Destigmatisation of epilepsy in children through education-rehabilitation camps

Edukacijsko – rehabilitacijski kampovi za djecu i adolescente oboljele od epilepsije organiziraju se širom svijeta i pokazali su se izuzetno korisnima kako za djecu samu, tako i za obitelj, kao i za njihovo školovanje i osamostaljenje (Cvitanović Šojat 2010). U Hrvatskoj je epilepsija kao kronična bolest velika nepoznanica za djecu koja boluju od te bolesti i njihove roditelje. Isto tako izražena je nedovoljna informiranost o postojanju edukacijsko rehabilitacijskih kampova za djecu s epilepsijom. Cilj ovog istraživanja je ispitati razlike u znanju o epilepsiji djece polaznika edukacijsko rehabilitacijskih kampova i kako boravak u kampu doprinosi samostalnosti polaznika u daljnjem svakodnevnom životu s epilepsijom. U istraživanju su sudjelovala djeca i adolescenti s epilepsijom, polaznici Kampa 2011 i djeca i adolescenti s epilepsijom polaznici Kampa 2013. Sva navedena djeca kontroliraju svoju bolest u Klinikama za pedijatriju KBC Zagreb, KBC Sestre milosrdnice, Klinika za dječje bolesti Zagreb i u Poliklinici Sabol, a svi su članovi Hrvatske udruge za epilepsiju (HUE). U istraživanju je sudjelovalo ukupno 33 djece, 2011. godine njih 20-tero, a 2013. godine njih 18-tero, međutim je 5-tero djece sudjelovalo u oba kampa. Obradom podataka utvrđeno je da je došlo do povećanja znanja o epilepsiji nakon kampa u skupini 2011.g. (t= -3,835; p<0,01), skupini 2013.g. (t= -7,721; p<0,01) te u obje skupine zajedno (t= - 6,981; p<0,01). Za nas je bilo osobito važno saznati da postoji stigma kod oboljelih od epilepsije s obzirom na tajenje podataka o dijagnozi od nastavnika (42% razrednik nije upoznat sa dijagnozom), od ostalih učenika (45% ne zna da im školski kolega ima epilepsiju), a neki nisu obavijestili o svojoj bolesti bilo koga u školi. Prema odgovorima u upitnku o prilagodbi na život s epilepsijom također se vidi da je jako izražena stigma u oboljele djece s epilepsijom. Ovim radom prvi put je opširno prikazano postojanje edukacijsko rehabilitacijskih kampova za djecu s epilepsijom u Hrvatskoj, a dobivenim rezultatima u istraživanju prikazana je neophodna potreba za organizacijom istih u svrhu destigmatizacije što se potvrđuje i podacima iz svjetske literature.Educational-rehabilitation camps for children and adolescents with epilepsy are organized throughout the world and have been shown very helpful for children and their families as well as for their education and independence (Cvitanović-Šojat 2010). In Croatia epilepsy as chronic disease is a big unknown for children with the disease and their parents. Insufficient information is available on existence of educational-rehabilitation camps for children with epilepsy. Aim of this study is to evaluate differences in knowledge on epilepsy among children attending the camp and to evaluate how attending the camp enhances independence of children with epilepsy in their everyday life. The study included children and adolescents with epilepsy who attended the Camp 2011 and Camp 2013. All the children were patients in Pediatric clinic KBC Zagreb, KBC Sestre milosrdnice, Clinic for children’s diseases Zagreb and in Sabol Polyclinic, and they were all members of Croatian epilepsy association. There were total of 33 children included in the study. 2011 there were 20 children and 2013 there were 18 children, among which five attended both camps. Statistical analysis showed there was increased knowledge on epilepsy after the camp in group from year 2011. (t= -3,835; p<0,01), in group from year 2013. (t= -7,721; p<0,01) and in both groups together (t= - 6,981; p<0,01). For us it was very important to find out there is still stigma with epilepsy as they were hiding the disease from the teachers (in 42% main teacher didn’t know the diagnosis), hiding from other students (45% didn’t know their peer had epilepsy), and some didn’t let anyone in school know about their disease. According to answers in the questionnaire on living with epilepsy there is very high stigma in children with epilepsy. This study is the first one to extensively show existence of educational-rehabilitation camps for children with epilepsy in Croatia, and the results obtained show the need for continuation of the camps in order to destigmatize epilepsy, and this is shown in world literature as well

