Three reasons why iPSC-derived atrial cardiomyocytes are poised to accelerate atrial fibrillation research
Atrial fibrillation is estimated to affect around 6 million people in Europe, making it the most common arrhythmia observed in the clinic. The irregular heartbeat and disturbed electrical activity experienced by atrial fibrillation patients is commonly treated by surgical interventions such as pacemakers or the ablation of diseased tissue, or with non-selective class IC (Nav) and III (Kv) ion channel anti-arrhythmic drugs. However, these approaches can have serious side-effects, so extensive research has been devoted to better understand the cellular mechanisms behind the disease to develop safer and more effective treatments.
Atrial fibrillation is the most common arrhythmia observed in the clinic, affecting 6 million patients in Europe and accounting for 30% of strokes. The prevalence of atrial fibrillation continues to grow due to an aging population and is expected to double over the next 50 years. Given the need to develop safer and more effective anti-arrhythmic therapeutics, considerable efforts have been made to understand the cellular mechanisms of the disease and translate this knowledge into innovative treatments.
Until recently, despite being the most prominent cell type in the human brain, research on astrocytes has been overshadowed by neurons. Once thought to only provide structural support to neurons it has become clear that astrocytes are a vastly heterogenous population of cells with varied functions and roles to match.
Neuropathic pain is a debilitating side effect of many commonly-used chemotherapy drugs, and in severe cases can result in the discontinuation of a cancer treatment. By understanding the mechanisms through which chemotherapeutics induce neuropathic pain, researchers aim to develop effective treatments designed specifically to alleviate the condition. These will combat the dose-limitation imposed on chemotherapeutics, as well as offering utility for conditions including multiple sclerosis, diabetes and HIV.
Understanding the mechanisms of chemotherapy induced neuropathic pain using iPSC-derived sensory neurons
Many commonly used chemotherapy drugs cause unpleasant side effects and complications. Of these, neuropathic pain can be particularly debilitating. Most of the current treatments for neuropathic pain are medications that were originally approved for other health disorders, such as anti-depressants and anti-seizure drugs. These have their own accompanying problems, and since no single drug is effective against all forms of neuropathic pain, it is essential that new therapeutic agents are developed specifically for the treatment of this condition.
Drug toxicity is a significant cause of clinical failure, accounting for approximately one third of all pipeline attrition. This has driven huge interest across the pharmaceutical industry to understand drug toxicity early within the drug development pipeline. The aim of this is to de-risk drug candidates from a safety perspective before they enter the clinic, as well as reducing the substantial costs associated with drug development.
Characterized by their star-like shape astrocytes, also known as astroglia, represent the most abundant cell type in the brain. Closely linked to neurons with pivotal roles in synaptic activity and blood-brain barrier function, the study of astrocytes using in vitro co-culture models is becoming increasingly important in neuroscience research.
Using hiPSC-Derived Renal Proximal Tubular Cells in vitro assays to advance disease research and drug development
The rising numbers of kidney patients and a shortage of transplantable organs is a global health issue with high economic costs. Previous disease research and drug development has traditionally used animal models, but these fail to recapitulate human renal cellular function and so limit our ability to elucidate disease mechanisms and therapeutic targets.
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 .
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.
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.
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 .