The ability to accurately measure people’s brain degeneration may help researchers to find much needed biomarkers that are essential to understanding, diagnosing and ultimately treating ALS. Using advanced brain imaging techniques (magnetic resonance imaging, or MRI), this observational study will monitor over time the degree of change that occurs in the brains of people who are living with ALS. Each study participant will have 3 MRI scans over a period of 8 months, along with neurological and cognitive evaluations. This study is led Dr. Sanjay Kalra and will operate within the Canadian ALS Neuroimaging Consortium (CALSNIC), a cross-Canada imaging network funded by the largest-ever grant provided by the ALS Canada research program.
BIIB067 (also referred to as tofersen) is an antisense oligonucleotide (ASO) that is being studied to treat a familial form of ALS linked to mutations in the SOD1 gene. As a result of mutation, SOD1 is believed to gain a toxic function that is damaging to the nerve cells that control voluntary muscles, called motor neurons. Tofersen is designed to decrease production of SOD1 which researchers hope will lead to preservation of motor neurons and slowed progression of the disease. It is delivered into the spinal fluid through a procedure known as an intrathecal injection. Although a previous Phase 3 clinical trial studying tofersen was not able to demonstrate a statistically significant difference in ALSFRS-R score between the active drug and placebo groups over the 6-month study period, treatment with tofersen did show signs of clinical effect across multiple measures. This Phase 3 clinical trial, called ATLAS, is the first of its kind as it will be enrolling participants with a SOD1 mutation who are considered to be presymptomatic (e.g., do not yet show overt signs of the disease), but have an elevated biomarker indicating the sub-clinical triggering of ALS. The goal of this study is to determine whether presymptomatic treatment with tofersen can delay the onset of clinical ALS diagnosis and slow functional decline thereafter. Participants in the study will be treated for up to two years.
Abnormalities in a protein called TDP-43 are present in approximately 97 percent of all ALS cases. Preclinical studies have shown that when the amount of functional TDP-43 is decreased within cells, the level of another protein, STMN2, is substantially decreased. Patient tissues analyzed by researchers also showed that STMN2 levels are lower than expected specifically in motor neurons. These findings support the idea that a reduction in STMN2 resulting from TDP-43 dysfunction contributes to ALS and suggest that methods to preserve the levels of STMN2 within motor neurons may have a therapeutic benefit. QRL-201 is a genetically targeted therapy that aims to restore normal STMN2 levels in people living with ALS. This Phase 1 study will enroll 64 participants who will be randomly assigned to have either the active drug (QRL-201) or placebo delivered into the spinal fluid through a procedure known as an intrathecal injection. Researchers will monitor participants to ensure that the drug is safe, determine the appropriate dosage, and learn more about how the body breaks down the drug internally.