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Epilepsy: the impulse goes in FM with a new type of drug

What do frog toxins to poison arrows, puffer fish, certain spiders and scorpions have in common with epilepsy drugs? The answer is that they all influence the ability of the nerves to transmit electrical impulses, affecting the ion channels in the nerves. The ion channels are small openings in the cellular membrane of the nerves that open and close as doors, in order to allow the electrically charged ions to enter or exit. When enough ions have flowed into the nerve cell, an electrical impulse is released and transmitted along the nerve. Sometimes, however, it becomes all too easy to release an electrical impulse. Increased electrical excitability of the nerves lies behind conditions such as seizures, heart rhythm and pain disorders. The anti-epileptic drugs currently in use and the above-mentioned animal toxins reduce the electrical excitability by closing a certain type of ion channel. All these previously known molecules bind to positions on the ion channel itself. These binding sites are generally surrounded by water. In contrast, the cell membrane crossed by the ion channel is constructed from a double layer of lipids that repels the water-soluble substances.

Researchers at Linköping University in Sweden have discovered a previously unknown molecular binding site that can influence electrical impulses in the nerves. The results are presented in the journal Science Advances. The discovery opens up the possibility of designing new types of drugs against conditions such as epilepsy. “We show that a small molecule is incorporated into the lipid double layer and has direct contact with the ion channel, which is a fundamentally different type of binding site.An interesting question is whether we have molecules present in the body that naturally bind to ionic channels. in the same way, we probably do it, “says Fredrik Elinder, a professor in the Department of Clinical and Experimental Medicine. Researchers who have conducted the study have previously discovered that naturally occurring resinic acids can regulate an ion channel that allows potassium ions to pass. The resin acids are found in coniferous resin, such as Swedish pine. Starting from one of the resinous acids, the chemists Xiongyu Wu and Peter Konradsson at the Department of Physics, Chemistry and Biology of LiU have created about 200 new molecules.

All new molecules are based on the same basic skeleton, with very small differences between them. Some of them influence the dependence on the ion channel tension and we believe that it will be possible to exploit this mechanism in future drugs. Researchers investigated the effect of substances on a channel of potassium ions from fruit flies. This ion channel is essentially the same in fruit flies and in humans. When the researchers wanted to examine in detail how the substances affect the ion channel, they discovered the new binding site. They also identified a strong relationship between the chemical structure of substances and their effect on the ion channel. “Now that we have found this site binding, it is possible that we or other scientists can identify additional molecules that bind to it. Our results provide information on how we can modify substances to make them as effective as possible,” says Fredrik Elinder. About one-third of people with epilepsy still experience seizures even during treatment, and currently available anti-epileptic drugs often have side effects such as fatigue and dizziness. The researchers hope that drug-like substances can be developed into new drugs against epilepsy.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Pubblicazioni scientifiche

Ottosson NE et al., Elinder F. Sci Adv. 2017; 3(10):e1701099.

Liin SI et al., Elinder F. Acta Physiol (Oxf). 2016; 218(1):28-37. 

Ottosson NE et al., Elinder F. Sci Rep. 2015 Aug 24; 5:13278.

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it

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