improved dystrophin vectors that can deliver larger and more functional dystrophins to muscles throughout the body in patients with Duchenne muscular dystrophy (DMD).

Current approaches for DMD gene therapy rely on AAV delivery of micro-dystrophin or gene editing tools, which each produce smaller than normal dystrophins. Dr. Chamberlain plans to develop improved dystrophin vectors than can produce larger and more functional dystrophin to muscles of DMD patients. If successful, this technology would be applicable to any DMD or Becker’s muscular dystrophy (BMD) patient.

"There is an enormous need for a better understanding of the clinical, demographic, and genetic features that underlie the clinical variability seen in patients suffering from ALS."

Jonathan Glass, M.D., Ph.D., Professor of Neurology at Emory University, has been awarded an MDA restricted research grant of $137,228 for one year to continue to provide the ALS research community with data, biofluids, and tissues from deeply phenotyped ALS patients and people without ALS who participate in Emory’s Clinical Research in ALS (CRiALS) project.

There is significant phenotypic and genetic heterogeneity observed among persons with ALS, which may partly explain some of the failures in clinical trials. The CRiALS database is considered one of the most valuable resources for ALS research with a large and extremely well characterized patient population. Dr. Glass’ work could pave the way for better defined disease features and ultimately clinical trials targeting specific patient populations.

"The overall goal of this project is to develop new and innovative mobile device-compatible methodologies based on low-cost easily obtained accelerometers and machine learning algorithm technologies with the objective of providing cost-efficient tools to allow consumers, clinicians and researchers to better evaluate the community mobility of people with neuromuscular diseases in clinical and research settings."

Erik Henricson, Assistant Professor of Physical Medicine and Rehabilitation at the University of California, Davis, was awarded an MDA Clinical Research Grant totaling $427, 822 to develop an automated sensor technology to evaluate ambulatory function in people with neuromuscular disease in the home, community, and clinical settings.

A number of potential therapies are in clinical development for neuromuscular diseases, with a growing recognition that treatment benefit will be greater the earlier it is initiated. Although many children are being diagnosed as toddlers or younger, they are rarely included in clinical trials because of the lack of reliable clinical endpoints for longitudinal follow-up.

Dr. Henricson has developed a machine learning algorithm that calibrates data from a single small sensor to determine gait characteristics, even in children, with a high degree of accuracy. In this project he will work with male and female patients with DMD, BMD, SMA, FSHD and CMT to further the development of this reliable, unobtrusive, easy-to-use, portable, and cost-effective technology that pairs with the patient’s own mobile device.

"Cardiomyopathy is a prominent feature of many neuromuscular diseases including Duchenne muscular dystrophy (DMD)."

Qi Lu, M.D., Ph.D., director of the McColl Lockwood Laboratory for Muscular Dystrophy Research at Atrium Health in Charlotte, NC, has been awarded an MDA restricted research grant totaling $350,153 over two years to develop a way to reduce the death of heart muscle cells known as cardiomyocytes and improve their capacity to regenerate.

Heart failure is a common cause of death in people with all types of muscular dystrophy, due to accumulation of fibrosis that leads to poor regenerative capacity in the heart muscle, and ultimately heart failure. Dr. Lu’s research may provide new hope for all heart failure patients.

"We will conduct crucial statistical analyses to uncover ALS risk factors and the cause of ALS."

Hiroshi Mitsumoto, M.D., Wesley J. Howe Professor of Neurology at Columbia University Medical Center, has been awarded an MDA restricted research grant of $54,784 for one year to support continuation of three National Institutes for Health and Centers for Disease Control and Prevention-funded studies, for which MDA has already provided supplemental funding.

Studying the epidemiology associated with ALS is critical for developing a better understanding of the disease. Dr. Mitsumoto will continue to analyze large cohorts of ALS patients to identify potential environmental risk factors in ALS. This grant will also support a personalized clinical trial to determine if a Japanese herbal medication can target and improve muscle cramps in individuals with ALS.

