From October 6-7, 2021, researchers and stakeholders descended upon the virtual Northeast Amyotrophic Lateral Sclerosis Meeting to discuss new trends, research, and therapies within the field. According to ALS News Today, some data presented during the event centered around SBT-272, an investigational therapy for patients with amyotrophic lateral sclerosis (ALS). Within preclinical studies, researchers determined that, in mice models of ALS, SBT-272 helped protect mitochondrial health against toxic TDP-43 aggregates.

SBT-272

In the past, research has shown that TDP-43 sometimes plays a role in neurodegeneration. This protein has been linked to Alzheimer’s disease, progressive supranuclear palsy (PSP), Parkinson’s disease, and more.

Patients with ALS typically have smaller and lower-density mitochondria in primary motor neurons. Motor neuron damage is a key component of ALS. So when both motor neurons and mitochondria are impaired or damaged, patients experience a number of related health effects. In some patients, abnormal TDP-43 build-up also plays a role in disease progression.

Thus, Stealth Biotherapeutics developed SBT-272 to promote mitochondrial health and protect against damage. SBT-272 works by reducing oxidative stress and improving cellular energy production. Together, this helps prevent damage to and imbalance within the cell. SBT-272 targets cardiolipin on the mitochondrial inner membranes.

In preclinical studies, researchers found that:

• SBT-272 reduced oxidative stress in mice models of ALS.
• In mice models with TARDBP gene mutations, SBT-272 improved mitochondrial mobility and structure, helped regrow nerve fibers, and prevented structural defects within mitochondria.
• The investigational treatment is able to cross the blood-brain barrier, allowing for more targeted treatment.
• SBT-272 also improved life span and delayed symptom onset in mice models of ALS.
• In healthy volunteers, SBT-272 was seen to be both safe and well-tolerated.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by nerve cell death within the brain, brain stem, and spinal cord. ALS can be sporadic (accounting for 90-95% of diagnoses) or familial (inherited, accounting for 5-10% of diagnoses). While it can affect those of all ages and races, it most often occurs in white males between ages 60-69. Males are typically affected more often than females. In ALS, as nerve cells die, it inhibits communication with muscles, causing patients to lose voluntary movement and control. Symptoms include:

• Anxiety and depression (or other psychological stress)
• Frequent tripping or falling
• Difficulty with small movements or performing everyday tasks
• Slow or slurred speech
• Muscle weakness, often in the arms, legs, and hands
• Difficulty walking, speaking, and swallowing
• Muscle cramping or spasms
• Poor posture and balance
• Inability to move muscles across the body