Inosine and strokes.

[Frank E]

Is Inosine licenced by the MHRA for stroke treatment in an acute setting?


I could only see reference to Inosine Pranobex (Inosine Acedoben Dimepranol) an anti Viral for treatment of HSV, though I have an old BNF.

[melon]

It's not in the latest BNF and I've never heard of it being used for stroke. As far as I know, it's actually only in the in vitro stages of research. It will likely be a few more years before it becomes available for use 'off-label' in humans and probably a while longer before it gets licensed.

Prog Brain Res. 2002;137:389-99.

Inosine stimulates axon growth in vitro and in the adult CNS.
Benowitz LI, Goldberg DE, Irwin N.

Unlike mammals, lower vertebrates can regenerate their optic nerves and certain other CNS pathways throughout life. To identify the molecular bases of this phenomenon, we developed a cell culture model and found that goldfish retinal ganglion cells will regenerate their axons in response to the purine nucleoside inosine. Inosine acts through a direct intracellular mechanism and induces many of the changes in gene expression that underlie regenerative growth in vivo, e.g., upregulation of GAP-43, T alpha-1 tubulin, and the cell-adhesion molecule, L1. N-kinase, a 47-49-kDa serine-threonine kinase, may mediate the effects of inosine and serve as part of the modular signal transduction pathway that controls axon growth. In vivo, inosine stimulates extensive axon growth in the mature rat corticospinal tract. Following unilateral transection of the corticospinal tract, inosine applied to the intact sensorimotor cortex stimulated layer 5 pyramidal cells to upregulate GAP-43 expression and to sprout axon collaterals. These collaterals crossed the midline at the level of the cervical enlargement and reinnervated regions whose normal connections had been served. Further understanding of the molecular changes that lie upstream and downstream of N-kinase may lead to new insights into the control of axon growth and to novel methods to improve functional outcome in patients with CNS injury.

J Neurosci. 2009 Jun 24;29(25):8187-97.

Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb.
Zai L, Ferrari C, Subbaiah S, Havton LA, Coppola G, Strittmatter S, Irwin N, Geschwind D, Benowitz LI.

Recovery after stroke and other types of brain injury is restricted in part by the limited ability of undamaged neurons to form compensatory connections. Inosine, a naturally occurring purine nucleoside, stimulates neurons to extend axons in culture and, in vivo, enhances the ability of undamaged neurons to form axon collaterals after brain damage. The molecular changes induced by inosine are unknown, as is the ability of inosine to restore complex functions associated with a specific cortical area. Using a unilateral injury model limited to the sensorimotor cortex, we show that inosine triples the number of corticospinal tract axons that project from the unaffected hemisphere and form synaptic bouton-like structures in the denervated half of the spinal cord. These changes correlate with improved recovery in animals' ability to grasp and consume food pellets with the affected forepaw. Studies using laser-capture microdissection and microarray analysis show that inosine profoundly affects gene expression in corticospinal neurons contralateral to the injury. Inosine attenuates transcriptional changes caused by the stroke, while upregulating the expression of genes associated with axon growth and the complement cascade. Thus, inosine alters gene expression in neurons contralateral to a stroke, enhances the ability of these neurons to form connections on the denervated side of the spinal cord, and improves performance with the impaired limb.