NGX424

Trials for the new migraine drug, Tezampanel (NGX424), are moving quickly ahead.  So it’s time to catch up on what this drug is, and who it might help.

Tezampanel is based on an emerging understanding of the role of glutamate (an amino acid) in pain.  Targeting glutamate receptors (either through antagonists like Tezampanel or through modulators like ADX10059) is a new concept that may help not only those with migraine, but also muscle spasticity, fibromyalgia, arthritis, diabetic neuropathy, epilepsy, and neuropathic pain in general.  It may also suppress symptoms of opioid medication withdrawal.

Why target Glutamate?

Glutamate is a key neurotransmitter.  It’s called an excitatory neurotransmitter, and is the one most commonly found in your body.

Glutamate has a number of functions in your body, which may include to ability to learn and memorize, and the transmission of pain signals.

During certain stages of the pain chain-reaction, glutamate gets very busy sending signals.  In certain people with chronic pain especially, there may be too much glutamate, inducing more pain than should be necessary.

Researchers are actually getting very excited about levels of glutamate, because this may be the key to understanding the mysterious chronic pain in many people.  Could it be that some people’s chronic pain could be "seen" by the levels of glutamate?  Better yet, could the pain chain reaction be stopped or slowed by controlling glutamate?

Glutamate does have a role in migraine.  It’s present in the trigeminal nerve (where migraine pain often radiates from).  It plays a role in cortical spreading depression (a brain "storm" that is a major part of a migraine attack), and seems to be key in causing central sensitization, where certain neurons in the spinal cord become sensitized, possibly causing increasing chronic pain.  (more about what happens during a migraine attack)

Enter Tezampanel

Tezampanel (also called NGX424) is a drug being developed by TorreyPines Therapeutics, based on research done at Johns Hopkins University.  It’s unlike any other drug in what it does.  In scientific terms, Tezampanel is an ionotropic glutamate receptor antagonist that targets the AMPA and kainate sub-type receptors.  Glutamate receptors receive glutamate and become activated – this drug is designed to interrupt the process.

There are actually two drugs here being tested, but we’ll get to the second in a moment.  Tezampanel itself is injected, and was compared with injections of Imitrex (sumatriptan).  It was found to work as well as Imitrex.  Symptoms that Tezampanel seems to help with:

• pain (and excessive pain sensitivity)
• nausea
• sensitivity to light and sound
• allodynia (sensitive/painful areas on the skin)

Tezampanel and NGX426

Another related drug in an earlier stage of testing is NGX426.  This is a "prodrug" of Tezampanel, which means that it causes Tezampanel to be formed in the body.

NGX426 is an oral drug, not an injection.  Last month (February 2009) a Phase I trial was completed, and so far so good (read the results of the this early trial).  NGX426 seems to have promise for relieving pain in migraine.

Side effects?

When a new drug comes out, there is always hope that many patients suffering from the side effects of something else may be able to make the switch.  How is Tezampanel looking regarding side effects?

So far the side effects seem to be fairly minimal.  Common ones seem to be:

• pain at the injection site (of course this wouldn’t happen if you took NGX426 orally)
• dry mouth
• some other side effects in very few people may include dizziness and sleepiness

The next step

Tezampanel is heading into the last stages of testing.  NGX426 is farther behind, just heading into Phase II (of III).  TorreyPines Therapeutics is just putting together the funding it needs to carry out the next step.

Summary

Drugs coming out that are totally different than what has come before are especially interesting.  Not only may they help people who haven’t been helped, they may also lead to new treatments and breakthroughs.  When it comes to chronic pain, Tezampanel is one to watch.

From what we’ve seen so far, this drug may work well for some people who have been unable to take other types of migraine drugs due to side effects or other medical conditions.  It may also hold hope for those who have chronic pain conditions, including chronic migraine.

TorreyPines has more on Tezampanel and NGX426 here

Heads up from Ellen Schnakenberg