Cone Snail Venom: Medical Uses and Potential Benefits
What Are Cone Snails?
Cone snails are ocean predators with beautifully patterned shells. The snails produce a potent venom to paralyze their prey. The venom contains a complex mixture of substances that includes neurotoxins, which are chemicals that block the conduction of nerve impulses. At least one of these neurotoxins can relieve severe pain in humans. Researchers have also discovered that one species of cone snail produces a fast-acting form of insulin.
Scientists suspect that venom chemicals may be useful in many other ways besides the relief of pain. For example, specific chemicals may prevent epileptic seizures and lead to the creation of an improved treatment for diabetes. Researchers are also using the neurotoxins in the venom to learn about the functioning of our nervous system. These investigations may lead to the creation of new treatments for various diseases.
A Deadly Animal
There are more than 600 different species of cone snails, all belonging to the phylum Mollusca and the genus Conus. Most inhabit the warm water of tropical reefs. The snails have roughly cone-shaped shells, which gives them their name.
The Life of a Cone Snail
Cone snails use their venom to catch small fish, mollusks, and worms. Like other snails, cone snails move quite slowly. The exception to this rule is their equipment for catching prey, which moves impressively fast.
The snails have a tubular and extendable mouthpart called a proboscis. The mouth of a snail contains a radula, a ribbon-like structure that is covered with tiny teeth made of chitin. Cone snails have a modified tooth on their radula. The tooth extends out of the proboscis and stabs the prey like a hypodermic needle. The tooth is barbed and contains a hollow channel that conducts venom from a poison sac at its base. The venom is injected into the prey, immobilizing it. The tooth is then withdrawn as the prey is swallowed whole.
Cone snails have an eye on the end of two eye stalks, but they detect their prey by means of their siphon. This is a large tube that draws in sea water. The snail absorbs oxygen from the water. It also detects the presence of dissolved chemicals in the water, including those released by the prey. Cone snails often hide in the sediments of the ocean bottom with just their siphon protruding.
Venom of the Geography or Geographic Cone Snail
The geography or geographic cone snail is sometimes known as the cigarette cone snail. It's said that a person who has been poisoned by the animal's venom has time to smoke one cigarette before they die.
The smaller cone snails can give humans a painful sting but aren't dangerous. The bigger ones—which may be as long as nine inches—can be deadly for humans. They will attack to defend themselves as well as to catch their prey.
Cone snail venom contains a complex mixture of many different chemicals. There are thought to be at least fifty to a hundred biologically active compounds in the venom. There may be as many as two hundred compounds in some versions of the venom.
The venom contains conotoxins, also known as conopeptides, which are short chains of amino acids. Conotoxins quickly stop nerve impulses from passing between nerve cells or from passing from nerve cells to muscles. These actions cause paralysis in the snail's prey.
Medical Uses of the Venom
Research into the properties of cone snail venom is making some exciting discoveries. At least some conopeptides are able to relieve pain, which they sometimes do very effectively. One kind is already being used as an analgesic (pain reliever) in humans and others are being tested. There may be many other uses for the chemicals in medicine.
Conopeptides are proving helpful in a non-clinical context as well. Each type seems to work by a very specific mechanism in the nervous system. Researchers are learning more about how the nervous system works with the aid of conopeptides.
The venom of each species of cone snail contains its own unique mixture of chemicals, which increases the likelihood that some venom chemicals may be useful to humans.
Ziconotide for Pain Relief
After studying a conopeptide in the venom of a cone snail known as Conus magus, researchers have made a synthetic version of the peptide. The artificial chemical, called ziconotide, has some useful properties. It has been approved as a medication in the United States by the FDA (Food and Drug Administration) and is in current use as an analgesic.
Ziconotide can be very effective at relieving pain, but its effects are variable. Some people say that the medication has been a wonderful help for them, some say that it produces only minor or partial pain relief, and others say that its benefits aren't worth the side effects that they experience.
Ziconotide is not addictive. In addition, it doesn't cause the development of tolerance in a patient. Tolerance is a state in which a medication that was once effective no longer works. The medication is sold under the brand name of Prialt.
Ziconotide is used after other analgesics have been tried and have failed to work. It is prescribed only for people who are suffering from intense and prolonged pain, such as the pain that may be experienced by people with certain types of cancer or for people experiencing neuropathic pain.
How Does Ziconotide Work?
