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All pharmaceutical development programs carry a certain amount of risk. However, when it comes to developing drugs that target the central nervous system, the odds of success narrow significantly.
Amyotrophic Lateral Sclerosis (ALS), a Motor Neuron Disease (MND) subtype, is a debilitating neurodegenerative disorder affecting the upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord. This leads to progressive muscular weakness and atrophy, paralysis, and eventually death, usually within three to five years after the onset of symptoms. Decades of failed drug development mean that MND/ALS is still incurable; only two FDA-approved drugs exist (riluzole, and more recently, edaravone), but these only slow down disease progression.
Human iPSC-Derived Motor Neurons: Expert tips on best cell-culture practices to enhance your research
Despite intensive research, there is still no known cure or standard treatment for Amyotrophic Lateral Sclerosis (ALS), a Motor Neuron Disease (MND) subtype. Researchers have traditionally used animal models (usually mice) to screen candidate compounds, but these models are now known to lack physiological relevance to the human pathology, which could limit translational drug development.
Kidneys play a key role in removing waste and toxins from the body, as well as having essential endocrinological and homeostatic functions. If certain pharmaceuticals are abused, administered incorrectly or taken regularly, they can induce toxicity in the kidneys (nephrotoxicity). This can result in impaired renal function, and even death in the most severe cases. For example, nephrotoxic drugs (NDs) are responsible for 19-25% of acute kidney injury in critically ill patients.
Enhancing Amyotrophic Lateral Sclerosis (ALS) drug discovery using physiologically relevant hiPSC-Derived Motor Neurons
Amyotrophic Lateral Sclerosis (ALS), a Motor Neurone Disease (MND) subtype is characterised by the degeneration and death of nerves (motor neurons) in the brain and the spinal cord that control essential voluntary muscle activity. Affecting over 400,000 patients worldwide each year, MND/ALS progressively causes difficulties in speaking, walking, breathing, and swallowing, with the disease eventually being fatal in about a quarter of all patients affected each year.
Guest Post: Are 3D neural cell cultures the best translational models towards finding a cure for Alzheimer's disease?
Diagnosed by the German psychiatrist and neuropathologist, Dr. Alois Alzheimer in 1906, Alzheimer’s disease (AD) is the most prevalent form of dementia in the ageing population (Korolev et al., 2014). Recently declared as the sixth major cause of death in the world; patients affected with AD suffer a gradual decline of cognitive abilities and memory functions till the disease renders them incapable of performing daily activities. Some of these traits, which are typical of neurodegenerative diseases are also shared by other forms of dementia.
The brain is the most complex organ in the body, controlling our highest functions, as well as regulating myriad processes which incorporate the entire physiological system. There is a significant risk that a novel therapeutic agent might impact brain structure and function, resulting in serious pathologies and even death. Therefore, CNS testing forms part of the 'core battery' of safety pharmacology studies .
There are different non-integrating reprogramming systems available to researchers along with the approaches Axol uses to generate hiPSCs from your cells. This white paper can help you choose the best cell reprogramming approach for your research needs.
The body’s immune system is our first line of defence against foreign substances, protecting us against infection and disease. It consists of a complex network of organs and cells that work to recognize and destroy these harmful substances, containing them at the site of infection. Macrophages play a crucial role in this; engulfing and destroying anything dangerous via phagocytosis.
The human immune response consists of a complex network of cells working together to identify and destroy foreign substances in the body. Two key players in this response mechanism are: 1) circulating peripheral blood monocytes, the cells first to the site of interest; and 2) macrophages, which arise at the point of injury or infection through differentiation of these monocytes into tissue-specific macrophages. Macrophages are responsible for destroying the foreign body before further infection occurs.
Millions of people around the world suffer from debilitating pain. However, with impressive advances being made in pain research and drug discovery efforts, researchers are continuing to delve deeper into the molecular pathways underpinning pain, to ultimately improve both the screening of drug candidates and the quality of life for people across the world.
Innovations in biotechnology and advances in stem cell biology are currently revolutionizing biomedical research and drug discovery. One exciting breakthrough has been the ability to produce sensory neurons from human induced pluripotent stem cells (hiPSCs) and culture them in vitro on multi-electrode array (MEA) systems, to advance pain research and the discovery of effective pain therapies.
Axol Bioscience Travel Grant recipient, Helen Rowland, attended the ISSCR 2017, which took place in Boston, USA. Helen is a neuroscientist at the University of Manchester, UK. She shares her experience of the conference where she presented her research.
Axol Travel Grant Recipient: European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society 2017
Axol Bioscience Travel Grant recipient, Eseelle Hendow, attended the European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society 2017, which took place in Davos, Switzerland. Eseelle is a cardiovascular researcher at University College London, UK. She shares her experience of the conference where she presented her research.
Millions of people around the world suffer from debilitating pain, causing immense suffering and reducing their quality of life. With the economic costs of chronic pain estimated to be up to $635 billion each year in the US alone , it’s crucial for scientists to be able to fully understand the functionality of human sensory neurons and how they respond to potential new drugs. In the race to find effective treatments, scientists commonly study in vitro neuron cultures to characterize the molecular pathways underlying pain, which can help to identify therapeutic targets and quickly screen potential drug candidates.
Age, diabetes and having the two copies of the gene for apolipoprotein E 4 (APOE ε4) are just some of the factors that significantly increase the chance of developing Alzheimer’s disease later on in life. Associate Professor Carmela Matrone’s research group used stem cells generated from Alzheimer’s disease patients with the APOE ε4 gene to show that this genetic risk factor is connected to a deterioration of a relationship between two key proteins, sortilin-related receptor (SORL1) and amyloid precursor protein (APP) 1 .
Axol Bioscience Science Scholarship recipient, Nataly Martynyuk, is a PhD student at the Brain Repair Centre, Department of Clinical Neurosciences, University of Cambridge, UK. Her research focuses on the actions of alpha-chimerins in mechanisms relevant to dendritic spine formation and neurodegeneration. Nataly reviews the development and degeneration of dopaminergic neurons and discusses the role of dopamine and alpha-synuclein in Parkinson's disease.
Axol Bioscience Science Scholarship recipient, Nataly Martynyuk, is a PhD student at the Brain Repair Centre, Department of Clinical Neurosciences, University of Cambridge, UK. Her research focuses on the actions of alpha-chimerins in mechanisms relevant to dendritic spine formation and neurodegeneration. Nataly reviews the evolution of astrocyte research, their biological form and function, and the role they play in human consciousness and memory formation.
Axol Bioscience Travel Grant recipient, Marie Franquin, attended the Gordon Research Conference - Neurobiology of Brain Disorders 2016, which took place in Girona, Spain. Marie is a PhD student at the Centre for Research in Neuroscience, McGill University, Canada. Her research focuses on the role of TNF alpha on synaptic plasticity defects in neurodegenerative diseases using a mouse model and a human model of induced pluripotent stem cell derived (iPSC)-derived neurons and iPSC-derived astrocytes. Marie shares her experience of the conference where she presented her research.