Therapeutics: Adenosine A1 receptor (ADORA1)
Mouse studies suggest an ADORA1 antagonist conjugated to gold nanoparticles could help treat respiratory paralysis in spinal cord injury (SCI) patients with less toxicity than the free antagonist. The conjugate consisted of mercaptosuccinic acid-capped gold nanoparticles linked to a CNS-toxic ADORA1 antagonist by a transporter protein that targets axons in the diaphragm of the lung. In a rat model of SCI-induced paralysis of the left diaphragm, intradiaphragmatic injection of the conjugate increased function of the left diaphragm and nerve signaling in the diaphragm compared with injection of gold nanoparticles linked only to the transporter protein. Also in the model, the therapeutically effective dose of the conjugate was 1,000-fold lower than doses previously reported for the free antagonist but did not cause observable CNS side effects. Next steps could include testing efficacy and safety of the nanoparticle conjugate in various models of respiratory complications. ...