Delving into the Latest Updates on APB-103 with Synapse

Overview

Basic Info

Drug Type

Gene therapy

Synonyms-

Target-

Mechanism-

Therapeutic Areas

Congenital DisordersDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

Alpha 1-Antitrypsin Deficiency

Inactive Indication-

Originator Organization

Apic Bio, Inc.Startup

Active Organization

Apic Bio, Inc.Startup

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

PURPOSETo determine retinal pathway origins of pattern electroretinogram (PERG) in macaque monkeys using pharmacologic dissections, uniform-field flashes, and PERG simulations.METHODSTransient (2 Hz, 4 reversals/s) and steady state (8.3 Hz, 16.6 reversals/s) PERGs and uniform-field ERGs were recorded before and after intravitreal injections of L-AP4 (not APB) (2-amino-4-phosphonobutyric acid, 1.6-2.0 mM), to prevent ON pathway responses; PDA (cis-2,3-piperidinedicarboxylic acid, 3.3-3.8 mM), to block activity of hyperpolarizing second- and all third-order retinal neurons; and TTX (tetrodotoxin, 6 μM), to block Na+-dependent spiking. PERGs were also recorded from macaques with advanced unilateral experimental glaucoma, and were simulated by averaging ON and OFF responses to uniform-field flashes.RESULTSFor 2-Hz stimulation, L-AP4 reduced both negative- and positive-going (N95 and P50) amplitudes in transient PERGs, and their counterparts, N2 and P1 in simulations, to half-amplitude. PDA eliminated N95 and N2, but increased P50 and P1 amplitudes, in that it enhanced b-waves. As previously reported, severe experimental glaucoma or TTX eliminated photopic negative responses, N95, and N2; glaucoma eliminated P50 and reduced P1 amplitude; TTX reduced P50 and hardly altered P1. For 8.3-Hz stimulation, L-AP4 eliminated the steady state PERG and reduced simulated PERG amplitude, whereas PDA enhanced both responses. TTX reduced PERG amplitude to less than half; simulations were less reduced. Blockade of all postreceptoral activity eliminated transient and steady state PERGs, but left small residual P1 in simulations.CONCLUSIONSTransient PERG receives nearly equal amplitude contributions from ON and OFF pathways. N95 reflects spiking activity of ganglion cells; P50 reflects nonspiking activity as well. Steady state PERG, in contrast, reflects mainly spike-related ON pathway activity.

100 Deals associated with APB-103

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