The inaugural “zero” issue of the Mary Ann Liebert, Inc. peer review journal Drug Repurposing, Rescue and Repositioninghas been much applauded and we are now putting out a call for manuscripts to be published in the first regular issue 1(1), due in early 2015. We will need your contributions by December 26, 2014 at the latest.
Meanwhile, be invited to the first part of our PCT drug repurposing patent review for September 2014! And of course, please join our LinkedIn discussion group, Drug repurposing – reprofiling – repositioning (currently 647 members).
For your consulting needs we are available as per below.
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Yet more Applications for Probucol
Probucolhas powerful anti-oxidant and anti-inflammatory properties that reduce atherosclerosis and restenosis; among many other activities it induces heme oxygenase-1 (Curr Opin Lipidol. 2009; 20(3): 227-35, here) and NAD(P)H:quinone reductase (Pharmacol Toxicol. 2003; 93(6): 259-63, here). It is sold, as Lorelco®et al., and used mainly for familial hypercholesterinemia. Its cardiovascular risks (Qt interval prolongation and HDL cholesterol reduction) preclude its use in primary prevention (Drugs 1989; 37(6): 761-800, here). For almost three decades probucol has also been proposed as an addition to antidiabetic therapy that would protect pancreatic beta-cells and reduce cardiovascular complications, and as a protectant in cardiotoxic chemotherapy. WO/2014/131360 (Shanghai Institute of Materia Medica [CN]; Sept. 4, 2014) now claims that probucol can inhibit tumor metastasis, especially lung metastasis of breast cancer. The companion peer review paper, which presents probucol formulations using nanosome technology, is Small2014 Jun 16 (here).
Piroxicam for Cytomegalovirus Infection
While there are several reports in the peer review and patent literature that document the utility of NASAIDs, including piroxicam, to treat inflammation and pain from various herpesviridaeinfections, the inventors’ WO/2011/124366had claimed actual treatment (and prophylaxis) of herpes simplex and varicella zoster infection with piroxicam. But, as they point out in their follow-up application WO/2014/135638 (Deavalorum [DE]; Sept. 12, 2014), these are alpha-herpesvirdae while cytomegalovirus is a beta-herpesvirus, in a different subfamily. A 30-second incubation of a CMV suspension with a commercial piroxicam injection solution (20 mg/ml) produced a 4.83 log reduction in viable CMV particles, indicating suitability for topical application.
An Old Antihypertensive for Multiple Sclerosis…
Guanabenzis an α2 adenergic receptor agonist and a first-generation antihypertensive drug, compromised by the drowsiness it induces. Recent research indicates that it enhances the unfolded protein response (by selectively inhibiting GADD34-mediated dephosphorylation of eIF2α), potentially making it a drug for conditions involving endoplasmic reticulum stress such as amyotrophic lateral sclerosis (Neurobiol Dis. 2014; 71:317-24, here). While ALS is distinct from MS, this mechanism has a quite immediate and direct connection to this and other demyelinating diseases, where cells of the oligodendrocytelineage (which provide the myelin sheath in the CNS) suffer damage due to inflammatory insult. Stimulation of β2 adrenergic receptors on astrocytes (causing activation of protein kinase A) has been suggested as a therapeutic approach in MS (Neurochem Int. 2010; 57(4): 446-50, here). And indeed, as inventors of WO/2014/138298 (Chicago University [US]; Sept. 12, 2014) found, guanabenz also works in the experimental autoimmune encephalitis mouse model, the standard testing paradigm for MS drugs. The suggested dose for humans is 64 mg/day.
…And an Old Beta Blocker for ALS
Oxprenololis a non-selective beta blocker with some intrinsic sympathomimetic activity (i.e., it can also show beta agonism, depending on the concentration of the agent), marketed under several trade names but probably best known as Trasicor®and Coretal®. It is quite lipophilic and crosses the blood-brain barrier more easily than other drugs of its type. It is also chiral. (S)(–)-oxprenolol, the subject of WO/2014/138814 (Individual inventors [DE/AU]; Sept. 18, 2014), was slightly more effective than the (R)(+) isomer in promoting survival of male or female animals in an ALS mouse model at dosages of 10 or 20 mg/kg/day. The same effect was seen with disease progression in all stages (from score 1 to score 2, and from score 2 to score 3). Propranolol was also effective.
An Anticoagulant for Dry Eye and Corneal Ulcers
Dipyramidole(originally Persantine®, but long generic; sold as Aggrenox®in a fixed combination with acetylsalicylic acid by Boehringer Ingelheim) is a phosphodiesterase and adenosine uptake inhibitor with platelet inhibiting and vasodilatory effects. According to WO/2014/141079 (Remedeye [US]; Sept. 18, 2014) it is good for treating dry eye and its complications, but also for corneal ulcers and pterygiumresulting from infections or eye trauma. Dipyridamole eye drops or ointment (preferably 10 µM) were administered to the eyes of subjects suffering from Sjögren’s-related dry eye, non-specific keratitis, or allergic conjunctivitis once to three times per day. According to the case reports, relief became complete within 2-7 days. Even with keratoconus, once to twice daily administration for three months led to an improvement in astigmatism that enabled lowering of cylinder by a quarter to half a number in two subjects. – The inventor, Moshe Rogosnitzky, has a track record in drug repurposing; he also holds intellectual property concerning the use of low-dose naltrexone for inflammatory bowel disease.