The ALS Association has announced $1.4 million in new funding awarded to advance the search and discovery of biomarkers correlating with key clinical and pathological aspects associated with ALS disease progression. The new funding will be paired with a $539,000 match donation intended for support of ongoing ALS research.
There is currently no cure nor any life-prolonging treatments for ALS (amyotrophic lateral sclerosis), a progressive and devastating neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body, and the progressive degeneration of motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost, and people with ALS gradually lose their ability to initiate and control muscle movement, a progression that typically leads to total paralysis and death within two to five years of diagnosis.
There is currently one FDA-approved drug for the treatment of ALS — riluzole (Rilutek), which improves survival by just two to three months. Other treatments are available that relieve the symptoms associated with ALS and improve the quality of life for patients living with the disease by providing comfort to the patient. However, there is an urgent need for improved therapies.
The recently announced ALS Association awards are earmarked to fund three projects, each of which focuses on ALS biomarker discovery. Support for these projects is part of the biomarker discovery initiative identified and described in The Association’s strategic plan and aligns with other efforts already undertaken, for example ALS ACT, a novel academic-foundation-industry partnership that is developing neuroimaging tools as potential biomarkers for ALS progression; expanding the Northeast ALS Consortium (NEALS) biorepository; and supporting new phase IIA pilot clinical trials using biomarkers. Together, these projects will significantly advance the ability to identify and track key aspects of disease progression, and hence speed clinical trials.
Claimed to be the largest consortium of ALS clinical researchers in the world, the Northeast ALS Consortium (NEALS) is an international, independent, non-profit group of researchers who collaboratively conduct clinical research in ALS and other motor neuron diseases. The consortium’s mission is to translate scientific advances into new treatments for people with ALS and motor neuron disease as rapidly as possible.
The goal of biomarker discovery is to find changes in various measures through brain and spinal cord imaging or changes in muscle strength, blood, or cerebrospinal fluid (CSF) that predict disease or change as disease progresses as a result of a therapeutic intervention. JA biomarker is a measurable quantity that can be used to diagnose disease, track progression, or monitor response to therapy. Changes observed in the CSF could be used to indicate new therapeutic targets or in a clinical trial to track disease progression more rapidly as opposed to the current qualitative clinical measures used.
“Biomarkers that can determine risk, improve diagnosis, track disease progression and confirm drug engagement with the intended target are critical for accelerating the search for treatments,” says Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “As objective measurements of disease, biomarkers allow clinical trials to be smaller and shorter, enabling a more rapid evaluation of potential therapies.”
At The ALS Association, Dr. Bruijn leads a global ALS research effort, Translational Research to AdvanceTherapies for ALS (TREAT ALS) that funds research from early target identification to preclinical research and early pilot clinical trials. with the goal to move treatment options from “bench to beside.” She has made it a priority to collaborate with other funding agencies, in particular The National Institute of Health, The Department of Defense and many other not-for-profit ALS organizations, as well as other foundations focusing on neurodegenerative research. These collaborations ensure that increased dollars are spent on ALS research. Dr. Bruijn is involved in project development, encouraging partnerships with academe and biotech, and has played a key role in forging collaborations amongst investigators. An ALS Association release notes that it is her strong belief that only through collaboration among a wide range of disciplines will we be successful in changing the course of ALS and finding a cure.
Through participation at scientific meetings both nationally and internationally ALSA receives wide-spread recognition amongst the scientific community. Dr. Bruijn represents The ALS Association on several scientific and research committees world-wide and acts as advisor to scientists, government officials and industry leaders seeking council in the field of ALS research. She continues to publish in the field in peer-reviewed journals and remains actively engaged in understanding the most recent research developments.
The ALS Association release notes that in other areas of medicine, biomarkers have greatly accelerated discovery of new treatments, and that several efforts are already underway to identify and validate ALS-specific biomarkers — efforts that will be significantly enhanced by increased investment to improve sample collections with detailed clinical phenotyping and formation of initial foundation for the development of an ALS Biomarker Consortium.
The Biomarker Consortium is intended to include all interested and willing stakeholders that may participate with equal opportunity to contribute to the broader mission of biomarker development and validation with associated deep phenotyping. This organized structure is hoped to attract industry partners and funding opportunities from the National Institute of Neurological Disorders and Stroke (NINDS), and to build on experiences from the Michael J. Fox Foundation and NINDS.
Three new projects funded by The ALS Association are:
• Expansion of NEALS Biorepository at Barrow Neurological Institute, Phoenix AZ and Deep Phenotyping
Phoenix Children’s neurosciences department has formed an alliance with Barrow Neurological Institute, creating Barrow Neurological Institute at Phoenix Children’s Hospital, which offers comprehensive inpatient and outpatient neurological care and services to infants, children and teens with neurological-related problems, and one of the few hospitals to offer pediatric neurosurgery, neurology, psychology, psychiatry, developmental pediatrics and rehabilitation in one central location.
