Researching snake venom in hope of finding life-saving treatments


More and more snakes are moving into towns and cities due to urbanisation, like this cobra found in a car engine in Beaufort, Sabah. — Photos: Filepic

According to the World Health Organization (WHO), five million snakebites occur around the world every year.

Of this number, up to 2.7 million cases involve envenoming, where the snake’s venom is injected into the victim.

Death is the worst outcome of snakebite envenoming.

However, some who survive the venom may lose their limbs or experience permanent disabilities such as paralysis, bleeding disorders, irreversible kidney failure and tissue damage.

Recognising the severity of snakebite envenoming as a public health issue, WHO added it to its priority list of neglected tropical diseases (NTD) in June 2017.

Through its new 2021-2030 roadmap for NTDs, the international health agency aims to reduce death and disability from snakebite envenoming by half over the next 12 years.

It kills, it heals

There is, however, more to snake venom than meets the eye.

Although life-threatening, it is also life-giving.

The only effective way to prevent or reverse a snakebite’s venomous effects is to develop a treatment from the venom itself.

In fact, snake antivenom is included in the WHO Essential Medicines List and should be available at the primary care level in areas where snakebites commonly occur.

But beyond developing anti-venom, Monash University Malaysia School of Sciences senior lecturer Dr Michelle Yap Khai Khun believes that there is more untapped potential in venom toxins.

“As deadly and dangerous as venom is, there are many areas to be explored in terms of its value.

“Besides killing prey, venom holds medical benefits.

“So there is interest in it for drug discovery,” says the scientist whose current research focuses on venom toxins’ pharmacology and future biotherapeutics.

Biotherapeutics refers to treatments produced by or involving living cells instead of drugs made from chemicals synthesised in the laboratory.

Dr Yap’s research focuses on the cytotoxins in the venom of the Equatorial spitting cobra or Sumatran cobra, which WHO classifies as a Category 1 venomous snake.

This category indicates that this snake species is of the highest priority for antivenom production, she explains.

Meanwhile, cytotoxins are substances that result in cell damage or cell death.

“Cobra envenomation appears to be one of the most common causes of envenomation, with high rates of illness and death.

“It is clinically manifested with systemic paralysis of the nerves and muscles, failure to breath, and local dermonecrosis (skin tissue death).

“The key venom toxin associated with dermonecrosis is due to substantial levels of cytotoxin in cobra venom,” she explains.

Through her research, Dr Yap hopes to better understand how these cytotoxins work and are processed by the body, in order to see how they might be utilised for other medical purposes, e.g. as anti-cancer agents.

She says: “Research has shown that when cancer cells are exposed to cytotoxins, they die.

“Now that we know they can kill cancer cells, we would like to know how this molecular target – the point at which toxins encounter the cells – can be used in drug delivery work.

“We want to know how we can encapsulate the toxic agent into nanoparticles and deliver them to targeted cancer cells.”

Stopping skin destruction

Antivenom is on the WHO Essential Medicines List and should be available in areas where poisonous snakes normally reside, like here at Universiti Kebangsaan Malaysia Medical Centre.Antivenom is on the WHO Essential Medicines List and should be available in areas where poisonous snakes normally reside, like here at Universiti Kebangsaan Malaysia Medical Centre.

Dr Yap also hopes to find a different antidote to dermonecrosis – the death or destruction of skin tissue – around the site of a snakebite.

This occurs due to certain components in the snake venom that destroy the tissues and cause the surrounding cells to die.

“Current treatment for envenomation involves doctors administering antivenom that is derived from the antibodies produced by horses.

“Antivenom of this origin needs to be injected into the bloodstream for it to be effective.

“But in cases of dermonecrosis, the venom is on the skin’s surface.

“Current antivenom is ineffective in stopping dermonecrosis, and that is one of its drawbacks,” she explains.

Antivenom is normally produced by injecting the venom in small and non-lethal, but sufficient, amounts to produce an immune response, into domestic animals.

The animals’ blood are then collected and the antibodies that specifically target the venom are purified from the blood serum.

Horses are commonly used because of their large size (allowing sufficient volume of blood to be collected without killing them), versatility (able to adapt well to various environments and climates), and ability to handle repeated administration of venoms.

“Ultimately, there needs to be antivenom that can be applied on the skin to treat dermonecrosis,” says Dr Yap.

Currently, snakebite victims with dermonecrosis receive surgical intervention.

Post-bite treatments are often neglected because of how costly they are to treat, causing victims to suffer from physical side effects and psychological problems.

The global shortage of cytotoxin-targeted biotherapeutics is due to a lack of knowledge in the area, she says.

“Many studies are conducted on how cytotoxins kill cancer cells, but I want to understand how they kill human skin cells.

“As there are so many different species of snakes, we are trying to combine the toxin sequences to reduce the discrepancy in our study to be more inclusive,” she says.

Snakes in town

People should take snakebite envenomation more seriously, as it is no longer a health issue that only concerns rural folks in Malaysia, Dr Yap says.

Urbanisation has resulted in snakes encroaching human habitats in the towns and cities.

Cobras and kraits are now commonly found in urban areas, in addition to their usual habitats of farms, swamps, fields and jungles.

More people are also keeping snakes as pets.

“If a snake owner gets bitten by a South American species, there would be no antivenom available to treat him,” she says.

Typically, countries only stock up on the antivenom of local species in the area.

There are more than 140 species of land snakes found in Malaysia.

According to the Health Ministry’s Guideline to Management of Snakebites, only about 17 of these are poisonous.

While there is greater access to health facilities in urban areas, antivenom is not as widely available as one would expect, according to Dr Yap.

“They are not cheap. Therefore, they can be found at selected government hospitals only,” she says.

Another point to note is that antivenom produced in animals may trigger allergic reactions in humans as the antibodies are foreign to the human body.

The worst-case scenario in such a situation would be sepsis, where an infection triggers a chain reaction throughout the body that can potentially lead to tissue damage, organ failure and death.

While Dr Yap notes that European researchers have started to use human antibodies in research on antivenom, she says: “If we can produce non-antibody-derived antivenom, it would be more affordable as we can upscale production and bring down the cost.

“As it involves small molecules, it would also be more efficient in drug delivery and can be produced in a laboratory.”

Funding continues to be the greatest challenge to such research, however, exacerbated by the pandemic.

“People have more interest in Covid-19 or other non-communicable diseases now.

“Snakebite really is a neglected tropical disease.

“But I’m glad that there is growing interest from some international funders like the Welcome Trust, the Royal Society of Tropical Medicine and Hygiene, and the Hamish Ogston Foundation to support research in this area.” she says.

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