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A blow to post-trauma epilepsy

A Unifesp project has resulted in a patent request for medicine based on scopolamine salts, substances normally used to treat amnesia, which can avoid the appearance of the illness in victims who have received substantial head injuries

The first drug with the potential to avoid the emergence of post-trauma epilepsy, a consequence of the illness arising from a strong blow to the head, is coming to life from the study conducted by the team of Dr. Luiz Eugênio Araújo de Moraes Mello, of the Neurophysiological Laboratory of the Federal University of São Paulo (Unifesp). In laboratory tests, the administration of scopolamine salts, a medicine originally used to provoke amnesia, is capable of avoiding the appearance of this form of epilepsy in 15% of the rodents that had suffered serious trauma to the head.

The results were exciting even among the rodents that weren’t cured. In those animals the convulsive crises were took three times longer to occur or appeared with less frequency and in an isolated form, a pattern totally different from that exhibited by the rodents not submitted to the treatment, who kept on having constant and successive crises on the same day. “It is important to point out that in human beings, similar injuries to those simulated in the animals lead to a situation of epilepsy in 50% of the cases and not in 100% as occurred with the guinea pigs”, explains Mello, whose research project received close to R$ 400,000.00 from FAPESP and also counted upon the participation of the scholarship students Cristina Massant and Simone Benassi. “In this way, if we were able to extrapolate the results with the animals to those of humans, the index of success of scopolamine could reach 30%.”

At the maximum of one year, the results of the experiments with the salts of scopolamine in monkeys will be concluded and tests on humans should begin.Confident in his discovery and cautious against eventual copies, the researcherhas already registered the patent of the new medicine in Brazil and in more than 30 other countries. For this expense he received R$ 7,800.00 from the Patenting and Licensing of Technology Center (Nuplitec) of FAPESP. Annually, the market for drugs against epilepsy grosses around US$ 2 billion only in the United States, Japan and Europe. Since it is a medicine with a specific potential use, scopolamine could cut reap a small fraction of this total.

The drugs available today on the market are efficient only in the control of convulsion crises in 80% of patients. For the remaining 20% the only possible solution in some cases is surgery with the removal of the portion of the damaged brain as the solution to the condition. “Until now, there is no medicine capable of preventing the crises of post-trauma epilepsy.” stated Mello. In theory, the possible consumers for the new drug under development are 9 million people on the planet. The doctors estimate that close to 1% of the worldpopulation (60 million individuals) suffer from some type of epilepsy. In close to 85% of the cases, the illness develops from genetic factors or from the existence of a tumor or a head surgery. In 15% of the patients the infirmity originates from head traumas.

Only these patients, and not the complete total of sufferers, are candidates for the use of scopolamine salts. In the Mello’s view, between 15% and 50% of the victims of serious head traumas develop epilepsy after some time. The appearance of the problem depends on the area and the extension of the injury. “The risk of epilepsy in people with head trauma is 13 times higher than in the population in general.” affirms the doctor. In the United States, 400,000 people suffer head injuries per year and 5% of them, or 20,000 individuals, develop a situation of post-trauma epilepsy. In Brazil, there are no statistics available on the number of people who suffer head traumas and end up becoming victims of the illness. During the research with rodents, the administration of scopolamine salts injections got started three hours after the occurrence of the trauma and was extended for two weeks. The good results of the treatment led the Unifesp doctors to believe that this situation was sufficient to prevent the appearance of epilepsy in a good number of head injury victims.

The scopolamine action
Scopolamine is a substance that reacts on the sensitive receptors of acetylcholine, a neurotransmitter that makes the connection between the neurons. These receptors divide themselves into two types, those sensitive to nicotine and those to muscarine. Scopolamine reacts mainly on the second group, which are called muscarinic receptors, which exist in abundance in the nervous system. When it acts on these receptors, the scopolamine causes temporary amnesia in the individual. The idea behind the use of the substance is to avoid post-trauma epilepsy exactly by provoking a loss of memory in the brain. “We believe that the amnesia is a condition necessary to block the development of epilepsy.” says the researcher.

Mello explains this concept, which has similar logic to the induced coma, which lowers the brain activity in order to minimize injuries in this organ: “I believe that on certain occasions, epilepsy is a learning process. In these cases, after having suffered an acute injury, the brain launches emergency mechanisms in order to recover, making the remaining neurons re-organize themselves so that they can again carry out their functions. However, this re-organization is not always perfect and the brain, on many occasions, gets damages such as epilepsy. This occurs when the re-organization of the neurons is done in a quick and disorganized manner. With scopolamine, we are attempting to carry out this re-ordering in a slow and gradual manner and consequently much more successfully.”

Besides being used to cause a loss of memory in human beings, scopolamine, when associated with another derivative, named butyl, is used in the treatment ofspasms. In this case the derived substance is butyl-scopolamine, which is the main active ingredient of Buscopan, a medicine made by the German laboratory Boehringer Mainheim, developed during the decade of the 60’s.

The good research results with the salts of scopolamine have attracted the attention of the pharmaceutical industry. “We are in negotiations with the laboratory Novartis, which makes medicines for the treatment of epilepsy. Our intention is that the company take over the human clinical tests on humans. After all, they have more know-how to do this.” says Mello. Should the negotiations be successful, any resulting dividends will be split among the researchers, FAPESP and Unifesp. The doctor’s expectation is that, if all runs well, the medicine could be sold in less than five years.

The project
Use of Scopolamine Salts in the Prevention of Post Trauma Epilepsy (99/11387-4); Modality: Assistance to research project; Coordinator: Dr. Luiz Eugênio Araújo de Moraes Mello – Unifesp; Investment: US$ 158,876.00 and R$ 114,770.29