Neuro-Repair Advanced

Archival Status

The Neuro-Repair Advanced protocol combines Dihexa and ARA-290 to address neurological repair at two distinct levels: synaptic plasticity and hippocampal neurogenesis (Dihexa) and peripheral nerve fiber regeneration with central neuroprotection (ARA-290). Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a small molecule peptide derived from angiotensin IV, developed at Washington State University. Its primary mechanism is potentiation of HGF/Met (hepatocyte growth factor/c-Met) receptor signaling — a pathway critical for long-term potentiation (LTP), the cellular basis of memory formation. Research at WSU demonstrated that Dihexa is approximately 10 million times more potent than BDNF at increasing synaptogenesis in hippocampal neurons in vitro. Animal studies show significant improvement in spatial memory and cognitive performance in models of Alzheimer's disease, TBI-induced cognitive impairment, and age-related cognitive decline. Dihexa exhibits extremely high oral bioavailability and central nervous system penetration, crossing the blood-brain barrier efficiently due to its lipophilic structure. ARA-290 is a non-erythropoietic peptide analogue of erythropoietin (EPO) that selectively activates the innate repair receptor (IRR) — a heterodimer of the EPO receptor and the beta common receptor (bCR) expressed on neural tissues, immune cells, and peripheral neurons. Unlike therapeutic EPO, ARA-290 does not stimulate red blood cell production, making it suitable for neurological research without hematological risk. Clinical Phase 2 trial data (Sarcoidosis patients with small nerve fiber neuropathy) showed significant improvements in corneal nerve fiber density, intraepidermal nerve fiber density, and neuropathic pain scores. ARA-290's mechanisms include: promotion of Schwann cell survival, axonal outgrowth, remyelination, and central neuroprotection via Akt and STAT3 signaling. The synergy between Dihexa and ARA-290 addresses neurological repair at complementary levels: Dihexa targets central synaptic plasticity and hippocampal neurogenesis, while ARA-290 addresses peripheral nerve fiber regeneration and provides central neuroprotection. Research applications include small nerve fiber neuropathy, TBI cognitive sequelae, diabetic neuropathy, and early-stage neurodegenerative disease.