FDA-approved anti-epileptic drug perampanel is able to prevent the progression of ALS

[GregK]

For sporadic ALS.

Experimental results showed the drug was able to prevent the death of motor neurons and normalized the localization of TDP-43 with the cells. Moreover, long-term administration of the drug in mice also led to visible improvement of motor dysfunction in the treated mice, as compared to the control mice.

https://alsnewstoday.com/2016/07/08...ology-motor-function-sporadic-als-model-mice/

 

[Bob R]

So it's already found safe. There should be a quick 6 month study for efficacy, then it should be prescribed off label if the FDA doesn't act. Yeah, that may happen.

 

[Nikki J]

There are a lot of things that help mice and not us. The antiepileptics are a promising area. Retigabine is an example that showed benefit in IPS cells. Off label can happen if your doctor is willing but This seems not ready for prime time?

 

[KimT]

http://www.medscape.com/viewarticle/815421_5

My doctor will prescribe anything I ask for off-label. I print out everything I can find and he said he will Rx it.

 

[lgelb]

Ummm... a quick 6-month study for efficacy in a disease it hasn't been studied in at all? How will you find doses, test for toxicity (new indication, very different people), determine efficacy, benefit to risk ratio? This drug has a black box warning (that's the strongest type the FDA requires) for neuropsych issues in a dz where cog impairment/mood changes are increasingly recognized.

And no, the mice haven't matched up of late, nor the glutamate theory (remember gabapentin? memantine?)

You may have seen mention of a predecessor compound in this class, talampanel, which was tested in ALS and did not prove out. It had earlier indications as well, but some of the non-mice animal testing revealed significant risks. The company that held rights to it originally had stopped development years before the ALS trial.

The one is supposedly more selective, FWIW, but folks, it's a centrally acting drug. We're talking about your brain. On a new drug whose putative efficacy results rest with mice that have proven poor disease models, and in a class littered with rejects and disappointment.

It may be awesome. It may be the best thing since...anything in ALS. But esp. at the doses used in epilepsy, it's not something to take lightly.

 

[Bob R]

I agree the side effects are pretty scary. But if the options are certain and horrible death or possible side effects, well....I believe ALS has not one cause, but many. And that does not bode well for a single cure. What we may wind up with are a number of drugs, some will work for some and others for others. That's why efficacy is so iffy. If this particular drug works for say, 10 %f the participants, it should be put on a right to try list.

And I'm not sure 6 months is so quick for our disease.

 

[GregK]

From:Perampanel: A Selective AMPA Antagonist for Treating Seizures

Perampanel is the first selective noncompetitive AMPA receptor antagonist to be successfully developed to treat epilepsy. The drug was recently approved in the United States and Europe to treat localization-related seizures in patients ≥12 years old (1, 2). In the past, glutamate receptor antagonists were evaluated to treat a variety of neurologic disorders, including hypoxic injury, amyotrophic lateral sclerosis, Parkinson disease, and epilepsy. NMDA receptor antagonists, however, produced unacceptable CNS depression and talampanel, a selective noncompetitive AMPA antagonist, was not developed after an initial promising epilepsy trial and limited effects in ALS and glioma trials (3).

 

[bear1973]

It may be awesome. It may be the best thing since...anything in ALS

....that for me is enough to try it....starting at the smallest dose. Wikipedia says:

"In clinical trials, perampanel was generally well tolerated although the incidence of adverse events increased in a dose-dependent fashion. There was no increase in serious adverse events compared with placebo"

I might skip it for a more minor, non-life threatening condition...but with ALS everything for me is different - I am willing to do things I wouldn't normally do.

 

[Nikki J]

I understand what you are saying about nothing to lose. You should know though that even with a drug that has been approved for other indications we don't know how it affects humans with ALS. There is always a possibility that it could make ALS worse.

My sister took Dex ( for those who do not know it was a drug that had a very promising phase 2 and we all hoped for quick approval after phase 3. And then it failed phase 3. ). When my sister stopped taking it she realized it had been making her worse and part of what she took to be progression got a little better for a while.

 

[bear1973]

That is a well-heard point Nikki and I guess it depends on each person individually. For example, a person well into the disease who has been much affected physically and mentally might be more willing to try an off-label drug than someone newly diagnosed with already slow progression and much mobility.