Accelerating identification of cross-species suppressor genes and elucidating early pathophysiology in ALS Research Summary Generate animal models and human cell models that will more accurately parallel familial ALS (fALS).  The team will harness strengths of four powerful model systems (worms, flies, mice, human iPSCs) to develop a robust understanding of what goes awry in ALS neurons, while also identifying conserved, cross-species suppressor genes whose perturbation could stop ALS. Investigators Brown University Justin Fallon Anne Hart Diane Lipscombe Robert Reenan Kristi Wharton Massachusetts General Hospital Brian Wainger University of Massachusetts Medical School Robert Brown D.Phil., MD [...]

SPINE ALS Research Summary The goal of this project is to measure spinal cord inflammation using [11C]PBR28-PET in 10 people with ALS compared to 5 healthy volunteers. Positron emission tomography (PET) is a technology that allows accurate measurement of certain proteins or metabolites in living people. We are using a PET tracer (contrast) called PBR28 that binds to active inflammatory cells and allows us to measure and localize brain inflammation. We were able to demonstrate increased inflammation in the areas that control voluntary muscle movements (e.g., motor cortex) in people with ALS. Zucher N, Lawson R, Loggia M, Chonde DB, [...]

Research Summary Only a small percentage of patients with ALS participate in clinical trials. A major reason is that trials are conducted in a limited number of academic medical centers, and that in-person visits are required on a frequent basis. At these visits, trial outcome measures are obtained, with trained evaluators performing these measures. Our study will test the hypothesis that ALS patients can perform clinically meaningful outcome assessments at home, thus obviating a major need to come to the study center. We will provide simple tools for assessment, train subjects via webinars, and patients will enter their data to [...]

Nonclinical Safety Evaluation of AMX0035 to Support Translation to Clinical Trials Research Summary Principal Investigators: Joshua Cohen & Justin Klee Neurodegeneration and neurotoxic inflammation are hallmarks of ALS and together form a vicious cycle that is one of the key drivers of functional decline in patients. Our lead candidate, AMX0035, is a proprietary combination of two compounds that is designed to break this cycle, thereby halting clinical progression. Based on strong in-vitro and in-vivo results, we now seek to evaluate our promising therapeutic in patients with ALS. Nonclinical safety studies, also called toxicology studies, are the essential FDA-required battery of tests needed to translate [...]

MAP (Microbiome Assessment Project) in ALS Research Summary There is growing interest in how the interplay between the intestinal microbiota (i.e., bacteria in the gut) and its host influence the onset and course of neurodegenerative diseases, potentially mediated by immune mechanisms which modulate the microglial environment. No studies have previously examined whether the overall composition of the intestinal microbiota, or specific bacterial species, are associated with ALS. In this pilot study, the intestinal microbiota of 100 people with ALS and 100 healthy controls will be compared. The role of this project is to develop preliminary data as to whether the [...]

ALERT (ALS Early Recognition Timeline) Project Research Summary People with ALS often seek evaluation from multiple providers prior to diagnosis, with an average time from symptom onset to diagnosis of 11.5 months. The goal of this study is to accelerate ALS diagnosis by developing a natural language processing-based algorithm to identify people at risk for ALS and a scale to help physicians identify people with ALS at early stages of the disease. We aim to scale up these early ALS diagnostic tools for use in many US hospitals, with the ultimate goal to identify and treat people with ALS early [...]

NeuroBANK™ as an Accelerated Clinical Research Environment: Development, Deployment and Services to ALS Research Community Research Summary Principle Investigators: Merit Cudkowicz MD & Alex Sherman Successful implementation of NeuroBANK™ will allow for a standardized patient-centric approach to clinical research in ALS with information linked across studies, locations and modalities. Standard Common Data Elements, standard operating procedures and GUID technology will lead to accelerated studies' review, approval, deployment and patient enrollment. NeuroBANK™ is a patient-centric clinical research platform that allows capture and aggregation of clinical and clinical research data from simultaneously running research projects and links these data with biospecimen repositories, [...]

Imaging Axonal Transport Research Summary Principle Investigator: Robert Brown D.Phil., MD The field of ALS needs a tool, often called a biomarker, by which the activity of this disease can be gauged. This is potentially important not only for diagnosing the disease, but also for identifying factors causing ALS and for gauging the efficacy of putative ALS treatments. One such biomarker is to quantify a parameter that directly reflects the health of the motor neuron. One property that is promising in this regard is axonal transport, the process by which a nerve cell moves cargoes such as proteins and organelles up [...]

Application of MultiOmyx to iPSC Models of ALS Research Summary Principle Investigator: Clive Svendsen PhD Induced pluripotent stem cell technology (iPSC) holds great promise for accelerating our understanding of the molecular mechanisms and pathways leading to motor neuron degeneration in ALS. In vitro cellular model systems generated from patient-derived iPSC lines can recapitulate many aspects of in vivo cellular pathology, and beyond basic disease research may serve as a powerful test bed to screen potential therapies. Therapeutic screening on iPSC-derived models will likely be complementary to, and in some aspects superior to other approaches, including animal models in terms of [...]

Using Novel Imaging Agents as a Biomarker for ALS Progression in the fALS RAT Research Summary Principle Investigator: Clive Svendsen PhD Assessing the progression of ALS in both animal models and the human condition would provide the ideal biomarker for testing novel compounds rapidly and efficiently. However, while MRI and other imaging modalities exist, they have not been fine-tuned for this neurological condition. Our rationale is that through better imaging of disease progression in ALS within individual patients, drug therapy throughput and success will be increased. The novel imaging marker project is in collaboration with GE and asks whether a [...]