All Roads Lead To Oxygen
“One of the most effective ways of saving lives is providing oxygen to patients who need it. Several news reports published today have highlighted the vital role of oxygen in treating patients with severe and critical COVID-19. This has been an area of intense focus for WHO since the beginning of the pandemic.
Patients with severe and critical COVID-19 cannot get enough oxygen into their blood by breathing normally. They need higher concentrations of oxygen and support to get it into their lungs.
Left untreated, severe COVID-19 deprives cells and organs of the oxygen they need, which ultimately leads to organ failure and death.”
Ghebreyesus, Tedros Adhanom. “WHO Director-General’s Opening Remarks at the Media Briefing on COVID-19 – 24 June 2020.” World Health Organization, 24 June 2020Article Link
A Crisis Clarified
There are currently no treatments that are designed to effectively increase oxygen delivery to the vital organs and tissues.
The use of supplemental oxygen via tools like Mechanical Ventilation, Oxygen Mask and Nasal Canular help but do not heal.
What is Hypoxia?
DefinitionHypoxia is the term used to describe a situation where the levels of oxygen are low. There are many diseases or conditions in which hypoxia develops to a part or the entire body.
MultifactorialHypoxia is multifactorial and is prevalent across several diseases including respiratory failure, sepsis, and cardiovascular (CV) disease. For example, tissue hypoxia, particularly those driven by cytokine storms, leads to severe tissue damage. Diseases linked to cytokine storms include COVID-19 and Sepsis.
COVID-19The leading causes of death in patients with severe COVID-19 are due to hypoxia associated with Acute Respiratory Distress Syndrome (ARDS).
Wider ImplicationsBeyond ARDS and COVID-19, hypoxia is implicated in 6 of the top 10 killers of humankind.
"Deprived of oxygen, human life as we know it would not exist on this planet. Oxygen deprivation is a driver of death in 6 of the top 10 killers of humankind. Most humans facing a life and death situation experience oxygen deprivation that is either limited to a tissue, organ or the whole body. At LEAF4Life we are focused on developing innovative medicines that directly address oxygen deprivation (hypoxia) as a critical driver of death in many life-threatening conditions."
A Carefully Crafted Medicine
OriginsFree transcrocetin is a diterpenoid and natural carotenoid found in spices such as saffron, a constituent of the crocus flower and cape jasmine. Saffron, as a spice, has been consumed in many cultures for thousands of years.
LimitationsTherapeutic use of free transcrocetins has been limited by their poor stability and low solubility which limits the bioavailability of transcrocetin. This is further compounded by a short in vivo half-life which limits the pharmacological effect of oxygenation.
DesignLEAF-4L6715 is a carefully crafted liposomal formulation of transcrocetin achieved by entrapping a less soluble, divalent salt of transcrocetin inside the liposome. This construct facilitates the controlled release of transcrocetin from the liposome into blood circulation.
ImpactBy releasing transcrocetin into circulation in a controlled manner, LEAF-4L6715 produces a more sustained oxygenation effect.
Mechanism of Action
Transcrocetin belongs to the class of molecules known as kosmotropes. The hallmark of kosmotropes is to alter the structure of water molecules in aqueous solutions such as water or blood. This altering creates channels through which smaller molecules such as oxygen can more easily travel to reach tissues where oxygen is needed.
In the presence of tissue oxygen deprivation (hypoxia), transcrocetin enhances oxygen diffusion, thereby improving oxygen delivery to affected tissues and organs.
Transcrocetin has been nicknamed “The Moses Molecule” because of its kosmotropic ability to part water.
We Are Responding
We have all been confronted with the necessity to unite and stand together in the fight against COVID-19. Here at LEAF4Life, we are responding effectively to this call to action.
LEAF-4L6715 is currently being studied in a Phase I/II clinical trial of patients with COVID-19.