Microneurotrophins act as 'high-affinity', centrally active agonists of the TrkA, TrkB and p75NTR receptors of Neurotrophins Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Bionature and collaborators have developed new selective agonists for TrkA and TrkB receptors, NGF or BDNF mimetics, tested in animals models of Diabetic retinopathy, Alzheimer’s disease, Parkinson’s disease and demyelinating diseases.
Apoptotic neuronal loss is the common pathophysiological end-point of all neurodegenerative diseases and a large number of experimental and clinical studies implicate neurotrophins in this process. It is now well documented that neurotrophin production declines in the degenerating brain, apparently leaving neuronal cells unprotected against pro-apoptotic insults and decreased capacity of brain regeneration.
Although there are currently scarce effective therapeutic treatments for neurodegenerative diseases, apoptotic loss of neurons remains one of the major therapeutic targets. The effectiveness of neurotrophins in controlling neuronal apoptosis in various experimental animal models of neurodegenerative conditions has not yet been translated to clinical use, which has been hampered by their inability to pass the blood-brain-barrier (BBB) and their unstable serum pharmacokinetics and bioavailability.
Microneurotrophins have been shown to be very effective in preventing and reversing the demyelination and neuronal degeneration
Bionature focuses on the development of novel, proprietary, blood-brain barrier permeable small molecules for the treatment of neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis, diabetic retinopathy, Parkinson and Alzheimer diseases. Bionature's team has discovered that its synthetic small molecules interact with the receptors of the endogenous neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and are therefore referred to as "microneurotrophins". (Calogeropoulou et al J Med Chem 2009, Lazaridis et al PLoS Biol 2011, Pediaditakis et al Neuropharmacology 2016, Front Pharmacol 2016).
Microneurotrophins have been shown to be very effective in preventing and reversing the demyelination and neuronal degeneration observed in the cuprizone model of demyelination and multiple sclerosis (MS) and in preventing apoptosis in models of diabetic retinal degeneration, Alzheimer and Parkinson diseases. They are also strong inducers of neurogenesis in vivo, propagating the formation of fresh neural tissue.
Our research focuses on science related to the neurobiology and neurophysiology of neurodegenerative processes. We implement state of the art technologies, such as reverse genomics, advanced imaging, human disease specific transgenic animals, neural stem cell biology.Our research process Publications
Diabetic retinopathy (DR) is a serious complication of diabetes that leads to loss of visual acuity and blindness. It has been estimated that by 2030 the number of people with DR globally will rise to 191 million from 127 million in 2010. The imbalance between prosurvival neurotrophic factors and inﬂammatory components is believed to lead to apoptosis and proinﬂammatory responses of diabetic retina. Bionature has developed microneurotrophin BNN27, a synthetic small molecule with neuroprotective and anti-neuroinflammatory properties, very effective in animal models of DR, when administered systematically or as eye drops (Iban-Arias et al Diabetes 2018, Iban-Arias et al Graefe's Arch Clin Exp Ophthalmol 2019).
Neurotrophic factors are among the most promising treatments aiming at slowing or stopping and even reversing Parkinson's disease (PD). However, in most cases, they cannot readily cross the human blood-brain-barrier (BBB). Bionature proposes as a therapeutic for PD its proprietary microneurotrophin BNN20, a synthetic molecule which crosses the blood-brain barrier and activates neurotrophin receptor TrkB. Microneurotrophin BNN20 exhibits neuroprotective and anti-neuroinflammatory properties in animals model of Parkinson disease (Botsakis et al, Neuropharmacology 2017, Panagiotakopoulou et al Neuropharmacology 2020).
Although tremendous progress has made in understanding the basic biology of Alzheimer's disease (AD), its etiology is unknown and most therapeutic effects failed. Recent experimental and clinical findings show that one of the potential etiologies is the loss of regenerating capacity in the brain of AD patients in contract to normal brain even at its aged stage. Bionature’s scientists developed blood brain barrier permeable small molecules with strong neuroregenerative properties, both in vitro and in vivo in animal models of AD. Microneurotrophins BNN27 and BNN237 boost neural stem cell proliferation, decrease neurotoxic beta-amyloid levels in the brain of AD 5xFAD transgenic mice and reverses their memory loss as well as in cell and organ-type 3D cultures of human neural stem cells.