Efforts at Abbvie Inc. to selectively target voltage-gated sodium channel subunit alpha Nav1.7 to treat pain led to the discovery of quinoline and quinolone agents and, through structure-activity relationship studies, the candidate product ABBV-318. While Nav1.7 potency could be achieved with earlier compounds, efforts were required to improve characteristics including hERG activity, pharmacokinetics and selectivity over Nav1.5, yielding compounds which blocked Nav1.7 as well as another target for treating pain, Nav1.8.
As patients with Pompe disease age, they develop neurocognitive issues and impairment in their cerebral white matter, as shown in MRI scanning. To date, there are no biomarkers that reflect this disease progression in the brain. The usefulness of neurofilament light chain (NfL) was investigated for this purpose.
Glutaric acidemia type I (GA1) is caused by severe deficiency in enzyme glutaryl-CoA dehydrogenase activity, which results in an impairment on lysine catabolism. These patients have accumulation of glutaric acid and glutaryl carnitine, with loss of striatal neurons and atrophy of the frontotemporal cortex. The aim of investigators was to investigate plasma markers of neurodegeneration and inflammation, such as brain-derived neurotrophic factor (BDNF) and cathepsin D in patients (N = 6) with GA1 and matched healthy controls.
A recent paper in the Journal of Neuroscience detailing preclinical research from the University of Texas shone new light on triggering receptor expressed on myeloid cells 2 (Trem2), an increasingly popular target in drug discovery that a handful of companies are pursuing.
Researchers from Istituto di Ricerche Farmacologiche Mario Negri aimed to characterize lectin pathway (LP) activation after ischemic stroke in a novel humanized mouse model expressing human mannose-binding lectin.
Treatment with injections of gonadotropin-releasing hormone (GnRH), indicated to prevent sexual maturation deficits in Down syndrome, also reduced cognitive function impairment associated with Down syndrome, also called trisomy 21. With age, about three-quarters of people with Down syndrome develop Alzheimer's disease. They also lose their sense of smell. Both circumstances could improve with pulse doses of GnRH, according to a study led by the French National Institute of Health and Medical Research (Inserm) and the University of Lausanne (UNIL) published in the Sept. 1, 2022, issue of Science.
International research project Multicentre Epilepsy Lesion Detection (MELD), led by University College London, has developed artificial intelligence software that can identify minute brain anomalies that lead to epilepsy seizures. These anomalies, known as focal cortical dysplasia, can often be treated with surgery but are difficult to visualize on an MRI.
Treatment with injections of gonadotropin-releasing hormone, indicated to prevent sexual maturation deficits in Down syndrome, also reduced cognitive function impairment associated Down syndrome, also called trisomy 21.
Researchers from Pfizer Inc. presented preclinical data for the melanocortin MC4 receptor (MC4R) antagonist PF-07258669, being developed for the treatment of anorexia nervosa.
Circadian rhythm disorders are associated with psychiatric disorders including depression, bipolar disease and schizophrenia. To target casein kinase I isoform delta (CKI-delta), Janssen Pharmaceutica NV scientists sought potent, selective, brain-penetrant CKI-delta inhibitors which can be dosed daily and orally.
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