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A hallmark feature of ALS, thought to occur even before symptoms appear, is the overexcitement (or hyperexcitability) of motor neurons in the brain. This change occurs at the cellular level and cannot be noticed by those who experience it, but researchers have found evidence of hyperexcitability in both electrical recordings from the brain and markers in the cerebrospinal fluid of people with ALS. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that uses a magnetic field to stimulate and modulate the excitability of nerve cells. One method, known as continuous theta burst stimulation (cTBS), is believed to safely reduce this hyperexcitability by delivering a high number of magnetic pulses to a targeted area of the brain in a short period of time. In this pilot study, 15 participants will undergo the procedure over 5 days. Researchers will monitor participants to ensure the technique is safe and well-tolerated and assess any changes in corticospinal excitability and biological markers at one week and three weeks after the treatment.

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.

Ibudilast (also referred to as MN-166) is an experimental therapy being developed to treat ALS. This broad target drug is thought to reduce the activity of immune cells in the brain, thereby supressing inflammation. It is also believed to promote the production of neurotrophic factors which play a role in the growth and survival of motor neurons. The Phase 2b/3 COMBAT-ALS clinical trial will enroll 230 participants living with ALS and last 12 months. Researchers will monitor participants to ensure that the drug is safe. Researchers will also evaluate the impact of ibudilast on the progression of ALS by evaluating changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) score, as well as muscle strength, quality of life, and respiratory function. Ibudilast will be taken by mouth in combination with a dose of riluzole. Researchers believe the anti-inflammatory and neuroprotective characteristics of ibudilast make it a promising treatment option for ALS.

To learn more, please click here to view a webinar hosted by the study sponsor, MediciNova.

Biomarkers that can effectively measure neurodegeneration are much needed and essential to understanding, diagnosing, and ultimately treating ALS. In this observational study, researchers are seeking to identify and measure the levels of specific biomarkers in ALS patients being treated with edaravone (Radicava). The biomarkers of interest are linked to oxidative stress, inflammation, and neuronal and muscle injury. The study will enroll approximately 300 participants who will be followed over a 24-week period. Biological samples (blood and urine) will be collected from study participants for analyses. Participants can also opt in to receive their genetic results for five common mutations associated with ALS, including SOD1, TARDBP, C9ORF72, FUS and VCP.

Antibodies are proteins that are produced by the immune system to protect the body against foreign invaders like bacteria and viruses, and work by binding to specific proteins on the harmful agents and triggering their removal and/or destruction. In this Phase 2 clinical trial, researchers will be testing the safety of a human antibody (called AP-101) designed to target an ALS-linked protein called SOD1. Evidence suggests that the misfolding of SOD1 in cells can cause the protein to take on a toxic gain of function. Researchers are hopeful that targeting this protein may represent a promising strategy for the treatment of ALS. A previous Phase 1 study found the drug to be safe and well-tolerated at the tested doses. In this follow-up study, researchers expect to enroll 63 participants who will be randomly divided to either receive the active drug (AP-101) or placebo intravenously (IV), for 48 weeks. Both individuals with familial, SOD1-ALS and sporadic disease will be eligible to participate. Researchers will monitor participants to ensure that the drug is safe, identify any side effects, determine the appropriate dosage, and learn more about how the body breaks down the drug internally.

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.

Withania somnifera is a herb whose extracts have been in use for centuries in Indian, Chinese and Arabic traditional medicines. Extracts were reported to have anti-inflammatory, antitumor, anti-stress, antioxidant, immunomodulatory, and rejuvenating properties. There is a growing body of evidence suggesting that Withania somnifera extract may also have neuroprotective effects. In previous studies using mouse models of ALS (1,2), researchers found that treatment with Withania somnifera increased lifespan and improved motor performance. The positive effects observed were thought to be due, in part, to Withania somnifera’s anti-inflammatory properties as evidenced by reduced activation of NF-κB, which plays a key role in regulating the immune response. This Phase 2 clinical trial is expected to enroll 75 participants, who will be given Withania somnifera extract, or placebo, by mouth over an 8-week period. Researchers will monitor participants to ensure that the drug is safe and determine the appropriate dosage