Ziconotide works by inhibiting the transmission of nerve impulses at synapses. A synapse is the region where the end of one neuron or nerve cell comes very close to the start of another one.
Normally, when a excitatory nerve impulse reaches the end of a neuron, it stimulates the release of a chemical called a neurotransmitter. This chemical travels across the tiny gap between neurons, binds to a receptor on the second neuron, and then stimulates a new nerve impulse. Ziconotide inhibits the release of the neurotransmitter.
Structure of a Synapse
Potential Drawbacks and Side Effects of Ziconotide Use
Ziconotide does have some drawbacks. It must be injected into the cerebrospinal fluid in the spinal cord in order to work because it can't cross the blood-brain barrier. Researchers are trying to find a way to overcome this barrier. The current means of injection into a patient is known as an intrathecal injection. It's generally performed via an infusion pump and a catheter, which must be implanted. Although the implantation may sound unpleasant, it may be very worthwhile for someone who is experiencing chronic and life-altering pain that can't be relieved by other methods.
A major advantage of injecting the drug directly into the nervous system is that the minimum amount required to relieve pain can be used. This is important because ziconotide sometimes produces significant side effects. One possible side effect of the medication is a mood change, including depression. Other possible effects are confusion, memory impairment, and hallucinations. The incidence of problems increases as dose increases.
A patient taking ziconotide must be closely monitored. The patient and people close to them should note any problems that develop. Fortunately, ziconotide use can be stopped abruptly without the patient experiencing withdrawal symptoms, allowing the side effects to disappear. It would be wonderful if researchers could discover how to block the unwanted effects of the medication.
A Weird Animal
Insulin in Cone Snail Venom
Another exciting discovery about the venom of at least one cone snail—Conus geographus—is that it contains a type of insulin, the hormone that diabetics lack. In addition, this insulin can bind to the human insulin receptor on the membrane of cells.
In humans, insulin stimulates the transfer of glucose (a type of sugar) out of the blood and into the cells, which use it to produce energy. As a result, the blood sugar level is lowered.
Cone snail insulin is fast acting. Within minutes of receiving the insulin injection from the snail, the prey develops very low blood sugar, experiences hypoglycemic shock, and becomes sedated. This condition makes it easy for the snail to catch the prey.
The snail insulin is not identical to the human type, but it's similar enough that its discovery has excited scientists. By studying the animal's insulin, they may be able to develop a better form of insulin for humans.
Assorted ShellsClick thumbnail to view full-size
Other Potentially Helpful Chemicals in Cone Snail Venom
Conantokins are a family of conopeptides found in cone snail venom. The best known member of the family is conantokin-G from the geography cone snail. The chemicals are sometimes called "sleeper peptides" because when they are injected into the brain of young mice they trigger sleep.
Researchers who are studying conantokins have discovered that they can block seizures in mice. The peptides work by a mechanism that may be helpful for humans with epilepsy. Their ability to block specific chemical receptors in the nervous system may have benefits beyond the treatment of epilepsy.
As is the case with some other cone snail chemicals, researchers have produced synthetic molecules based on the natural ones in order to improve the properties of conantokins for medical use. The chemicals are still being explored by researchers and are not yet available as medications. They could be very helpful in the future, however.
Scientists are using these neurotoxins, some powerful enough to kill people, as the basis for research into the development of life-saving drugs for medical conditions including intense chronic pain, epilepsy, asthma and multiple sclerosis.— University of York
Population Status of Cone Snails
Unfortunately, some cone snail populations are in trouble. The snails are dying due to coastal development, ocean pollution, destructive fishing methods, and climate change. In addition, they are collected and killed for their beautiful shells, which are popular as decorations. Some shells are sold for thousands of dollars.
Researchers at the University of York in the UnIted Kingdom have completed a population assessment for all of the 632 known cone snail species. The International Union for the Conservation of Nature (IUCN) assigns organisms to a "Red List" category according to their population status with respect to extinction. As a result of the cone snail survey, 67 species have been placed in the endangered, vulnerable, or near threatened categories in the Red List. The loss of the snails and their neurotoxins could be unfortunate for humans.
It's sad when any species is threatened with extinction, but in this case the situation could hurt humans, too. What is especially worrying is that there are almost no conservation efforts for cone snails. The studies of the complex venoms of cone snails are slowly yielding wonderful possibilies for new medications. It would be very sad to lose the chance of improving treatment for pain and perhaps of discovering new treatments for diseases.
© 2014 Linda Crampton