This project will carry out a longitudinal collection of blood and CSF from 150 people with ALS over the course of their disease. At the same time, detailed clinical measurements will be made of respiratory function, cognitive function, muscle strength, and other aspects of the disease. The fluids and clinical data are to be stored in the NEALS biorepository — a major site for storage, curation, and research on ALS biosamples — and be made available for biomarker discovery research. This project will be led by Jeremey Shefner, M.D., Ph.D., Robert Bowser, Ph.D., and Shafeeq Lahda, M.D., of Barrow Neurological Institute. This research project is also supported by a generous matching gift from Mary Lou and Ira Fulton.
• Biomarker Validation Study
This study will attempt to provide a validation of a proteomic signature of ALS in the CSF of 300 people with the disease. The release notes that recent research has indicated that the ratio of two CSF proteins, neurofilament heavy chain and complement C3, is altered in people with ALS, and this altered ratio may serve as a diagnostic biomarker. “The diagnosis of ALS is currently made using clinical measures that typically occur over multiple visits to a neuromuscular specialist,” notes Dr. Bruijn, “and typically takes up to one year from symptom onset. Earlier patient diagnosis would permit enrollment in clinical trials at an earlier stage of disease, which will help in the search for more effective drug treatments.”
The study is being undertaken by Andreas Jeromin, Ph.D., and Robert Bowser, Ph.D., of Iron Horse Diagnostics of Scottsdale, AZ, and is being co-funded by the National Institutes of Health. Iron Horse Diagnostics, a privately held molecular diagnostic company focused on the development and commercialization of novel tests to support the diagnosis and management of ALS, traumatic brain injury (TBI), and other neurological diseases. is developing markers of disease progression that will be useful to monitor disease progression and drug treatments during clinical trials, and has received funding from the ALS Association Biomarker Validation Study, which will build on previous results showing that the ratio provides 92 percent sensitivity and 94 percent specificity for presence of ALS. Iron Horse will further validate these tests and perform both a prospective clinical study and assay qualification within a commercially certified (CLIA) laboratory to commercialize the diagnostic tests. Validation of the biomarker would allow further development and, ultimately, the first commercially available clinical test for presence of ALS. Iron Horse is also developing the first diagnostic test for ALS that will rapidly determine if someone has the disease. More information on The ALS Association’s support of the CReATe Consortium (see below) and the biomarker development/validation request for applications, can be found at http://www.alsa.org/research/for-researchers/call-for-abstracts.html.
• Biosample Collection for CReATe
This collection will support the growth and expansion of a biorepository for a newly funded National Institute of Health Rare Diseases Clinical Research Consortium, the Clinical Research in ALS and Related Disorders for Therapeutic Development Consortium (CReATe) . CReATe will enroll patients with sporadic and familial forms of amyotrophic lateral sclerosis, frontotemporal dementia (FTD), primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and progressive muscular atrophy (PMA). The goals of the CReATe consortium are to advance therapeutic development for this group of neurodegenerative disorders through study of the relationship between clinical phenotype and underlying genotype, and also through the discovery and development of biomarkers.
CReATe will bring together biochemists, geneticists, clinicians, Pharma, and partner groups involved in patient education and advocacy including THE ALS Association, Muscular Dystrophy Association, ALS Recovery Fund, Association for Frontotemporal Degeneration, Spastic Paraplegia Foundation, PatientsLikeMe, and the National ALS Registry. Successful completion of the CReATe Consortium objectives will lay the necessary foundation for future trials in genetically homogeneous patient populations (including, for example, patients with C9orf72 repeat expansions), thereby advancing science towards development of effective therapies for patients afflicted with these devastating degenerative disorders. As part of this initiative The ALS Association will support the enhancement of a repository of biosamples collected longitudinally with deep phenotyping of approximately 700 people with ALS. This effort, led by Michael Benatar, M.D., Ph.D., of the University of Miami, will combine detailed clinical data with biosample analysis to search for biomarkers that correlate with clinical characteristics, including patterns of disease spread and the rate of disease progression. Funding by The ALS Association will allow more extensive samples to be collected, stored, and shared with the ALS research community.
The ALS Association
Northeast ALS Consortium
National Institute of Neurological Disorders and Stroke (NINDS)
Barrow Neurological Institute at Phoenix Children’s Hospital
Iron Horse Diagnostics
Clinical Research in ALS and Related Disorders for Therapeutic Development Consortium (CReATe)
The ALS Association
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