Destigmatisation of epilepsy in children through education-rehabilitation camps

Edukacijsko – rehabilitacijski kampovi za djecu i adolescente oboljele od epilepsije organiziraju se širom svijeta i pokazali su se izuzetno korisnima kako za djecu samu, tako i za obitelj, kao i za njihovo školovanje i osamostaljenje (Cvitanović Šojat 2010). U Hrvatskoj je epilepsija kao kronična bolest velika nepoznanica za djecu koja boluju od te bolesti i njihove roditelje. Isto tako izražena je nedovoljna informiranost o postojanju edukacijsko rehabilitacijskih kampova za djecu s epilepsijom. Cilj ovog istraživanja je ispitati razlike u znanju o epilepsiji djece polaznika edukacijsko rehabilitacijskih kampova i kako boravak u kampu doprinosi samostalnosti polaznika u daljnjem svakodnevnom životu s epilepsijom. U istraživanju su sudjelovala djeca i adolescenti s epilepsijom, polaznici Kampa 2011 i djeca i adolescenti s epilepsijom polaznici Kampa 2013. Sva navedena djeca kontroliraju svoju bolest u Klinikama za pedijatriju KBC Zagreb, KBC Sestre milosrdnice, Klinika za dječje bolesti Zagreb i u Poliklinici Sabol, a svi su članovi Hrvatske udruge za epilepsiju (HUE). U istraživanju je sudjelovalo ukupno 33 djece, 2011. godine njih 20-tero, a 2013. godine njih 18-tero, međutim je 5-tero djece sudjelovalo u oba kampa. Obradom podataka utvrđeno je da je došlo do povećanja znanja o epilepsiji nakon kampa u skupini 2011.g. (t= -3,835; p<0,01), skupini 2013.g. (t= -7,721; p<0,01) te u obje skupine zajedno (t= - 6,981; p<0,01). Za nas je bilo osobito važno saznati da postoji stigma kod oboljelih od epilepsije s obzirom na tajenje podataka o dijagnozi od nastavnika (42% razrednik nije upoznat sa dijagnozom), od ostalih učenika (45% ne zna da im školski kolega ima epilepsiju), a neki nisu obavijestili o svojoj bolesti bilo koga u školi. Prema odgovorima u upitnku o prilagodbi na život s epilepsijom također se vidi da je jako izražena stigma u oboljele djece s epilepsijom. Ovim radom prvi put je opširno prikazano postojanje edukacijsko rehabilitacijskih kampova za djecu s epilepsijom u Hrvatskoj, a dobivenim rezultatima u istraživanju prikazana je neophodna potreba za organizacijom istih u svrhu destigmatizacije što se potvrđuje i podacima iz svjetske literature.Educational-rehabilitation camps for children and adolescents with epilepsy are organized throughout the world and have been shown very helpful for children and their families as well as for their education and independence (Cvitanović-Šojat 2010). In Croatia epilepsy as chronic disease is a big unknown for children with the disease and their parents. Insufficient information is available on existence of educational-rehabilitation camps for children with epilepsy. Aim of this study is to evaluate differences in knowledge on epilepsy among children attending the camp and to evaluate how attending the camp enhances independence of children with epilepsy in their everyday life. The study included children and adolescents with epilepsy who attended the Camp 2011 and Camp 2013. All the children were patients in Pediatric clinic KBC Zagreb, KBC Sestre milosrdnice, Clinic for children’s diseases Zagreb and in Sabol Polyclinic, and they were all members of Croatian epilepsy association. There were total of 33 children included in the study. 2011 there were 20 children and 2013 there were 18 children, among which five attended both camps. Statistical analysis showed there was increased knowledge on epilepsy after the camp in group from year 2011. (t= -3,835; p<0,01), in group from year 2013. (t= -7,721; p<0,01) and in both groups together (t= - 6,981; p<0,01). For us it was very important to find out there is still stigma with epilepsy as they were hiding the disease from the teachers (in 42% main teacher didn’t know the diagnosis), hiding from other students (45% didn’t know their peer had epilepsy), and some didn’t let anyone in school know about their disease. According to answers in the questionnaire on living with epilepsy there is very high stigma in children with epilepsy. This study is the first one to extensively show existence of educational-rehabilitation camps for children with epilepsy in Croatia, and the results obtained show the need for continuation of the camps in order to destigmatize epilepsy, and this is shown in world literature as well

