OK Ladies & Gentlemen, we haven’t blogged since mid-March. But no, H.M. Pharma Consultancy has not folded or been taken over. The entire team is fine, and we are going strong – even stronger than before actually, and this means that at some times we must prioritize our limited capacities. Even so, we have been keeping track of interesting drug repurposing patent applications that were published by the WIPO during March and April 2013. Five are briefly discussed here. As always… enjoy!
A Kinase Inhibitor For A Genetic Developmental Disorder
Noonan syndrome (PDF) is a relatively common (0.025 – 0.1%of newborns) genetic multisystem disorder that is characterized by short staturewith mild craniofacial and chest dysmorphy, cardiovascular problems,and delayed sexual maturation.Itis caused by mutations which dysregulate the RAS-MAPK pathway, and have been identified in PTPN11, SOS1, RAF1, KRAS, BRAF, SHOC2and NRAS(Lancet2013; 381(9863):333-342, here; Postepy Biochem. 2012; 58(3):255-264, here).The mitogen-activated protein kinase/extracellullar signal-regulated kinase kinase (MEK) being a key element in this pathway (activated MEK phosphorylates the MAP kinases, ERK1 and 2), it was suggestive to claim theMEK inhibitor, MEK162 (first investigated by Array Biopharmaceuticals as ARRY-162[PDF] and now developed by Novartisunder a 2010 agreement)in WO/2013/033133(Novartis AG [CH]; March 7, 2013). MEK162 is in several clinical trials for various solid tumors, and NCT01556568, a Phase II trial for hypertrophic cardiomyopathy in Noonan syndrome, iscurrently recruiting participants and estimated to be completed in October 2013. Also see WO/2012/019113claiming ERK inhibitors for developmental disorders of neural connectivity.
Diclofenac For Influenza And Common Cold
So what, you might say — NSAIDs have been used for decades to treat symptoms of these viral infections, its the 101 for self-medication. Sure, but WO/2013/030058(Individual [DE]; March 7, 2013) claims that diclofenac has an actual prophylactic effect (specifically against influenza), and a therapeutic effect that is not related to its inhibition of prostaglandin biosynthesis and the resulting analgetic, antiphlogistic, and antipyretic effects. No molecular data are given in support of this claim, and the human use data are limited to case reports. The peer review literature does not appear to provide corresponding clues. But still – how about following this up?
Chloroquine And Chlorpromazine For Pulmonary Infection
Here is another well-known agent that, according to WO/2013/044871(Chinese Academy of Medical Sciences; Military Vetrinary Institute [CN]; April 4, 2013), prevents influenza virus infection: chlorpromazine, the first systematically used antipsychotic. Another “oldie,” chloroquine(the first synthesized antimalarial drug, dating back to World War II) is said to treat influenza. Here we have good in vivo data provided, and there is a solid background of earlier data to judge these claims against: chloroquine is being investigated for HIV and Chikungunya virus infection, and chlorpromazine is not only a multimodal receptor antagonist (it blocks dopamine, serotonin, histamin, alpha-adrenergic and muscarinic acetylcholine receptors, to name just some of its activities); but also an inhibitor of clathrin-mediated endocytosis – the typical viral entry mechanism. Note however that the influenza virus can bypass this mechanism (J Virol. 2002; 76(20):10455-64, here).
Oxymetazoline For Foot Neuroma And Tarsal Tunnel Syndrome
Foot neuroma results from a perineural fibroma (fibrous tissue formation around nerve tissue) in the intermetatarsal spaces. The resulting symptoms typically present as numbness, burning, tingling or sharp, shooting pain in the ball of the foot or between the toes. Tarsal tunnel syndrome results from the compression of the tibial nerve, and produces roughly similar symptoms. According to WO/2013/052770(Individual [US]; April 11, 2013) these nerve symptoms can be relieved by administering a vasoconstricting sympathomimetic drug (specifically, the a1-adrenergic agonist oxymetazoline, best known for its use as a decongestant in OTC nasal sprays for rhinitis) to the sole or heel, thereby relieving the irritation to the nerve caused by the strong arterial pulse. Case studies and a small clinical study with a 0.05% oxymetazoline cream are presented.
Bismuth Salts for Bloody Diarrhea
The haemolytic uremic syndrome (HUS) came to public attention in the course of a foodborne outbreak of bloody diarrhea caused by enterohemorrhagic E. coli (EHEC) strain O104:H4. The inventors of WO/2013/054148(Individuals [AR]; April 18, 2013) have found that ions, particularly Bi+3 ions, are effective in suppressing virulence factors of Shiga-toxigenic strains. Preferred formulations are suspensions of colloidal bismuth hydroxide gel (3 g of bismuth per 100 ml). To adults and children over 12 years, these can be administered in an amount ranging from about 30 to about 60 ml (half that dose for children under 12 years of age), every 4 – 6 hours. The MIC values for E. coli 0157:H7 were in the order of Bi+3 concentrations of 10 mg/ml. All that should not be terribly surprising to microbiologists: bismuth sulfite agar is the differential culture medium to isolate Salmonella ssp. from stool specimens because it suppresses the growth of Gram-positive bacteria – including E. coli.