Loughborough University scientists use Axol motor neurons to bioengineer a 3D human model of the neuromuscular junction (NMJ), opening the door to translational assays for use in drug development for motor neuron disease.
Following Axol Bioscience and Censo Biotechnologies recent merger to form Axol Biosciences, our CSO Ashley Barnes was
invited to speak at the Neuroimmunology Drug Development Summit
alongside other experts from academia and industry on the advances being
made in this burgeoning field.
In a recent study from the University of Oxford, UK, and TriNetX, US, scientists explored the electronic health records of 236,379 COVID-19 patients and estimated that one-in-three COVID-19 survivors (34%) were diagnosed with a neurological or psychiatric condition within the first six months following infection.
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.
Improving biological tools for disease modelling and drug discovery: human iPSC-derived Atrial Cardiomyocytes
The rapid development of induced pluripotent stem cell-derived cells (iPSCs) is set to revolutionise modern drug discovery through the increased utilisation of human cell reagents in research.
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.
Through the previous blogs in this series, we have understood the challenges which somatic cells face when changing their career path to become induced pluripotent stem cells (iPSCs), the ways in which we can induce this change, and how we might assess whether this is the right career for the cells through pluripotency and differentiation assays.
In our previous blog we likened somatic cell reprogramming to a career change. Once a somatic cell has been converted to an induced pluripotent stem cell (iPSC), the next stage in the process can be thought of as an appraisal or performance review. This is essential to confirming that the reprogrammed cell is behaving as expected.
Cardiovascular diseases (CVD) include coronary heart disease, stroke, myocardial infarction and heart failure. They are the leading cause of mortality globally, with CVD accounting for 31% of deaths worldwide in 2015. Within the UK alone 27.4% of male deaths and 25.2% of female deaths in 2015 were due to CVD.
Traditionally, there have been difficulties in obtaining and culturing human cardiac cells of a high quality due to a scarcity of healthy donor material, culture issues associated with the non-dividing state of terminally differentiated cardiomyocytes. The development of human embryonic stem cell technology allowed major advancements to be made as protocols were developed to differentiate cardiomyocytes from a replenishable pluripotent source. A huge issue with the use of human embryonic stem cell-derived cells was the controversial ethical issues and strict regulations regarding their use. This meant that Yamanaka's breakthrough when his group produced the Nobel Prize winning technology in the form of induced pluripotent stem cells had a gargantuan impact on the study of human cardiac cells.
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.
Somatic cells can be compared to human beings in that they grow up to perform a specific function in life. While a human being may develop into a world class athlete or a research scientist, a somatic cell can develop into any of the cell types that make up an organism except the germline cells.
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.
Download our free white paper ‘Induced Pluripotent Stem Cells: recapitulating disease to facilitate drug discovery‘
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.