OP-101 is a hydroxyl dendrimer conjugated through a disulfide bond to an anti-inflammatory drug creating a new chemical entity. Neuroinflammation is caused by oxidative stress in activated microglia and astrocytes. OP-101 selectively targets these cells and is internalized. Upon internalization, OP-101 releases the drug relieving the oxidative stress and reducing or eliminating the neuroinflammation. The hydroxyl dendrimer is then excreted intact in the urine.



The free drug is used at high systemic doses (140 mg/kg/day) up to 3 times per day before and after bone marrow transplant without toxicity in ccALD patients.  The effects of systemic (IV) free drug are limited due to the lack of targeting and limitations on dosing.  In animal studies, OP-101 has been shown to significantly reduce neuroinflammation and oxidative stress, reverse the progression of neonatal brain injury and improve motor function, in rabbits born after an in utero challenge with endotoxin.  A single dose of OP-101 safely restored function in rabbits with neonatal brain injury, and they matured to adulthood without visible signs of neurological impairment. In comparison to OP-101 treated animals, vehicle treated animals show a significant worsening of motor function and eventually die within ~10 days of birth.

Safe Selective Targeting of Neuroinflammation in Nonclinical Studies

  • OP-101 selectively targets to activated microglia in brain regions with neuroinflammatory-induced impairment of the blood-brain-barrier
  • OP-101 releases anti-inflammatory drug in the presence of intracellular levels of glutathione, which enables release specifically in the intracellular space
  • OP-101 improves neuropathological markers that increase due to neuroinflammation and are associated with neuroinflammatory conditions
  • OP-101 improves neurobehavioral symptoms caused by neuroinflammation in the animal models
  • OP-101 provides superior efficacy compared to free drug at 100-fold higher doses than OP-101 in animal models
  • Macrophages isolated from ccALD patients and stimulated with VLCFA have significantly reduced cytokine expression and glutamate secretion when treated ex vivo with OP-101 (see slides)
  • No adverse effects were observed in a pilot toxicology study of newborn rats administered up to 1000 mg/kg OP-101 every other day