Late March and early April have not exactly presented us with an abundance of patent applications clearly related to drug repurposing… but the last two rounds, on April 12 and 19, have yielded four: an antiepileptic (valproic acid) that lets your nails grow; a rosacea treatment combining a glaucoma drug and a nasal decongestant; an erectile impotence drug (Bayer’s vardenafil) for motor neuron disease; and classical “benzos” for autoimmune diabetes. – If you want to know more about our patent-supported drug repurposing knowledgebase, please contact H.M. Pharma Consultancy at office@hmpharmacon.com. – Forward the patentome!
Valproate for Better Nail Growth
All anticonvulsants are teratogenic to some degree, and all have side effects. For sodium valproatethere have been occasional reports of negative effects on finger and toe nails, from apparently harmless yellow pigmentation to complete destruction, through generalized onycholysis (Grech & Vella, Eur Neurol.1999; 42(1):64-5, PubMed) or onychomadesis(Poretti et al., Pediatr Dermatol.2009; 26(6):749-50; PubMed). With its claims for valproate as a promoter of nail growth, WO/2012/047007(AmorePacific [KR]; April 12, 2012)has to be considered paradoxical. But if valproate can induce hair regeneration (EP-2431031and Lee et al., PLoS One2012; 7(4): e34152; see here), with a Phase II clinical study (NCT01548066) by Seoul National University Hospital ongoing, why not nails? The rationale is that valproate inhibits GSK-3β. The application would be topical, which should render the side effect profile of valproate all but irrelevant.
Glaucoma Drug + Decogestant = New Treatment for Rosacea
Rosacea is not a dangerous disease in itself, but the severe facial erythema and telangiectasia (visible red lines due to abnormal dilatation of capillary vessels and arterioles), as well as disfiguring dermatological consequences of the more severe forms, can be socially devastating. (See DelRosso, J Clin Aesthet Dermatol. 2012; 5(3):16-25and 26-36). The role of alpha adrenoceptors in the vascular symptoms of rosacea is well known, providing the pharmacological rationale for WO/2012/047645(Galderma [US]; April 12, 2012) to claim the combined use of two adrenergic agonists – the glaucoma drug brimonidine and the decongestant oxymetazoline. Positive data from a Phase II clinical trial for a 0.5% topical gel formulation of brimonidine alone (see Galderma’s WO/2012/001064) have just been published (Fowler et al., Br J Dermatol. 2012; 166(3):633-4; PubMed). Oxymetazoline has also been claimed for treating the erythema of rosacea, in US2005165079A1(now owned by Allergan).
Yet Again a New Use for Vardenafil
Insulin-like growth factors act as neurotrophic factors in amyotrophic lateral sclerosis, and the IGF-II receptor is upregulated in this condition (Dagvajantsan et al., Tohoku J Exp Med. 2008; 214(4):303-10; PubMed). WO/2012/048330(McLean Hospital [US]; April 12, 2012) takes a logical step in claiming dozens of compounds that were found enhance the expression of IGF-II, preferably vardenafil (which upregulates IGF-II mRNA 6.5-fold and IGF-II protein 1.6-fold in primary spinal cord cultures from embryonic mice) and the old antihypertensive drug guanabenz, for various motor neuron diseases. In a luciferase reporter assay screen for inducers of IGF-II promoter activation, vardfenafil had performed best. A protocol for an in vivo study in wildtype or superoxide dismutase-1 transgenic rodents is outlined, with no results provided.
Sedatives for Diabetes
In WO/2012/050907(University of California [US]; April 19, 2012), the more extensive companion patent to a 2011 peer review paper (Tian et al., Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PLoS One 2011; 6(9):e25338; see here), the inventors claim not only GABA but a broad range of GABA receptor agonist drugs (essentially all established benzodiazepines, thienodiazepines, and dialkylphenols with this type of activity) to increase glucose tolerance and insulin sensitivity in patients at risk of developing type I diabetes. Various claims related to islet cell transplant survival, other autoimmune conditions and neuropsychiatric disorders are thrown in for good measure. This exploits the finding that GABA can modulate cytokine secretion, cell proliferation, and even cell migration (Jin et al., Amino Acids2011; PubMed). Of course these drugs have all been designed to cross the blood-brain barrier to act as anxiolytics at low doses, and the doses required for immune modulation would very likely go along with strong sedation.