Cocaine overdoses can have a devastating impact, causing kidney failure, strokes and even death. Now scientists are on the verge of creating an antidote that could reverse the damaging effects in accident and emergency rooms.
Scientists at The Scripps Research Institute have shown that an injectable solution can protect mice from an otherwise lethal overdose of the Class A drug.
If they can find a way to produce the solution cheaply and in large quantities they said there was no reason why it couldn’t go forward for human clinical trials.
‘This would be the first specific antidote for cocaine toxicity,’ said study author Dr Kim Janda.
‘It’s a human antibody so it should be relatively safe, it has a superior affinity for cocaine, and we examined it in a cocaine overdose model that mirrors a real-life scenario,’ he said.
Cocaine is involved in more than 400,000 emergency-room visits and about 5,000 overdose deaths each year in the United States. In 2008 there were 235 deaths linked to cocaine abuse in England and Wales.
In 2005, Dr Janda reported that injections of a mouse-derived anti-cocaine antibody, GNC92H2, could keep mice alive despite cocaine doses that killed unprotected mice.
The passive vaccine worked by crossing the blood-brain barrier, which caused the cocaine molecules to diffuse out of the brain tissue. At the same time it reduced the drug’s effects on the heart and nearby organs.
However, mouse antibodies are not ideal for use in humans as human immune systems eventually develop a reaction against them.
In the new study, Janda and Dr Jennifer Treweek, used a genetically engineered mouse that can produce fully human antibodies against cocaine molecules.
The best of these antibodies, GNCgzk, showed ten times the cocaine-binding affinity of GNC92H2, the molecule used in the 2005 study.
In a test that simulated a real-life emergency situation, mice were first given a cocaine overdose, and three minutes later were infused with GNCgzk.
About half of untreated mice were killed by such a dose. While GNC92H2 reduced that rate to about 28 per cent, the new GNCgzk antibodies reduced the mortality rate further, to 20 per cent.
More strikingly, a stripped-down version of GNCgzk - which contained only the antibody’s cocaine-binding segments - reduced the mortality to zero, as well as significantly reducing overdose signs such as seizures.
‘There was a reversal of the signs of cocaine toxicity within seconds of the injection,’ said Dr Treweek.
Dr Janda said the treatment could be useful not only in reducing the immediate effects of an overdose, but also in preventing near-term relapses.
‘A lot of people that overdose end up going back to the drug rather quickly,’ Dr Janda said, ‘but this antibody would stay in their circulation for a few weeks at least, and during that time the drug wouldn’t have an effect on them.’
Likewise, this antibody could be administered to patients in addiction recovery or detox programs as a treatment to supplement other medications, such as antidepressants and counseling.
An acute relapse during this recovery period would be immediately nullified by the antibody dose that is already in circulation.
The findings were reported in the journal Molecular Pharmaceutics.
Source: Dailymail.co.uk
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