Our Ideas

Critical care has many unmet needs, so we have many potential solutions

 

Potential therapeutic benefits of inhaled nitric oxide (iNO): IK-3001     Read more

Pulmonary hypertension is an underlying cause of many critical conditions. When blood vessels in the lungs become constricted, elevated pressures can lead to inadequate oxygenation.1 Some of these conditions include:

  • Hypoxic respiratory failure (HRF): inadequate oxygen supply to the body's organs and tissues2,3
  • Bronchopulmonary dysplasia (BPD): long-term lung damage caused by insufficient oxygenation, inflammation, and structural changes to the lung due to mechanical ventilation4
  • Insufficient cardiopulmonary function: the heart can develop a reduced capacity to circulate the blood. This can be present during certain cardiac and pulmonary surgeries5

 

Inspired by the promise of nitric oxide, our research and development program continues to expand the possibilities.6-9 We are actively searching for new uses for iNO in special patient populations, and are conducting studies that address interesting scientific questions and unmet medical needs for critical care patients.

 

Potential therapeutic benefits of terlipressin: IK-4001     Read more

Hepatorenal syndrome, or HRS Type I, is a rare and often fatal condition of advancing kidney failure in patients with cirrhosis or other severe liver diseases. In many of these patients, a successful liver transplant is their only hope to restore normal kidney function in the long term.

 

Unfortunately, many patients with end-stage liver disease and HRS Type I may not survive long enough to receive a donor organ. Currently there is no FDA-approved pharmacological agent on the market to reverse HRS Type I.

 

Terlipressin helps to increase the likelihood of HRS Type I reversal by redistributing blood flow to the kidneys. By jump-starting normal renal function, terlipressin allows patients to get past the immediate crisis of HRS Type I.10-13

 

Potential therapeutic benefits of IK-5001     READ MORE

IK-5001 is a potential treatment for preventing pathological cardiac remodeling following acute myocardial infarction.†14

 

Currently in a Phase I/II clinical trial, IK-5001 is administered via the coronary artery during standard catheterization and flows into the damaged heart muscle, where it forms a protective “scaffold” that enhances the mechanical strength of the heart muscle during recovery and repair.
Potential therapeutic benefits of hydrogen sulfide (H2S): IK-1001 (delivered intravenously as sodium sulfide)     Read more

Heart cells begin to die in about 20 minutes without oxygen. Brain cells perish in five minutes.15 So for the millions of people who suffer massive heart attacks, strokes or trauma, or who undergo surgery where oxygen is deprived from their bodies, like heart bypass, getting a few minutes of H2S to buy the time they need to receive the critical care could mean all the difference.

 

Thanks to the pioneering research by Dr. Mark Roth focused on suspended animation in cells, tissues, organs, and whole organisms, Ikaria is on the verge of unlocking the secrets of reversible hibernation in humans to help buy more time for oxygen-deprived patients.16 H2S has the potential to modulate metabolism to a state in which cells need less energy and oxygen. This may help lengthen the period of time that tissues and cells can survive without oxygen in various forms of critical illness.17-22

 

H2S, which like NO and CO is a gaseous molecule that is produced by the body's own enzyme system, also has a number of additional therapeutic modes of action, ranging from regulation of gene expression to inhibition of oxidative injury, which contribute to its therapeutic action.23-27 Preclinical studies suggest that sulfide may be useful in the management of multiple conditions that are caused by oxygen deprivation.16,22

 

Potential therapeutic benefits of IK-600X portfolio     READ MORE

Investigational fibrin-derived compounds, known as IK-600X portfolio,* are being studied to preserve endothelial barrier function and prevent tissue injury,† providing an opportunity for exploration in a multitude of conditions impacting the lives of critically ill patients.28,29


These compounds are fibrin-derived peptides that bind to vascular endothelial cells, preserving endothelial barrier function and preventing tissue injury. These novel peptides, which are modified fragments of naturally occurring proteins, are being developed to augment the body’s natural protective mechanisms by preventing vascular leakage, leukocyte transmigration, and capillary vasoconstriction.


Through Phase I and II human trials, as well as through animal disease models, IK-6001 has shown a safety profile and mechanism of action which may offer promise for many critical care conditions that Ikaria is targeting in its research and development efforts.

* IK-600X portfolio – Licensed from Fibrex Medical (FX06, FX201, FX107).
† In animal disease models.

