Science behind NBTX-001

NBTX-001’s active ingredient is the noble gas xenon. This gas was discovered to have unique biological properties1, has a remarkable safety profile2, has been extensively used in imaging3 and is approved in some jurisdictions for use in general anesthesia4. It is a non-psychomimetic, non-habit forming, non-flammable, non-greenhouse gas with rapid bioavailability and rapid brain penetrance5.

Interaction of xenon atoms with aromatic amino-acid residues on NMDA receptors provides highly specific and controllable antagonism6. In addition, it reduces excitatory neurotransmission by blocking AMPA, nACh (α4β2), 5-HT3, plasma membrane Ca2+ ATPase and increases inhibitory neurotransmission by stimulating GlyR1 and TREK-1 potassium channel. It is also shown to reduce pro-inflammatory cytokines (tumor necrosis factor α, interleukin 1β), to increase pro-survival factors (bcl2), and growth factor production (BDNF, IGF).

Dr. Edward Meloni from Harvard University demonstrated that rodents exposed to xenon (25%, 1 h) immediately after fear memory reactivation exhibited a significant reduction of freezing – a measure of fear in animals – when tested 48 and 96 h after reactivation compared to air-exposed controls7.

Dr. Daqing Ma from Imperial College of London demonstrated xenon’s organoprotective properties in animals after organ transplantation8. Most recently, and based on Dr. Ma’s preclinical work a human study has shown a reduction in white matter damage when xenon is given after cardiac arrest9. Preliminary data from Dr. Ma’s laboratory has shown very promising results of xenon administration in Alzheimer’s disease model (confidential data on file, patent filed by Nobilis Therapeutics).

Russia is a pioneer in the medical application of noble gases and Dr. Dobrovolsky is one of the most notable clinical experts in the field of xenon use in patients with psychiatric conditions. He has completed an 80-patient open-label study of xenon use in panic attacks and demonstrated excellent efficacy and tolerability. Additionally, he has performed a 50 patient open-label study of xenon treatment in alcohol and drug addiction in which he demonstrated excellent efficacy and tolerability both as a monotherapy and in combination with psychotropes (confidential data on file and articles in print).

Cullen SC, Gross EG. The anesthetic properties of xenon in animals and human beings, with additional observations on krypton. Science. May 18 1951;113(2942):580-582.
2 Latchaw, R.E., et al., Adverse reactions to xenon-enhanced CT cerebral blood flow determination. Radiology, 1987. 163(1): p. 251-4.
3 Carlson, A.P., et al., Xenon-enhanced cerebral blood flow at 28% xenon provides uniquely safe access to quantitative, clinically useful cerebral blood flow information: a multicenter study. Am J Neuroradiol. 32(7): p. 1315-20.
4 Dickinson R, Franks NP. Bench-to-bedside review: Molecular pharmacology and clinical use of inert gases in anesthesia and neuroprotection. Crit Care.14(4):229
5 Dickinson R, et al. Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. Anesthesiology. Nov 2007;107(5):756-767
6 Andrijchenko  et al. Toward molecular mechanism of xenon anesthesia: a link to studies of xenon complexes with small aromatic molecules. J Phys Chem A. 2015 Mar 19;119(11):2517-21
7 Meloni EG, et al. Xenon impairs reconsolidation of fear memories in a rat model of post-traumatic stress disorder (PTSD). PLoS One. 2014 Aug 27;9(8):e106189
8 Ma D, et. al. Xenon Treatment Protects against Remote Lung Injury after Kidney Transplantation in Rats. Anesthesiology. 2015 Jun;122(6):1312-26
9 Laitio R. et. al. Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2016 Mar 15;315(11):1120-8