Inducing endogenous production of BDNF
Myogane is a novel, orally active, nonpeptide compound that can cross the bloodbrain barrier, can distribute to ocular tissue,
and is able to induce the production and release of endogenous neurotrophic factors, as demonstrated in a number of studies
both in vitro and in vivo. In vitro, it has been demonstrated that the compound can increase BDNF protein and mRNA expression and may also be able to modulate
more than one neurotrophic pathway in addition to stimulating the BDNFmediated pathway, therefore producing additional benefits.
This hypothesis is supported by the finding that an epimer of the compound has been shown to induce both BDNF and GDNF production
in vitro and in vivo.15,16
Figure 1: Effect of post-glutamate treatment with Myogane and BDNF on glutamate-induced neuronal damage in rat retinal ganglion
cells (neuronal survival as a percentage of control; mean ± s.e.mean, n=16-18;****=p<0.001 compared to control, ++++=p<0.001,
*=p<0.05 compared to glutamate alone).
Myogane has already been shown to reduce and reverse glutamateinduced neurodegeneration in cultured rat retinal ganglion cells
(Figure 1) and is currently being evaluated in a rat ocular hypertension model of glaucoma (intracameral injection of latex
microspheres) the results of which will be reported in Q1 of 2012. It has already completed safety pharmacology and longterm
toxicology studies and has been evaluated in two Phase I clinical studies and is therefore ready to be evaluated in longer
term clinical studies should the preclinical efficacy study suggest that Myogane has the potential to treat glaucoma. The
next step would be for Phytopharm, or a development partner, to evaluate Myogane in a randomized, doubleblind, placebo controlled
study in subjects with demonstrable progression of glaucoma, despite optimized management of their IOP.
If efficacy can be demonstrated then Myogane should be effective in treating all glaucoma sufferers. This compound may have
particular utility in younger patients who demonstrate disease progression despite optimized IOP reduction, as these patients
are most likely to suffer a loss of vision and that this loss will occur earlier in their life.
The loss of sight at any age is associated with a significant handicap, a reduction in quality of life and substantial economic
direct and indirect costs. Consequently, there is a strong pharmacoeconomic argument for neuroprotective agents, such as Myogane,
that delay or prevent loss of vision.
*Myogane is a registered trademark of Phytopharm plc.
Dr Patrick A. Howson is Head of Preclinical Sciences at Phytopharm plc, Huntingdon, UK. He may be reached by E-mail: email@example.com
Dr Howson works for the company that is developing Myogane.