Additional Table 1.
Therapeutic approaches for modulation of p75 neurotrophin receptor signaling
| Therapeutic entity | Therapeutic strategy and effects |
|---|---|
| LM11A-31 | • Small molecule that binds p75NTR • Bioavailable, with excellent CNS penetration • Neuroprotective and anti-inflammatory effects in animal models of neurodegenerative disease, injury, and infection • Completing phase 2a in participants with mild to moderate Alzheimer’s Disease |
| p75ECD-Fc, AAV-p75ECD | • p75NTR cleavage product, engineered for improved tissue delivery • Neuroprotective and anti-inflammatory effects in animal models of Alzheimer’s disease, frontotemporal lobar degeneration, and depression • Effective delivery to the CNS |
| TAT-Pep5 | • Small peptide conjugated to the HIV tat protein for improved tissue penetration • Blocks interaction of p75NTR with cytoskeletal regulatory factor, Rho-GTP • Neuroprotective and anti-inflammatory in animal models of TBI and subarachnoid hemorrhage |
| p75 siRNA | • Knockdown of p75NTR expression • Neuroprotective in an animal model of TBI |
| p75 neutralizing antibody | • Antibody to p75NTR • Evidence for neuroprotection after bulbectomy, attenuates photoreceptor degeneration and microglial activation |
| THX-B | • Small molecule p75NTR antagonist • Protects against diabetic retinopathy, voiding dysfunction, photoreceptor degeneration and retinitis pigmentosa in various animal models |
| EVY 901 | • Small molecule that inhibits p75NTR dimerization • Neuroprotective and anti-inflammatory in an animal model of TBI • Reduces expansion of monocytes in response to LPS |
| PD90780 | • Small molecule that interacts with NGF to prevent binding to p75NTR • Reduces cystitis-induced bladder dysfunction in a rat model |
This Additional Table highlights various therapeutic approaches designed to modulate the activity of the p75 neurotrophin receptor. The summary specifically highlights in vivo studies representative of a growing area of research and is not intended to be comprehensive. AAV: Adeno associated virus; CNS: central nervous system; ECD: extracellular domain; Fc: complement binding fragment of IgG; LPS: lipopolysaccharide; siRNA: small inhibitory ribonucleic acid; TBI: traumatic brain injury.