The need:
Worldwide, Traumatic Brain Injury (TBI) is a major cause of
mortality and morbidity with a substantial predicted increase
in incidences.
Preclinical studies and conversion of new neuron-protection
molecules to clinical practice has failed so far.
Despite an obvious need, there are currently no
pharmacological treatment options for TBI.
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
TBI is a major cause of morbidity and mortality worldwide, with an
incidence of 235 per 100,000 people and a worldwide mortality of
more then 1.5 million per year.
The public health impact of TBI is expected to increase because the
most common cause of TBI is road traffic accidents. It is projected
to become the fourth leading cause of disability by 2030.
In addition, TBI is a major problem in combat areas/war zone -The
New England Journal of Medicine reported a study where over 15%
of soldiers in Iraq are suffering from Traumatic Brian Injuries.
“Pentagon estimates up to 360,000 cases of brain injury suffered by
veterans of the wars in Iraq and Afghanistan (2009)”.
TBI market:
Currently, no effective TBI therapy exists, with patients treated through a
combination of surgery, rehabilitation and pharmacological agents managing posttrauma conditions such as depression. Consequently, the estimations for global
market value for TBI therapy is in the region of US$10 billion, with the majority
of this accounted for by the demand across Europe and in the United States.
Forecast Value of the Traumatic Brain Injury Market in the United States 2015-2020
(Assuming first products launched within the next three years. Source: Arrowhead Publishers)
TBI: Complex problem- creative solution
 TBI is a highly complex disorder that includes varying degrees
of contusion, diffuse axonal injury, hemorrhage and hypoxia.
Collectively, these effects induce biochemical and metabolic changes
that lead to progressive tissue damage and associated cell death.
 Both the early primary events and the delayed secondary alterations
contribute to the resulting neurological deficits.
 Although preclinical studies have suggested many promising
pharmacological agents, more than 30 phase III prospective clinical
trials have failed to show significance for their primary endpoint.
 Most of these trials targeted single factors proposed to mediate
secondary injury.
 But the complexity and diversity of secondary injury mechanisms have
led to calls to target multiple delayed injury factors, either by
combining agents that have complementary effects or by using
multipotential drugs that modulate multiple injury mechanisms.
Innovation:
Innovative molecules that have a unique combination of
properties were designed.
In the clinic, we will not introduce one molecule with one
effect but rather a combination of activities tackling
several cascades using a specific compound with more
then one activity.
Chemistry:
We have designed a bank of chemically verified molecules that can
cross the blood-brain barrier (BBB), each possessing an inovative
chemical spacer with two or more of the following properties for
preventing secondary brain deterioration in TBI patients:
• Binding of free metal ions
• Anti-oxidation,
• Anti-inflammation
• Anti-bacterial.
Work plan:
1)
Chemistry, optimization of synthesis, improving yields, setting up an
analytical method (HPLC), accumulating data on solubility, stability in solution and
in plasma. Membrane permeability, Kd’s and LogD will be calculated. Formulations
to optimize the method of treatment will be developed.
2)
In-Vitro, Preliminary information of toxicity to cells will be tested
(XTT, LDH). A new and innovative method for neuronal growth and monitoring
single cell response to stimuli was set-up and now efficiency will be
demonstrated. The LCA (liveCell array, Nunc) modified for neurons and glial cells
will be recruited to demonstrate neuroprotection.
3)
In-Vivo, compounds in the appropriate formulation will be tested in TBI
models. A rat model of percussion injury is calibrated, tested and ready to be
used in order to demonstrate efficacy. We have set-up several behavioral,
memory and function tests to evaluate the outcome of the treatment. In
addition we have an ElISA test optimized to measure and follow-up a marker,
specific to prediction of the outcome of TBI in rats.
The LCA (liveCell array™) innovative system
The LCA system is used for in-vitro Proof Of Concept (POC)
Other Brain Injuries:
Open head Injury -Results from bullet/shred wounds.
Closed Head Injury -Resulting from a slip, fall and motor vehicle crashes.
Deceleration Injuries -The differential movement of the skull and the brain
when the head is struck, results in diffuse axonal shearing of the brain that
is slammed back and forth inside the skull. It is alternately compressed and
stretched because of the gelatinous consistency.
Chemical & Toxic -Also known as metabolic disorders. This occurs when
harmful chemicals include insecticides, solvents, carbon monoxide poisoning,
lead poisoning, etc. damage the neurons.
Hypoxia (Lack of Oxygen) - When the blood flow is depleted of oxygen, even
for a few minutes, then irreversible brain injury can occur from anoxia (no
oxygen) or hypoxia (reduced oxygen). This condition may be caused by heart
attacks, respiratory failure, drops in blood pressure and a low oxygen
environment.
Tumors -Tumors can cause brain injury by invading the spaces of the brain
leading to direct damage. Damage can also result from pressure effects
around an enlarged tumor. Surgical procedures aimed at removing the tumor
may also contribute to brain injury
Infections -Viruses and bacteria can cause serious and life-threatening
diseases of the brain (encephalitis) and meninges (meningitis)
Stroke -If blood flow is blocked through a cerebral vascular accident, cell
death will result in the area deprived of blood. If there is bleeding in or over
the brain (hemorrhage or hematoma) due to a tear in an artery or vein, loss
of blood flow and injury to the brain tissue by the blood will also result in
brain damage
General awareness:
General Colin L. Powell, USA (Ret.)
USA grants:
MediCortex USA
•Medicortex is registered as an American company.
•At the present, the company is being run on personal capital.
•Currently, we are looking for the seed investment of $200,000 US
•The next milestone will be reached after proof of concept and a
demonstration of efficacy. Therefore making the company worth an
estimated $2-$3 M
•The use of proceeds raised is not for salary, it will be for:
•1) chemical synthesis
•2) in-vitro toxicology
•3) in-vivo efficacy
Contact:
Dr. Adrian Harel
Tel:+972-54-4727696
E-mail: hareladrian@yahoo.com
www.medicortex.com