Deep Phenotyping

• ALS and related disorders are characterized by complex phenotypes that are an amalgam of upper and lower motor neuron degeneration and frontotemporal spectrum dysfunction.
• Understanding the nuances of these phenotypes (for example, the onset and evolution of motor, cognitive and behavioral manifestations) through detailed assessments – i.e. “deep phenotyping” – is critical to therapeutic development.
• We study individuals with ALS or a related disorder (e.g. ALS-FTD, MSP, PMA, PLS, HSP); those at elevated genetic risk for ALS; as well as healthy controls.

Causes & Modifiers

• Genetic makeup (genotype), environmental exposures, and advancing age are the three most important risk factors for ALS. In some patients, a single gene mutation may be responsible for causing disease. In many others, we suspect that disease results from a complex interplay between genes, environment, and age.
• In collaboration with colleagues who study ALS genetics/genomics and environmental exposures, we seek to identify the cause(s) of ALS (and related disorders); to identify modifiers of the clinical phenotype; and to explore gene x environment interactions.

Biomarker Discovery & Validation

• Biomarkers are quantifiable biological markers of disease. The appropriate use of biomarkers could greatly aid therapy development.
• Importantly, before its use in a clinical trial, a biomarker must first be clinically validated to be “fit for purpose”. (For example, EMG, as a biomarker, is suitable for diagnosing ALS, but not for predicting prognosis or measuring treatment response.)
• We focus on both biomarker discovery and validation, with particular interest in biochemical markers in biofluids (e.g. blood, urine, spinal fluid); imaging (e.g. MRI) markers; and both electrical and physiological measures of nerve and muscle function.

Novel Data Collection Methods

• Traditionally, research data are collected during in-person visits to a research center. This approach, though the gold standard, places a heavy burden on study participants as well as research teams.
• We have long championed the value—and demonstrated the feasibility—of using remote assessments (e.g. home spirometry) to collect research data when in-person visits to study site are not feasible. This approach has become especially relevant given the COVID-19 pandemic.
• We have also developed approaches to explore whether electronic health record (EHR) data, collected at the point of care in multidisciplinary ALS clinics, might be used for research purposes and to improve the quality of care.

Disease Biology & Drug Discovery

• The single greatest challenge to effective therapy development for ALS (and related disorders) is our lack of understanding of the underlying causes and mechanisms of disease.
• Through collaborative work with Dr. Zane Zeier and others, we are using induced pluripotent stem cells (iPSCs), as well as motor neurons and brain organoids derived from iPCSs, to investigate the underlying biology of disease and to conduct pre-clinical drug screening.
• Benatar has been at the forefront of championing the need for greater methodological rigor in pre-clinical therapeutic studies, which is critical to the success of translating promising therapeutics in animal models of ALS, into meaningful therapies for patients with ALS.

Clinical Trials

• Clinical trials, or interventional studies, are essential for determining whether a new experimental treatment is effective, harmful, or inert (i.e. safe but not effective).
• We have been at the forefront of promoting innovative ALS trial designs that use, for example, enrichment strategies to facilitate detection of therapeutic effect.
• We also participate in multi-center trials of promising agents, and we are leading the effort to discover opportunities to prevent (or delay the onset of) ALS, at least among those at genetic risk for disease.

Please make your check payable to “University of Miami ALS Research Fund” and send it to the address below. If this is a gift in memory, or in honor, of someone special, please let us know.

ALS Research Fund
(c/o Dr. Michael Benatar)
University of Miami, Department of Neurology
1120 NW 14th Street, Room 1318
Miami, FL 33136