Due to the large degree of homology among dopamine D2-like receptors, discovering ligands capable of discriminating between the D2, D3, and D4 receptor subtypes remains a significant challenge. The development of subtype-selective pharmaceutical small molecules to activate (agonists) signals regulated by D2-like receptors has been especially difficult.
Some existing therapies for treatment of pain are administered systematically and have significant side effects, such as addiction and drowsiness. Alternative therapy that does not impair normal touch function could be used to treat pain caused by mechanical injury or chronic inflammation. Administration of margaric acid was shown to ameliorate pain in mouse models of pain. In vitro data shows that margaric acid counteracts PIEZO2 (Piezo-type mechanosensitive ion channel component 2) potentiation evoked by bradykinin (i.e.
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and makes up 3% of all childhood cancers. Aveloar Rhabdomyosarcoma is the most aggressive subtype and is primarily established through a chromosomal translocation resulting in the fusion protein PAX3-FOXO1. Despite aggressive therapy, the 5-year survival rate for patients with high risk or recurrent Fusion Positive RMS (FP-RMS) is low (~30% and ~17%, respectively). Therefore, new therapies targeting the PAX3-FOXO1 oncogenic driver are urgently needed.
Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Scientists at the National Cancer Institute (NCI) have developed and characterized an orthotopic genetically engineered mouse (GEM)-derived model of GBM that closely recapitulates various human GBM subtypes and is useful for preclinical evaluation of candidate therapeutics.
There are no analgesics to ameliorate chronic pain without adverse side-effects (e.g., respiratory depression, gastrointestinal effects, tolerance, dependence), thus forcing patients into a difficult choice of negative impacts on quality of life. Most of the analgesics used for chronic and acute pain are drugs such as oxycodone, morphine, oxymorphone, and codeine. All of these opioids have been subject to misuse; prescription drug abuse is a severe problem worldwide, causing high mortality and greatly increased emergency room visits.
Traumatic brain injury (TBI) is a major health problem. Between 3.2 and 5.3 million people live with long-term disabilities resulting from TBI, and thus, contribute to the need to develop therapies that treat TBI-induced cellular damage. Researchers at the National Institute of Child Health and Human Development (NICHD) have developed a device that simulates the pressure waves resulting from explosions.
Scientists at the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) have developed a method implemented as pulse sequences and software to be used with magnetic resonance imaging (MRI) scanners and systems. This technology is available for licensing and commercial development. The method allows for measuring and mapping features of the bulk or average apparent diffusion coefficient (ADC) of water in tissue – aiding in stroke diagnosis and cancer therapy assessment.
The limited choice in cell types available for in vitro studies has become an obstacle in hibernation research.
Researchers at the National Eye Institute for the first time have successfully established iPSC line(s) from a mammalian hibernator, which can be potentially used to generate various cell types and tissue models for in-depth mechanistic studies of hibernation and coldness tolerance in vitro.
Drug delivery technologies have long claimed the ability to selectively deliver therapeutic cargo to target cells. Despite advances in nanomedicine and drug delivery systems, there are no targeted nanoscale drug delivery technologies on the market. Thus, there is still tremendous potential in improved therapeutic efficacy when targeted drug delivery is achieved.
Substance use disorder is a chronic medical condition, taking its toll on our public health care and judicial systems in an economically unsustainable way. More than 20 million Americans suffer from substance use disorders.