PTX BD4-3 / PharmatrophiX - LARVOL DELTA

A SMALL MOLECULE TRKB AGONIST ENHANCES RESILIENCE TO OLIGOMERIC AΒ AND TAU-INDUCED SPINE LOSS AND RESTORES TRKB-AKT SIGNALING (ADPD 2026) - "Two cohorts, at ages 5 and 12 months, were treated intraperitoneally with PTX-BD4-3 or vehicle for 3 months, then synaptic proteins, dendritic spines, and TrkB signaling were assessed... Small molecule TrkB agonists have a broad range of effects, promoting synaptic resilience and restoring TrkB signaling. Such compounds may hold potential as AD therapeutics."

Alzheimer's Disease • CNS Disorders • SYP

A small molecule TrkB receptor agonist reduces thalamic damage following cortical ischemic stroke (Neuroscience 2024) - "Furthermore, given that BDNF-TrkB signaling has been shown to inhibit microglial activation by previous studies, we investigated whether a small molecule TrkB-receptor partial agonist PTX BD4-3 (BD) can rescue the post-stroke thalamic damage by inhibiting microglia activation and A1 astrocyte formation...Results indicated that BD treatment decreased microgliosis, the levels of c1q, IL-1α, and TNFα, number of neurotoxic A1 astrocytes, as well as neuron loss in the affected thalamic regions. In summary, our findings suggest that systemic partial TrkB receptor agonist treatment could be a potential strategy to reduce neuroinflammation and neuronal damage in the thalamus after cortical stroke."

CNS Disorders • TNFA

Partial Agonist Activation of Trkb-r Prevents Interneuronal Abnormalities Following Neocortical Status Epilepticus (AES 2022) - "We hypothesized that a single episode of FSE induces abnormalities in inhibitory neurons and inhibitory synaptic connectivity and that treatment with a partial agonist of TrkB-Rs: PTX BD4-3 (BD, Adams et al., 2020) would rescue the observed abnormalities. We induced a single episode of FSE by epidural application of gabazine and 4-AP (150µM) over the right somatosensory cortex of anesthetized mice (Perez-Ramirez et al., 2020)...After ~2hr, seizures were terminated with an i.p. injection of diazepam (5-10 mg/kg)...Local field potential recordings were used to determine whether BD treatment, compared to vehicle, decreased the incidence of epileptiform activity in vitro. Statistical significance was tested with Wilcoxon test (p < 0.05)."

Anesthesia • CNS Disorders • Epilepsy • BDNF • NTRK2

TrkB Receptor Activation Reduces Neuroinflammation and Thalamic Injury Following Stroke (AES 2021) - "Rats were treated for 7 days beginning the day of stroke with ip injections of saline or PTX BD4-3 (BD), a small molecule partial agonist of the BDNF TrkB receptor that has been shown to achieve functional brain levels following peripheral administration. 1) There was significant neuron loss in thalamic nRT, VPL, and VPM nuclei (nRT: 140 ± 4.52 vs 68.09 ± 4.35, p< 0.001; VPL+VPM: 38.86 ± 2.60 vs 13.08 ± 2.40, p< 0.001), accompanied by microgliosis, astrogliosis (GFAP-IR in VPL+VPM: 7.73 ± 1.27 vs 23.70 ± 1.50 pixels, p< 0.001), reactive neurotoxic A1 astrocytes, and upregulated TNFα; 2) BD compared to saline treatment decreased microgliosis, astrogliosis (GFAP-IR in VPL+VPM: 23.70 ± 1.50 vs 6.713 ± 0.58 pixels, p< 0,001), the number of A1 astrocytes (nRT: 42.89 ± 3.18 vs 10.25 ± 1.25, p< 0.001; VPL+VPM: 94.33 ± 10.03 vs 25.25 ± 8.14, p< 0.01), and the level of TNFα, as well as neuron loss..."

Anesthesia • Cardiovascular • CNS Disorders • Epilepsy • Immunology • Inflammation • Ischemic stroke • Vascular Neurology • GFAP • NTRK2 • TNFA