Replies to post #46895 on Biotech Values

[gofishmarko]

Re : memantine for glaucoma

>>> I would ask my ophthalmologist his/her rationale for its use. <<<


It seems he recommended it to mouton because it works in monkeys. I don't know how I'd feel about that.

;)


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...

Arch Ophthalmol. 2006 Feb;124(2):217-25.

Memantine protects neurons from shrinkage in the lateral geniculate nucleus in experimental glaucoma.

Yucel YH, Gupta N, Zhang Q, Mizisin AP, Kalichman MW, Weinreb RN.
Department of Ophthalmology and Vision Sciences, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. [e-mail]

OBJECTIVE: To determine whether memantine as a treatment for glaucoma prevents neuron shrinkage in the lateral geniculate nucleus, the major target for retinal ganglion cells. METHODS: Sixteen monkeys with right-eye unilateral experimental glaucoma for 14 months were studied and treated with memantine (n = 9) or vehicle only (n = 7). Left lateral geniculate nucleus relay neurons (layers 1, 4, and 6) were examined following parvalbumin immunolabeling. Cell body cross-sectional areas and neuron numbers were assessed using unbiased methods. Memantine- and vehicle-treated glaucoma groups were compared using t tests and analysis of covariance. RESULTS: Compared with vehicle-treated animals, memantine-treated animals showed significantly less mean +/- SD neuron shrinkage in layers 1 (-4.0% +/- 13.9% vs 28.2% +/- 17.4%; P = .001) and 4 (24.9% +/- 10.0% vs 37.2% +/- 12.3%; P = .04). For layer 6, the difference was not statistically significant (34.2% +/- 10.1% vs 45.3% +/- 14.5%; P = .10). Analysis of covariance results showed significantly less neuron shrinkage in the memantine-treated group for layers 1, 4, and 6 (P < .001; P < .02; and P < .04, respectively). This difference was greatest in layer 1. In each of these layers, neuron numbers did not differ significantly between groups. CONCLUSION: Monkeys with glaucoma that were treated with memantine showed significantly less neuron shrinkage in the lateral geniculate nucleus than the vehicle-treated glaucoma group. CLINICAL RELEVANCE: The finding that memantine protects adult visual neurons from transsynaptic atrophy in experimental glaucoma could have therapeutic value. Currently, memantine is being tested in an ongoing clinical trial as a treatment for glaucoma.

[mouton29]

My doctor had mentioned the monkey results. I believe there is some evidence that Alphagan, one of the eyedrops I take, has some neuroprotective effect in rats -- I think they crush optic nerve cells with and without Alphagan. The monkey study seems a little stronger, although 8 treated monkeys is hardly definitive.

For me, the cost after insurance is $30/month, a sum I am willing to risk pending the results of the 5000 patient Allergan trial. I focused more on the side effect profile, and for me, there have been none. It is also very difficult for a layman to evaluate the plausibility of basic science arguments about blocking glutamate and calcium flows, etc.

Also, if specific proof of mechanism of action were required, I don't think any of the IOP lowering drugs would be approved. You will retort, at least those drugs have evidence of efficacy via randomized trials, which memantine does not yet. I do know that there is evidence that there is a "cascade effect," whereby dying ocular nerve cells sent a signal to other cells, which also start to die. That's not an explanation at all of why menantine might work, but it partly explains why neuroprotection is important.