Niemann-Pickova bolest tip C: mutacije gena NPC1 i tijek bolesti

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder caused by mutations in the NPC1 gene in 95% of cases. Consequently, unesterifi ed cholesterol accumulates in late endosomes/lysosomes causing extremely varied neurovisceral symptoms. For many countries including Croatia, there are no reported NP-C cases to date, mainly because the accurate diagnosis of NP-C requires not easily accessible biochemical and molecular-genetic laboratory tests. Therefore, with the aim to improve clinical practice and understanding of NP-C in the region, we present the fi rst siblings with NP-C recorded in Croatia. The diagnosis was based on histologic, biochemical and genetic tests. Namely, fi lipin staining showed accumulation of unesterifi ed cholesterol and cultured skin fi broblasts were defi cient in esterifi cation of exogenously administered cholesterol. Electron microscopy of skin biopsy revealed the presence of sequestrated lipids in lysosomes. Molecular analyses showed both siblings to be compound heterozygotes for two disease-causing mutations of NPC1 protein, N1156S and Q922X. Based on comparison with previously reported N1156S homozygotes, we propose that Q922X mutation, causing the formation of a truncated NPC1, has a more severe impact on clinical outcome. Further, we observed pronounced diff erences in the disease course in the siblings; i.e. in the boy we observed an earlier onset and a much faster neurologic deterioration (late infantile onset), suggesting other genetic and/or environmental factors infl uencing the course of the disease. In contrast, the girl exhibited juvenile type of NP-C. In conclusion, when progressive neurologic symptoms develop in late childhood and with a previous history of neonatal cholestasis, the classic late infantile or juvenile type of NP-C must be suspected.Niemann-Pickova bolest tip C rijedak je autosomni recesivni poremećaj, u 95% slučajeva uzrokovan mutacijama gena NPC1. Kao posljedica mutacija dolazi do nakupljanja neesterifi ciranog kolesterola u kasnim endosomima/lizosomima, što uzrokuje vrlo raznolike neurovisceralne simptome. U mnogim zemljama, uključujući Hrvatsku, do danas nema opisanih slučajeva ove bolesti, uglavnom zbog toga što su za postavljanje točne dijagnoze potrebne teško dostupne biokemijske i molekularno-biološke laboratorijske pretrage. Stoga radi poboljšanja kliničke prakse i razumijevanja ove bolesti u regiji, opisujemo prvi slučaj brata i sestre oboljelih od NP-C-a za Hrvatsku. Dijagnoza se temeljila na histološkim, biokemijskim i genetičkim pretragama. Nakupljanje neesterifi ciranog kolesterola dokazano je „Filipin” bojenjem, a nedostatna esterifi kacija izvana unijetog kolesterola dokazana je u kulturi fi broblasta. Elektronskom mikroskopijom biopsije kože dokazane su nakupine lipida u lizosomima. Molekularna analiza je pokazala da su brat i sestra heterozigoti, nositelji dviju mutacija gena NPC1, te je predviđeno da proteini NPC1 nose mutacije N1156S i Q922X. Temeljem usporedbe s podatcima iz literature o N1156S homozigotima, pretpostavljeno je da je mutacija Q922X, koja uzrokuje preuranjeni završetak translacije proteina NPC1, značajnije utječu na kliničku sliku. Uz to su razlike u tijeku bolesti kod dječaka i djevojčice bile vrlo izražene. Kod dječaka su se prvi simptomi pojavili mnogo ranije i došlo je do bržeg neurološkog propadanja (kasni infantilni tip bolesti), vjerojatno zbog utjecaja drugih genetskih i/ili okolišnih čimbenika na tijek bolesti. Nasuprot tome, djevojčica je imala juvenilni tip bolesti. Zaključno, ako se nakon zabilježene neonatalne kolestaze u kasnom djetinjstvu pojave progresivni neurološki simptomi, treba posumnjati na klasični kasni infantilni ili juvenilni tip NP-C-a

