Partnerships keep us at the forefront of new drug development

By working closely with leading academic institutions, CROs, and consultants we are producing the evidence needed to establish Proof of Concept in man. The results of our preclinical studies can then be used to take our products in to clinical trials and potentially develop treatments for conditions where no alternatives exist.

“The data we have generated on ILB whilst working with TikoMed are truly unique and throughout my career I can truly say that they are exceptional.”

Professor Ann Logan, Scientific Director, Neuregenix Ltd.

Discovering the science that makes a difference

Our development partnerships have revealed that ILB has the potential to treat glaucoma and several neurological diseases through multiple mechanisms.

ALS

Background
ALS is a progressive neurodegenerative condition often referred to as motor neurone disease. It affects the motor neurons in the brain and spinal cord leading to weakness and wasting of muscles, loss of ambulation, difficulties with speech and swallowing, cognitive dysfunction, and breathlessness. There is currently no cure for ALS and management is focused on a combination of neuroprotective medication, multidisciplinary clinics, and respiratory support.

Disease modifying therapy is limited to Riluzole, which is the ONLY drug that has been approved/licensed for treating ALS. Researchers now aim to slow ALS progression by targeting known pathophysiological pathways.

Studies
In vitro studies performed by our development partner, Neuregenix, have shown ILB could have multiple beneficial effects on factors implicated in the pathogenesis of ALS. These include promoting cell survival, differentiation of glia and neurons, cellular homeostasis, glutamate uptake, angiogenesis, and MBP expression. It is understood to achieve this by multiple mechanisms such as reducing or preventing:

  • Oxidative stress
  • Mitochondrial dysfunction
  • Glutamate excitotoxicity through glial cell activation.

In vivo studies have also shown that ILB enhances the protective effect of growth factors essential in neuronal growth, maintenance, and repair by inducing peripheral production of HGF

Stroke

Ischemic stroke is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. Studies perfomed by our development partner Pharmaseed showed that ILB treatment clearly improved motor and somatosensory deficits as well as cerebral blood perfusion and angiogenic activity.

Regular doses of ILB:

  • Induced resumed blood flow and increased blood vessel size.
  • Accelerated recovery from neurological deficit.
  • Improved motor and somatosensory responses.

“The pleiotropic mechanisms of action of ILB that we have revealed indicate the utility of this drug to treat many acute and chronic degenerative conditions.”

Professor Ann Logan,
Scientific Director, Neuregenix Ltd.

Traumatic brain injury

Tissue damage following traumatic brain injury (TBI) usually leads to the accumulation of lactic acid due to anaerobic glycolysis and the depletion of ATP stores following the failure of energy-dependent membrane ion pumps.Terminal membrane depolarization subsequently occurs along with excessive release of excitatory neurotransmitters such as glutamate and aspartate, which contribute to the pathogenesis of acute neuronal death.

The effects of ILB on antioxidant markers, glutamate excitotoxicity, and mitochondrial function following severe TBI were studied by our development partners Neuregenix.

Antioxidant markers
Compared with controls that suffered traumatic brain injury, ILB treatment:

  • Reduces oxidative stress.
  • Reduces levels of MDA indicating improved recovery of antioxidant status (MDA is an end-product of ROS-mediated lipid peroxidation).
  • Decreases the nitrate concentration.

Glutamate levels
In the acute phase of TBI, ILB treatment decreased glutamate-induced excitotoxicity.

Mitochondrial function
Changed levels of adenine nucleotides and the ATP/ADP ratio provide a measurement of mitochondrial phosphorylating capacity. Treatment with ILB showed it interfered with mitochondrial function to improve energy metabolism. Remarkable changes of oxidative and reduced nicotinic coenzymes were also observed.

The results of these studies suggest ILB interferes with mitochondrial function to improve energy metabolism and decreases glutamate excitotoxicity following TBI.

Glaucoma

Background
Chronically raised intraocular pressure (IOP) is a major risk factor for the development of Primary Open Angle Glaucoma (POAG). Reduced outflow of aqueous humour secondary to fibrosis in the Trabecular Meshwork (TM) elevates IOP causing Retinal Ganglion Cell (RGC) death and blindness. Currently, reduction of IOP is recognised as the only modifiable risk factor for POAG achieved by surgery and chemotherapeutic treatments.

Study
Our development partner, Neuregenix, investigated the effects of ILB on reducing TM fibrosis, lowering IOP, and protecting RGC from death. They demonstrated ILB suppresses scar formation and reverses established scarring by modulating fibrogenic growth factor activity and activating proteases that lyse collagen, fibronectin, and laminin.

Conclusions
ILB treatment led to:

  • A fall in IOP that probably resulted from dissolution of established TM scar elements.
  • Restoration of normal IOP levels associated with preservation of RGC.
  • A reversal of the glaucomatous pathology that leads to progressive vision loss.

Neuregenix concluded that ILB is an alternative treatment strategy for established POAG and has the potential to prevent progressive visual loss by lowering IOP through dissolution of TM fibrosis thereby protecting RGC from progressive apoptosis.

Neurodegeneration

in vitro gene expression studies performed by our research partner, Neuregenix, have revealed multiple effects of ILB on triggers that cause neurodegeneration. By identifying how ILB targets multiple pathological processes and contributes to the protection and repair of neurons, we can better understand its potential as a future treatment for neurodegenerative disease.

  • Addresses neurotransmitter dysregulation.
  • Improves the neuronal energy supply by protecting mitochondria from oxidative stress.
  • Prevents axonal neurofilament accumulation and axonal transport dysfunction including hyper-excitability.
  • Prevents release of inflammatory mediators, secondary cell damage, and tissue scarring.
  • Improves vascular oxygen and nutrient supply by facilitating the activity of angiogenic growth factors.