Massachusetts General Hospital
Merit Cudkowicz MD
James Berry MD

Houston Methodist Neurological Institute
Stanley Appel MD

Massachusetts General Hospital
Merit Cudkowicz MD
James Berry MD

University of Massachusetts Medical School
Robert Brown D.Phil., MD

Massachusetts General Hospital
Merit Cudkowicz MD
James Berry MD

University of Massachusetts Medical School
Robert Brown D.Phil., MD
Chris Mueller PHD
Guangping Gao PHD

Katherine Nicholson MD
Timothy Miller MD, PhD
James Berry MD

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

Massachusetts General Hospital
Nazem Atassi MD

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 an online portal. For a sample of participating patients, we will compare AT HOME measures with those obtained at regular study visits by trained evaluators. We will also assess the extent to which frequent sampling of measures can reduce the variability of measurement; we expect that such sampling will increase reliability of measurement and potentially reduce the sample size required to see meaningful changes in response to experimental therapies.

Barrow Neurological Institute
Jeremy Shefner MD, PhD

Harvard Medical School
Seward Rutkove

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 a therapy from the lab to the clinic. We met with the FDA in a pre-IND meeting and received consent that our safety program would be sufficient to support our first clinical trial. As of September 16, 2015, we are approximately halfway through these safety studies, and have completed:

1)     The Ames Test

2)     Evaluation of Maximum Tolerated Dose in Rat and Mini-pig

3)     Dose Range Finding in Rat (mini-pig is currently underway)

4)     Development of Bioanalytical Methods

Following completion of our nonclinical safety program in early 2016, we will file an IND with the FDA to run a first-in-human clinical trial. We are very grateful to ALS Finding a Cure for their support for these pivotal studies that will bring AMX0035 to patients in need.

http://www.fiercebiotech.com/biotech/als-upstart-amylyx-gains-3m-grant-to-start-combo-trial

http://www.prnewswire.com/news-releases/the-als-association-and-als-finding-a-cure-announce-joint-funding-support-for-amylyx-clinical-trial-of-amx0035-for-the-treatment-of-als-300300955.html

http://www.businesswire.com/news/home/20160822005017/en/Amylyx-Announces-5-Million-Series-Financing-Support

Amylyx Pharmaceuticals
Joshua Cohen
Justin Klee

Gad Consulting Services
Shayne Gad PhD
Dexter Sullivan MS

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 intestinal microbiota is associated with ALS risk or progression rate and is involved in ALS etiology. This study will use novel technology and is a collaboration project among the Harvard School of Public Health, Broad Institute, and the Neurological Clinical Research Institute at Massachusetts General Hospital, involving leading epidemiologists, microbiome analysts, and ALS clinical researchers. This project is co-funded by ALS Finding a Cure and a private donor.

Katherine Nicholson MD
James Berry MD
Alberto Ascherio

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 in the disease when chances of drug success are higher. This project is co-funded by ALS Finding a Cure and Biogen.

Katherine Nicholson MD
Nazem Atassi MD