It is small, 0.6 mm to 2 cm in size, but can cause considerable damage. Each year, the brown spider (Loxosceles sp) weighs about 7,000 people in Brazil – 7,441 in 2016, latest data available from the Sinan Information System of the Ministry of Health.
According to the researcher Denise Tambourgi, the ointment is made from tetracycline, a known substance and already used as an antibiotic.
Its venom can cause skin necrosis, kidney failure and even the death of victims – six years old that year.
To reduce these problems, scientists from the Butantan Institute (IB) have developed an ointment whose curative effects have already been demonstrated in tests on cell cultures and animals.
According to the IB researcher, Denise Tambourgi, main responsible for the work, the developed ointment is based on tetracycline, a substance known and already used as an antibiotic. "However, we used a lower concentration than would be microbicidal," he says.
"That is, lower than that required to be considered an antibiotic, but we use it at a dose capable of interfering with the activity of sphingomyelinase D, which is the main component of spider venom and participates in the inflammatory process and destruction of tissue (necrosis) and other effects. "
In addition to a skin lesion – which occurs in 80% of cases and may take months to heal – the bite of Loxosceles can also cause systemic effects in 20% of other victims, such as haemolysis (alteration, dissolution or destruction). red blood cells), platelet aggregation (which causes clots to form in the blood vessels that make circulation difficult or impede circulation), inflammation and kidney failure that can lead to death.
Origin of ointment
The history of Denise's research that led to the creation of ointment is long. She began to decipher the main components of the brown spider toxin in 1994. To do this, she and her team relied on genetic engineering.
As each Loxosceles produces very little venom – about 30 micrograms – it would be very difficult to get the amount needed for the studies. The researchers then inserted a gene from it into the Escherichia coli bacterium, creating a bioproduction of sphingomyelinase D, and produced it in a volume sufficient for research.
During the course of the work, Denise and her team discovered that brown spider venom can cause, in addition to known effects, secondary reactions, triggered primarily by the sphingomyelinase D protein.
"I often say that the poison gives only the" beginning "and that the protein modifies the cells," he explains.
Photo: Rafael Marques Porto / BBC News Brazil
"Then, there is a deregulation of the body, which leads to the production of proteases – enzymes whose function is to break the chemical bonds of Other proteins, which in turn causes cell death and necrosis, should be inhibited by the ointment ".
In summary, the study coordinated by Denise has deciphered the mechanism of venom action triggered by the brown spider as well as the cutaneous and systemic form of the disease.
Antidote test on the skin
The first tests, carried out on culture of human cutaneous cells, more specifically keratinocytes and fibroblasts, and on animals began to be carried out in 2005 and were prolonged until August 2018.
"We have experienced a lot by applying brown spider venom to crops," explains Denise. "As expected, the cells died, then we exposed them to toxin and tetracycline at multiple doses at the same time, and realized that the venom was no longer able to kill the cells. "
The researchers then went on to the next stage of the work, namely the animal test. "The rabbits were chosen because they are a good model for the study of cutaneous necrosis caused by Loxosceles toxin," says Denise. "The wound of this animal is similar to that which is formed in the man." We inject the poison into the skin and after a few hours, we start treating them with an ointment containing tetracycline and lanolin. take the medicine in the deep layers of the skin. "
The results were encouraging. In rabbits treated with tetracycline, the lesion quickly regressed. "The ointment has reduced the size of the lesion by about 80%," says Denise. "In the face of these findings, we have undertaken clinical trials in humans."
In rabbits treated with tetracycline, the lesion caused by brown spider venom quickly declined
Since tetracycline is a drug already tested for several infections and therefore used commercially, it is not necessary to go through the different test phases required by the research protocols for release. medication. It can be tested directly on the human. "In fact, we are only giving a new application to this substance," says the researcher.
This phase began in October. A total of 240 patients will be treated, including 120 with an ointment and 120 with a placebo, in 61 hospitals in Santa Catarina, the state in which occur the highest number of bites and in which Denise has several partnerships, including including the Federal University of UFSC, as well as doctors, nurses and professionals from the pharmacy and health sector. To date, 20 patients are already treated.
Those who receive a placebo will not stay untreated. They will receive what is used today for the bite, namely the specific antivenomous serum of the brown spider or a nonspecific, anti-arachnid toxin in general. The bites can also be treated with medications called corticosteroids, better known as corticosteroids.
If the results of the clinical trials are as expected, the ointment can reach the pharmacies. But there is no time limit for that. Once approved during testing, it still has to be published for use in humans and marketed by the National Health Surveillance Agency (Anvisa). If and when this happens, your market could be bigger than Brazil's.
In addition to accidents with Loxosceles in South America, Central America and North America, cases of bites have also occurred in Europe in recent years. Cases have been reported in countries such as Spain, France, Portugal and Italy. the death.
BBC News Brazil – All rights reserved. Unauthorized reproduction of BBC News Brazil is prohibited.