"To accelerate therapy development, we designed the first Platform Trial for ALS in the world. Traditionally, each trial evaluates only one drug at a time. Platform trials, instead, are trials where multiple drugs are tested in multiple treatment arms at the same time."

Sabrina Paganoni, Assistant Professor of Physical Medicine and Rehabilitation at Harvard Medical School and Co-Director of the Massachusetts General Hospital Neurological Clinical Research Institute, was awarded an MDA grant totaling $500,000 over three years to support the HEALEY ALS platform trial.

Recent breakthroughs in ALS science have generated a rich pipeline of promising therapeutics and new hope that effective treatments may be within reach. However, the typical clinical trial design is inefficient, expensive, and leads to long delays between drug discovery and trials. Platform trials enable the testing of multiple therapeutics within an existing infrastructure, allowing for addition of new treatment regimens and reduced number of placebo controls compared to conventional trials.

This grant will support the infrastructure needed to sustain the HEALEY ALS platform trial, which will facilitate the testing of novel therapies and also create opportunities to test novel biomarkers and tools that can potentially provide answers more quickly than traditional endpoints.

"Recent studies in human disease support the notion that loss of such TDP43 function is compromised as an early event in neurons of cases of ALS-FTD. If so, a promising therapeutic strategy would be to complement the loss of TDP-43 splicing repression in neurons of ALS-FTD."

Jeffrey Rothstein, M.D., Ph.D., director of the Robert Packard Center for ALS Research at Johns Hopkins University School of Medicine, has been awarded an MDA restricted research grant of $54,785 for one year for investigator Philip C. Wong, PhD, professor of Pathology, to develop an adeno-associated virus (AAV) delivery method to validate a gene therapy strategy for ALS and frontotemporal degeneration (FTD).

TDP-43 pathology is a major pathological hallmark of nearly all cases of ALS yet the full picture of how TDP-43 pathogenesis affects neurons is not clear. The proposed strategy is hoped to compensate for the loss of normal RNA generation due to dysfunction related to TDP-43.

"With drug development for myotonic dystrophy 1 (DM1) progressing rapidly, "access to genetic testing could become a significant bottleneck"."

Charles Thornton, M.D., Saunders Family Distinguished Professor in Neuromuscular Research at the University of Rochester Medical Center, has been awarded an MDA restricted research grant of $49,953 for one year to make improvements in technology for genetic testing of DM1, a relatively common form of muscular dystrophy.

Current genetic testing methods for individuals with DM1 are expensive, labor intensive, have limited throughput, and lack the precision needed to determine the size of the expanded CTG repeat. Dr. Thornton is developing a novel method of genetic analysis that is simple, amenable to high throughput, and able to determine repeat expansion sizes. This technology could be important for rapidly identifying the many thousands of people in the U.S. that will require genetic testing when treatments for DM1 are approved.

"An open Charcot-Marie-Tooth genetics data resource could help expedite CMT research, from gene identification to drug discovery and development."

Stephan Zuchner, M.D., Ph.D., chairman of the Dr. John T. Macdonald Foundation Department of Human Genetics at the University of Miami School of Medicine in Florida, was awarded an MDA research infrastructure grant totaling $384,967 over three years to expand and make more widely available resources to streamline gene identification and therapy development efforts for Charcot-Marie-Tooth disease (CMT).

Approximately 40 percent of people with CMT do not have a confirmed genetic diagnosis, highlighting the need for a continued focus on gene identification efforts for CMT. Since the most common causative genes for CMT have already been identified, there exists a need for genetic analysis across larger cohorts of patients to find rare causes of disease. In collaboration with the Inherited Neuropathy Consortium, Dr. Zuchner has developed a genomic data infrastructure platform. This open CMT genetics data resource allows for aggregation, archiving, analysis, comparison and sharing of genetic data among many laboratories and institutions.

The resource will accelerate CMT research from gene identification to therapy discovery and development. Making such data available to CMT researchers in the United States and around the world could improve diagnostic processes, guide functional studies and drug discovery, and build the foundation for the patient selection process necessary for well-designed clinical trials.