Treg Study: Therapeutic Goal – To Increase Neuroprotective FoxP3 Tregs in ALS Patients Research Summary Principle Investigator: Stanley Appel MD This study may lead to Treg cell therapy for symptom management or potential slowing of disease progression in ALS and related disorders. This study is to isolate T regulatory (Treg) cells from the blood using leukapheresis, and expand T regulatory (Treg) cells in the laboratory in up to twelve patients with ALS. Leukapheresis is a laboratory procedure in which white blood cells are separated from a sample of blood. Once separated, the remainder of the blood is returned to the [...]

 Development of AAV-Mediated SOD1 Gene Silencing Therapy in ALS Research Summary Principle Investigators: Robert Brown D.Phil., MD & Merit Cudkowicz MD About 10% of ALS cases are familial. Most of the known genetic defects in familial ALS act by triggering one or more toxic processes that impair the viability of motor neurons, leading to motor neuron death. This project will use viruses to introduce reagents into the brain and spinal cord that block the mutant genes from triggering toxicity. This is accomplished by turning off the activity of those genes using new technologies for so-called “gene silencing.” The viruses are used [...]

Silencing of ALS-Causing Mutant Genes Research Summary Principle Investigators: Robert Brown D.Phil., MD & Merit Cudkowicz MD About 10% of cases of ALS run in families and are caused by mutant genes, including the first-identified ALS gene known as superoxide dismutase 1 (SOD1). In most cases, the mutant genes make a mutant, toxic gene product, which in the case of SOD1 is a protein with a propensity to misfold. Data also argue that non-mutant forms of these proteins may also play a role in non-familial ALS. Several lines of study indicate that when SOD1 is implicated in ALS, the goal is [...]

DIALS (Dominant Inherited ALS) Network Research Summary Research Summary While evidence of a pre-symptomatic period has emerged for a number of neurodegenerative diseases, a similar precursor period prior to symptom development in ALS has yet to be defined, and pre-symptomatic biomarkers of ALS have yet to be discovered. As a result, researchers are unable to target people in the very earliest stages of ALS, when neurodegeneration is most nascent and may be most easily modified or halted. Current barriers to genetic testing in asymptomatic family members of people with ALS include insurance eligibility and cost. By using a funded research [...]

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 [...]