Pharmaceuticals & Vitamin D : Immunity & auto-immune

UW–Madison researchers led by Prof. Hector DeLuca have discovered that two specific salate esters commonly found in sunscreen almost completely prevented experimental autoimmune encephalomyelitis (EAE) development in mice without affecting body weight. Salicylates are well-known nonsteroidal anti-inflammatory drugs (NSAIDs); the complete suppression of EAE by topical administration of homosalate and octyl salicylate is a novel finding.

UW–Madison researchers have developed a vitamin D analog, seco-A-2,19-dinor-1,25-dihydroxyvitamin D₃. Known as DA2HE, the compound exhibits high activity in vivo, especially in intestinal tissues. Relatively low receptor binding, differentiation and transcription activities suggest strong cell selectivity for use against polyps, some cancers and intestinal disorders. The compound’s high intestinal calcium transport activity may be useful against bone diseases.

UW–Madison researchers have developed vitamin D analogs (20S) and (20R)- 1a,25-dihydroxy-2-methylene-vitamin D₃ and (5E)-(20S)-1a,25-dihysroxy-2-methylene-vitamin D₃.These compounds exhibit high binding affinity and cell differentiation activity, suggesting anticancer properties. Also, high calcemic activity may be harnessed for the treatment of bone diseases where less frequent doses are desired.

UW–Madison researchers have developed vitamin D analogs (20S) and (20R)-25-hydroxy-2-methylene-vitamin D₃. In vivo, these compounds could act as prodrugs since 1-hydroxylation can occur in a regulated manner and extended vitamin release activity is predicted. The compounds exhibit high binding affinity and cell differentiation activity, suggesting anticancer properties. Also, high calcemic activity may be harnessed for bone disease treatments in which less frequent doses are preferred, like senile osteoporosis.

UW–Madison researchers have developed vitamin D analogs (20S) and (20R)-3-desoxy-1a,25-dihydroxy-2-methylene vitamin D₃.These compounds are known also as 3D-QMS and 3D-QM, respectively. They exhibit anticancer properties of high binding affinity and cell differentiation activity. High calcemic activity suggests treatment for bone ailments and diseases.

UW–Madison researchers have developed vitamin D analogs,(20S)-3-desoxy-2-methylene-1a,25-diydroxy-19-nor-vitamin D₃ and (20R)-3-desoxy-2-methylene-1a,25-diydroxy-19-nor-vitamin D₃.These compounds exhibit promising anti-cancer activities: high receptor binding, and the arrest and induced-differentiation of proliferating cells. High calcemic mobilization suggests particular effectiveness in the treatment of bone diseases.

A UW–Madison researcher has developed novel TTN analogs, which may be potentially useful for the treatment of cancer or autoimmune disorders. The researcher previously cloned and sequenced the biosynthetic gene cluster for TTN.  He discovered that inactivating two genes, ttnD and ttnF, abolishes production of TTN and leads to the production of five new TTN analogs. 

WARF reference number P100290US03 describes the use of the analogs to inhibit the oncogene SHP-2. In addition to autoimmune disorders, the analogs can be used to treat diseases related to SHP-2, including Noonan syndrome, Leopard syndrome, leukemia and solid tumors.

UW-Madison researchers have developed methods of preventing and treating MS by administering synthetic calcitonin, calcitonin-like peptides or calcitonin mimetics to a patient to diminish MS symptoms.  Vitamin D analogs can be administered in combination with the calcitonin to further reduce symptoms. 

UW-Madison researchers have developed a method of treating an autoimmune complex disease by administering an amount of conjugated linoleic acid (CLA). Administering CLA is believed to be effective because CLA can affect the production of prostaglandins and leukotrienes in humans and animals. This in turn reduces the formation of damaging immune complexes and cellular infiltrates.