 

References

  1. American Heart Association. Pulmonary hypertension. http://www.americanheart.org/print_presenter.jhtml;jsessionid= F33EDO1SO4S3GCQFCXPSDSQ?identifier=11076. Accessed May 15, 2009.
  2. The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. New Engl J Med. 1997:336:597-604.
  3. Hypoxia [definition]. Dorland's Illustrated Medical Dictionary. 31st ed. Philadelphia, PA: Saunders; 2007:900.
  4. National Heart Lung and Blood Institute Diseases and Conditions Index. What is bronchopulmonary dysplasia? http://www.nhlbi.nih.gov/health/dci/Diseases/Bpd/Bpd_WhatIs.html. Accessed May 15, 2009.
  5. Cardiovascular Research Institute. Pyruvate augmentation of catecholamine-induced cardiac performance. http://www.hsc.unt.edu/research/ifd/cri/documents/PYRUVATE.htm. Accessed May 15, 2009.
  6. Bloch KD, Ichinose F, Roberts JD Jr, Zapol WM. Inhaled NO as a therapeutic agent. Cardiovasc Res. 2007;75(2):339-348.
  7. Clark RH, Kueser TJ, Walker MW, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med. 2000;342:469-474.
  8. Kinsella JP, Abman SH. Inhaled nitric oxide in the premature newborn. J Pediatr. 2007;151(1):10-15.
  9. INOMAX [package insert]. Clinton, NJ: INO Therapeutics LLC; 2007.
  10. Saner FH, Canbay A, Gerken G, Broelsch CE. Pharmacology, clinical efficacy and safety of terlipressin in esophageal varices bleeding, septic shock and hepatorenal syndrome. Expert Rev Gastroenterol Hepatol. 2007;1(2):207-217.
  11. Döhler KD, Meyer M. Vasopressin analogues in the treatment of hepatorenal syndrome and gastrointestinal haemorrhage. Best Pract Res Clin Anaesthesiol. 2008;22(2):335-350.
  12. Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134(5):1360-1368.
  13. Fabrizi F, Dixit V, Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther. 2006;24(6):935-944.
  14. Landa N, Miller L, Feinberg MS, et al. Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat. Circulation. 2008;117(11):1388-1396.
  15. McGowan Institute for Regenerative Medicine. Radical cooling may save trauma victims. http://www.mirm.pitt.edu/news/article.asp?qEmpID=273. Accessed May 15, 2009.
  16. Blackstone E, Morrison M, Roth MB. H2S induces a suspended animation-like state in mice. Science. 2005;308(5721):518.
  17. Kimura H. Hydrogen sulfide as a neuromodulator. Mol Neurobiol. 2002;26(1):13-19.
  18. Fiorucci S, Distrutti E, Cirino G, Wallace JL. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology. 2006;131(1):259-271.
  19. Szabó C. Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov. 2007;6(11):917-935.
  20. Li L, Moore PK. Putative biological roles of hydrogen sulfide in health and disease: a breath of not so fresh air? Trends Pharmacol Sci. 2008;29:84-90.
  21. Mancardi D, Penna C, Merlino A, Del Soldato P, Wink DA, Pagliaro P. Physiological and pharmacological features of the novel gasotransmitter: hydrogen sulfide. Biochim Biophys Acta. 2009. doi:10.1016/j.bbabio.2009.03.05.
  22. Morrison ML, Blackwood JE, Lockett SL, Iwata A, Winn RK, Roth MB. Surviving blood loss using hydrogen sulfide. J Trauma. 2008;65(1):183-188.
  23. Elrod JW, Calvert JW, Morrison J, et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci USA. 2007;104(39):15560-15565.
  24. Sodha NR, Clements RT, Feng J, et al. The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury. Eur J Cardiothorac Surg. 2008;33(5):906-913.
  25. Esechie A, Kiss L, Olah G, et al. Protective effect of hydrogen sulfide in a murine model of acute lung injury induced by combined burn and smoke inhalation. Clin Sci (Lond). 2008;115(3):91-97.
  26. Simon F, Giudici R, Duy CN, et al. Hemodynamic and metabolic effects of hydrogen sulfide during porcine ischemia/reperfusion injury. Shock. 2008;30(4):359-364.
  27. Jha S, Calvert JW, Duranski MR, Ramachandran A, Lefer DJ. Hydrogen sulfide attenuates hepatic ischemia-reperfusion injury: role of antioxidant and antiapoptotic signaling. Am J Physiol Heart Circ Physiol. 2008;295(2):H801-H806.
  28. Gröger M, Pasteiner W, Ignatyev G, et al. Peptide Bß15-42 preserves endothelial barrier function in shock. PLoS One. 2009;4(4):e5391.

  29. Roesner JP, Petzelbauer P, Koch A, et al. Bß15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion. Crit Care Med. 2009;37(2):598-605.