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Thank you all so much for your attention in 2012! This year is now in the history books and certainly some will be happier to see it there than others… But it was a great year for H.M. Pharma Consultancy! And we are particularly happy to show you that this blog has begun to attract some attention, perhaps even to make an impact. The year-over-year development of the pageview statistics indicate as much.
Below are four brief discussions of drug repurposing patents, published just before the holidays. Please attribute to H.M. Pharma Consultancy when citing from this post.
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A Repurposed Drug For An Ultra-Rare X-Linked Disease
In boys affected withAllan-Herndon-Dudley syndromethe SLC16A2gene, coding for the triiodothyronine (T3) transporter protein and also known as MCT8, has a loss-of function mutation; T3 is not available to nerve cells in sufficient amounts. Normal brain development is disrupted while increased T3 levels exert organ toxicity. Only about 25 families suffering from this type of mental retardation with muscle hypotonia have been documented worldwide. In what is probably not very far-fetched but might be a novel use for a known drug, WO/2012/171065(Individual inventor [AU]; Dec. 20, 2012)claims ionotropic cardiotonic analog of L-thyroxine. 3,5-diiodothyropropionic acid (DITPA) as a treatment.Oral doses of 0.5-1.5 mg/kg/day are suggested, without supporting biological data. The International Search Report raises many X-class critical objections. – DITPA has some limited use in heart failure, and because of its actions at liver thyroid hormone receptors ithas also been investigated for hypercholesterolemia (NCT00311987, Johns Hopkins University).
A Third Chance For A Twice-Failed Drug Candidate?
In 2006 Merck KGaA discontinued the development of sarizotan(a 5-HT1a receptor agonist and dopamine D3/D4 receptor ligand) for L-dopa-induced dyskinesia in Parkinson’s disease; it was one of the frequent late-stage clinical failures that mainly teach that – for a variety of reasons, and not always easily explicable – even good Phase II data might be misleading. Some years before that, Merck hat investigated sarizotan for schizophrenia — also no luck. In 2011, Newron Pharmaceuticals licensed the program but did not disclose its intentions. Only a few months later WO/2012/171653(Merz Pharma [DE]; Dec. 20, 2012) was filed claiming sarizotan as a drug for attention deficit disorder, with recommended doses of about 1 mg/day for patients weighing 30 kg and above, and between about 0.5 mg and about 0.75 mg/day for children weighing 30 kg or less. Sarizotan reduced impulsivity in the juvenile rat T-maze paradigm similar to stimulant drugs (methylphenidate, D-amphetamine) and noradrenaline reuptake inhibitors (desipramine, atomoxetine). In vitro results revealed sarizotan to be a full agonist (EC50 =150 nM) and a positive allosteric modulator (inflection point at 90 nM) at the 5-HT7 receptor.
A Nasally Administered Abortion Drug For Assisted Reproduction
Everyone recognizes the competitive progesterone receptor inhibitor mifepristone(RU486) as the prototypical abortion-inducing drug, but it also been investigated in women undergoing Controlled Ovarian Hyperstimulation (COH) as part of assisted reproduction. In this condition an early spontaneous gonadotrophin surge may cause an early release and loss of the oocytes, and – as published clinical studies have shown – this is preventable by mifepristone. However, these studies also showed that the therapeutic window defined by the antifolliculogenetic effects of mifepristone is extremely narrow, annihilating clinical applicability. WO/2012/171793(Parthenogen sagl [CH]; Dec. 20, 2012) claims that the rate of mifepristone bioavailable at hypothalamic binding sites can be increased at the expense of the rate reaching the circulation by administering mifepristone by the nasal route. In the proposed clinical study the majority of patients should not need luteinizing hormone supplementation in parallel to FSH administration; the non-desensitized pituitary gland will be able to release LH pulses with the appropriate frequency, amplitude and LH isoform composition.
Mecamylamine For Rabies
We admit to having lost count of the repurposing patents centered on the old nicotinc acetylcholine receptor blocker mecamylamineand we certainly don’t want to bore you, but WO/2012/172100(Institut Pasteur et al. [FR]; Dec. 20, 2012) certainly is something unusual in this respect. At 2 mg/kg i.p. given to mice 5 days after infection with the rabies virus, mecamylamine drastically decreased markers of cholinergic activation in the spinal cord and brain. Mecamylamine also prevented RABV-mediated spleen atrophy and disappearance of specific subsets of immune cells, maintained cerebral expression of neuronal nitric oxide synthase, triggered clearance of the rabies virus from the brain and protected mice against rabies death. It offered no protection when injected one day after infection.