Drug Pipeline

The UPR is a stress response mechanism related to the endoplasmic reticulum. The ER is an organelle that participates in protein manufacturing and transport. In response to mis- or unfolded protein the UPR can slow production of new protein and “turn-up” pathways that process (fold) existing nascent protein.

Oxidative stress is an imbalance between the production of reactive oxygen species and the ability to detoxify them or to repair the resulting damage. Numerous studies have found evidence of increased oxidative stress in ALS pathogenesis.

The endothelium is a thin layer of cells that line the interior surface of blood vessels. The Blood Brain Barrier is composed of specialized endothelial cells and astrocytes that tightly control passage in and out of the CNS. Recent studies have shown a loss of endothelial integrity in the spinal cords of ALS patients.

Many researchers and clinicians suspect that the immune system plays a role in the pathophysiology of ALS. Modulation of immune related properties may be efficacious in ALS.

Oligodendrocytes and Shwann cells create a myelin layer around the axons of neurons in the central nervous system (CNS) and peripheral nervous system (PNS) respectively. Various strategies for protecting the myelin sheath and promoting remyelination may be protective in ALS.

Aberrent protein aggregates have been observed in ALS and other neurodegenerative diseases. Autophagy and proteasomal function are normal processes in healthy cells in which cells break down their own components for recycling or disposal. These processes may be influenced by therapeutics to reduce accumulation of protein in stressed neurons.

Trophins are proteins that have been shown through in vitro or in vivo systems to help neurons survive, differentiate, or grow. Trophins are being tested at TDI for therapeutic benefit.

The neuromuscular junction (NMJ) is the interface between a motor neuron and a muscle cell. Disruption of the NMJ is one of the earliest detected events in ALS models. Strategies aimed at maintaining or remodeling NMJs may be protective in ALS.

Pathology associated with proteins that normally assist in RNA processing and mutations in the genes that encode them have been associated with ALS and frontotemporal dementia. Therapeutics aimed at influencing RNA binding and metabolism may stabilize susceptible neurons.