Publications by authors named "Laura M Hales"
Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP).
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- Ghrelin has potential therapeutic benefits for cachexia (wasting syndrome) due to its ability to stimulate appetite and promote muscle and fat growth; however, its short active duration limits its use in clinical settings.
- EXT418 is a new long-acting version of ghrelin created by linking it to a vitamin D component, and this study tested its effects on mice suffering from cancer-induced cachexia.
- Results showed that EXT418 significantly reduced weight loss and improved grip strength in mice with tumors, and positively affected muscle fiber sizes, highlighting its potential as a treatment for cachexia.
Peptides have great potential to be potent and specific therapeutics, yet their small size leads to rapid glomerular filtration, which severely limits therapeutic applications. Although conjugation of small proteins to large polymers typically results in longer residence times, these conjugates often have a significant loss of biological activity due to steric hindrance. Here, we improve the pharmacokinetics (PK) of peptide therapeutics by harnessing the biology of vitamin D.
View Article and Find Full Text PDFThe complete genome sequence of Seneca Valley virus-001 (SVV-001), a small RNA virus, was determined and was shown to have typical picornavirus features. The 7280 nt long genome was predicted to contain a 5' untranslated region (UTR) of 666 nt, followed by a single long open reading frame consisting of 6543 nt, which encodes a 2181 aa polyprotein. This polyprotein could potentially be cleaved into 12 polypeptides in the standard picornavirus L-4-3-4 layout.
View Article and Find Full Text PDFBackground: Numerous clinical trials have demonstrated that oncolytic viruses can elicit antitumor responses when they are administered directly into localized cancers. However, the treatment of metastatic disease with oncolytic viruses has been challenging due to the inactivation of viruses by components of human blood and/or to inadequate tumor selectivity.
Methods: We determined the cytolytic potential and selectivity of Seneca Valley Virus-001 (SVV-001), a newly discovered native picornavirus, in neuroendocrine and pediatric tumor cell lines and normal cells.