Ampakines stimulate phrenic motor output after cervical spinal cord injury

Novel regenerative drug, SPG302 promotes functional recovery of diaphragm muscle activity after cervical spinal cord injury

“…A plethora of therapeutic approaches have been shown to improve the proportion of rats with recovered DIAm EMG following C 2 SH, including neurotrophic support, intermittent hypoxia and augmentation of glutamatergic or serotonergic receptor activation (Fuller et al., 2003; Gransee et al., 2013, 2015; Hernandez‐Torres et al., 2017; Mantilla, Gransee et al., 2013; Martinez‐Galvez et al., 2016; Sieck et al., 2021; Wollman et al., 2020; Zhou & Goshgarian, 1999). However, not all these approaches display even a modicum of the practicality of the daily systemic dosing used in the current study.…”

“…Earlier generations of pegylated benzothiazole derivatives were shown to increase post‐synaptic spine densities and functional synapses via an F‐actin cytoskeleton‐dependent mechanism (Cifelli et al., 2016; Lee et al., 2016; Zhang et al., 2019). While the effect of SPG302 and prototype compounds on spinal cord injury remains unknown, prior studies demonstrate the importance of glutamatergic receptors in improving recovery following C 2 SH (ElMallah et al., 2015; Gransee et al., 2017; Mantilla et al., 2012; Rana, Sieck et al., 2020; Wollman et al., 2020) and the presence of dendritic spines on spinal motor neurons (Bandaru et al., 2015; Fogarty, Mu et al., 2017, Fogarty et al, 2020b).…”

Acute ampakines increase voiding function and coordination in a rat model of SCI

“…The AMPA receptor can be allosterically modulated using pharmacologic compounds called ampakines (Arai and Kessler, 2007), and recent work suggests that these compounds have therapeutic value after SCI (Rana et al, 2021;Wollman et al, 2020).…”

“…For example, when given after acute or chronic SCI in rats, ampakines have a powerful, beneficial impact on the glutamatergic synaptic pathways, which control breathing (Rana et al, 2021;Wollman et al, 2020). After high cervical SCI, diaphragm output is diminished, but systemically providing a low dose of ampakine can cause a rapid and sustained increase in diaphragm electromyogram output (Rana et al, 2021).…”

“…The AMPA receptor can be allosterically modulated using pharmacologic compounds called ampakines (Arai and Kessler, 2007), and recent work suggests that these compounds have therapeutic value after SCI (Rana et al, 2021; Wollman et al, 2020). For example, when given after acute or chronic SCI in rats, ampakines have a powerful, beneficial impact on the glutamatergic synaptic pathways, which control breathing (Rana et al, 2021; Wollman et al, 2020). After high cervical SCI, diaphragm output is diminished, but systemically providing a low dose of ampakine can cause a rapid and sustained increase in diaphragm electromyogram output (Rana et al, 2021).…”