We conclude our discussion of drug repurposing patents published in June 2014 with patent applications for repurposing candidates that could not be further apart in price (GM-CSF and Aspirin); an immunomodulatory dipeptide; and yet another NSAID for Alzheimer’s disease.
For those who can and will take a few days off — enjoy!
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A Dipeptide for Atopic Eczema and Psoriasis
Pidotimodis a synthetic immunomodulatory dipeptide mimetic that is available in Asian, Central American, and European countries (e.g., Polichem’s Imunorix®), primarily to treat recurrent respiratory infections in children (JBiol Regul Homeost Agents 2013; 27(1): 253-8, hereand Arzneimittelforschung 1994; 44(12A): 1525-9, here). Contrary to their expressed expectations that pidotimod might be detrimental in conditions of a selectively overactive immune system, the inventors of WO/2014/094839and WO/2014/094840(Polichem [LU]; June 26, 2014) have found that it reduced skin lesions of atopic dermatitis and psoriasis when applied topically at 5-10% (w/w) using an oil-in-water cream matrix or gels. Data from two five-patient pilot study are presented.
GM-CSF for Chronic Sinusitis
This is the actual title of WO/2014/096032(Trifoilium [DK]; June 26, 2014) and that made us wonder — who would consider using a recombinant colony-stimulating factor, priced at about dollar per microgram, for nasal congestion? Actually, it is not about the sniffles but about nasal and/or paranasal sinus polyps which – while not dangerous in itself – can reduce the quality of life sufficiently to require repeated surgery. Apart from its hemopoietic growth and differentiation stimulating activity, GM-CSFfunctions especially as a proinflammatory cytokine; one would not normally think of using it on inflamed and hypertrophic respiratory epithelium which itself contains and secretes GM-CSF (Rev Laryngol Otol Rhinol (Bord). 2009; 130(3): 163-7, here). But apparently, when applied to the “air side” of the mucous barrier (i.e., the surface of the nasal or paranasal sinus epithelium) using positive airway pressure, GM-CSF has a correcting effect on the T helper cell inflammatory pattern, inducing a shift from TH2 to TH1 cells. However, the price problem remains — the preferred dose, to be applied at least once daily for several days, appears to be 300 µg. On the other hand, surgery is not for free either. If this could be a practicable alternate use for Sanofi’s Leukine® (sargramostim) or several related biotech products that are normally used to speed neutrophil recovery after bone marrow ablation, or during chemotherapy for acute myeloid leukemia, remains to be seen.
ASS for Diabetic Wounds
Now, just for contrast, what about repurposing a drug that is really cheap — acetylsalicylic acid, for example? This is what WO/2014/096697(Laboratories Urgo & INSERM [FR]; June 26, 2014)proposes in the context of treating chronic diabetic ulcers. The use of oral ASS in this context is part of the newest Dutch treatment guidelines: “When the ulcer fails to heal the use of oral aspirin … can be considered as an adjunct” (Phlebology2014; 29(1 suppl): 153-6, here), and Teikoku Seiyaku’s EP-784975claims topical ASS for pressure ulcers; but the first-mentioned use is systemic and the second one targets bedsores, not diabetic wounds. This could make Urgo’s claims novel, even if inventiveness might lack.
Another NSAID for Alzheimer’s Disease
“Not again!” – you might think reading this headline; non-steroidal anti-inflammatory drugs have been investigated as potential Alzheimer drugs since the 1990s, and all have failed in therapeutic trials — although epidemiologic evidence suggests that they might have preventive effects, at least in subgroups of patients. WO/2014/100601(Govt. of Rhode Island [US]; June 26, 2014) puts emphasis on the effect of tolfenamic acid as a promotor of degradation for the transcription factor Sp1. This protein negatively modulates not only the expression of APP (the gene coding for the amyloid precursor protein) but it also downregulates of tau protein and CDK5. Furthermore, Sp1 levels were found to be elevated in the frontal cortex of Alzheimer patients as well as in transgenic animals that develop AD-like pathology. Parameters of learning and memory were improved in the hAPP YAC transgenic mouse model. – Note that the NSAID, R-flurbiprofen improves tau, but not Aβ, pathology in such models (Brain Res. 2013; 1541: 115-27, here). – This inventor team has published several papers in this context, Neuropharmacology 2014; 79: 596-602 (here) being the most recent one.