Recently Biogen announced two new clinical research projects in ALS. One of these is a clinical trial exploring a potential investigational therapeutic (BIIB067/ISIS-SODRX) for the SOD1 form of the disease, and the other will explore potential outcome measures for future use in all ALS clinical trials. Both trials are expected to open for recruitment soon at centers in the US and abroad. 

The investigational therapeutic clinical trial in ALS seeks to determine the safety and tolerability of an antisense oligonucleotide (ASO) therapy in people with ALS whom are also carriers of a mutation in the SOD1 gene. This trial builds on previous work using ASO technology to target ALS and is being conducted in partnership with Isis Pharmaceuticals, a San Diego biotechnology company. Isis officially announced the start of the trial December 11, 2015 with a press release.

The investigational therapeutic is designed to disrupt the process by which the mutated SOD1 gene creates misfolded proteins. These abnormal proteins and several different genes associated with ALS have been found to produce similar products. Misfolded proteins cause cells such as motor neurons significant cell stress. An abundance of misfolded proteins inside motor neurons is thought to play a central role in the onset and progression of ALS. This new clinical trial aims to halt the production of these misfolded proteins in hope of slowing or stopping the disease altogether. The investigational therapy will be delivered intrathecally to the spinal fluid. People with ALS enrolled in this trial will be asked to provide samples of their spinal fluid (cerebrospinal fluid, CSF) throughout the study which will allow the researchers to measure changes in the levels of SOD-1 as a result of treatment. This initial study is designed to determine the safety and tolerability of the ASO treatment, an important first step before moving into efficacy studies.

This new Phase 1 study builds on previous work led by Timothy Miller, Ph.D., M.D., using first generation ASO technology. This new trial will enroll more people with ALS than the previous study, and the ASO being evaluated has been improved upon. For example, the Generation 2.0 ASO has been redesigned to better target the precursors to misfolded SOD1 protein and to be delivered in a matter of minutes to the study participants, as opposed to many hours with the earlier generation of therapy.

The study is officially called “Single and Multiple Dose Study of BIIB067 (Isis-SOD1Rx) in Adults With Amyotrophic Lateral Sclerosis (ALS).Biogen and Isis Pharmaceuticals have organized a network of 18 enrollment centers in 9 countries to enroll as many as 72 people with ALS in the project. This is a two-part study in which testing positive for the SOD1 gene is NOT a requirement to participate in the initial part of the trial. More information about full inclusion criteria can be found online here.

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