Destigmatisation of epilepsy in children through education-rehabilitation camps

Edukacijsko – rehabilitacijski kampovi za djecu i adolescente oboljele od epilepsije organiziraju se širom svijeta i pokazali su se izuzetno korisnima kako za djecu samu, tako i za obitelj, kao i za njihovo školovanje i osamostaljenje (Cvitanović Šojat 2010). U Hrvatskoj je epilepsija kao kronična bolest velika nepoznanica za djecu koja boluju od te bolesti i njihove roditelje. Isto tako izražena je nedovoljna informiranost o postojanju edukacijsko rehabilitacijskih kampova za djecu s epilepsijom. Cilj ovog istraživanja je ispitati razlike u znanju o epilepsiji djece polaznika edukacijsko rehabilitacijskih kampova i kako boravak u kampu doprinosi samostalnosti polaznika u daljnjem svakodnevnom životu s epilepsijom. U istraživanju su sudjelovala djeca i adolescenti s epilepsijom, polaznici Kampa 2011 i djeca i adolescenti s epilepsijom polaznici Kampa 2013. Sva navedena djeca kontroliraju svoju bolest u Klinikama za pedijatriju KBC Zagreb, KBC Sestre milosrdnice, Klinika za dječje bolesti Zagreb i u Poliklinici Sabol, a svi su članovi Hrvatske udruge za epilepsiju (HUE). U istraživanju je sudjelovalo ukupno 33 djece, 2011. godine njih 20-tero, a 2013. godine njih 18-tero, međutim je 5-tero djece sudjelovalo u oba kampa. Obradom podataka utvrđeno je da je došlo do povećanja znanja o epilepsiji nakon kampa u skupini 2011.g. (t= -3,835; p<0,01), skupini 2013.g. (t= -7,721; p<0,01) te u obje skupine zajedno (t= - 6,981; p<0,01). Za nas je bilo osobito važno saznati da postoji stigma kod oboljelih od epilepsije s obzirom na tajenje podataka o dijagnozi od nastavnika (42% razrednik nije upoznat sa dijagnozom), od ostalih učenika (45% ne zna da im školski kolega ima epilepsiju), a neki nisu obavijestili o svojoj bolesti bilo koga u školi. Prema odgovorima u upitnku o prilagodbi na život s epilepsijom također se vidi da je jako izražena stigma u oboljele djece s epilepsijom. Ovim radom prvi put je opširno prikazano postojanje edukacijsko rehabilitacijskih kampova za djecu s epilepsijom u Hrvatskoj, a dobivenim rezultatima u istraživanju prikazana je neophodna potreba za organizacijom istih u svrhu destigmatizacije što se potvrđuje i podacima iz svjetske literature.Educational-rehabilitation camps for children and adolescents with epilepsy are organized throughout the world and have been shown very helpful for children and their families as well as for their education and independence (Cvitanović-Šojat 2010). In Croatia epilepsy as chronic disease is a big unknown for children with the disease and their parents. Insufficient information is available on existence of educational-rehabilitation camps for children with epilepsy. Aim of this study is to evaluate differences in knowledge on epilepsy among children attending the camp and to evaluate how attending the camp enhances independence of children with epilepsy in their everyday life. The study included children and adolescents with epilepsy who attended the Camp 2011 and Camp 2013. All the children were patients in Pediatric clinic KBC Zagreb, KBC Sestre milosrdnice, Clinic for children’s diseases Zagreb and in Sabol Polyclinic, and they were all members of Croatian epilepsy association. There were total of 33 children included in the study. 2011 there were 20 children and 2013 there were 18 children, among which five attended both camps. Statistical analysis showed there was increased knowledge on epilepsy after the camp in group from year 2011. (t= -3,835; p<0,01), in group from year 2013. (t= -7,721; p<0,01) and in both groups together (t= - 6,981; p<0,01). For us it was very important to find out there is still stigma with epilepsy as they were hiding the disease from the teachers (in 42% main teacher didn’t know the diagnosis), hiding from other students (45% didn’t know their peer had epilepsy), and some didn’t let anyone in school know about their disease. According to answers in the questionnaire on living with epilepsy there is very high stigma in children with epilepsy. This study is the first one to extensively show existence of educational-rehabilitation camps for children with epilepsy in Croatia, and the results obtained show the need for continuation of the camps in order to destigmatize epilepsy, and this is shown in world literature as well

Utility of camp for children with epilepsy: a retrospective

Cilj: Cilj ovog istraživanja bio je procijeniti dobrobiti obrazovnih i rekreacijskih programa kampiranja za djecu s epilepsijom. Metoda: Proveden je retrospektivni pregled podataka prikupljenih od sve djece koja su pohađala godišnje kampove za epilepsiju u organizaciji Hrvatske udruge za epilepsiju i Gradskog ureda za zdravstvo Grada Zagreba tijekom 8 godina. Uključena su djeca u dobi od 6 do 18 godina. Osoblje kampa uključuje dječje neurologe, psihologe, neurološke medicinske sestre i educirane volontere. Edukativne aktivnosti osmišljene su kako bi poboljšale znanje djece o epilepsiji, važnosti uzimanja lijekova, akademskim izborima, predloženom zaposlenju i propisima koji se odnose na zakone o vožnji. O tim pitanjima raspravljalo se u skupinama ili u pojedinačnim sesijama, ovisno o slučaju. Ostale aktivnosti uključivale su plivanje pod nadzorom, timske sportove, zabavne aktivnosti i igre, umjetnost i rukotvorine te zabavu poput diska ili filmske večeri. Svaki od sudionika ispunio je tri upitnika 1. Upitnik s općim podacima i provjeru znanja prije kampa; 2. Upitnik o zadovoljstvu kampom i provjera znanja nakon kampa; 3. Upitnik o prilagodbi na epilepsiju u mladih. Rezultati: Analize anketa i testova pokazuju da je samo 75% djece u kampu znalo da boluje od epilepsije. U 10% djece prijatelji i dalji članovi obitelji nisu znali za epilepsiju. Uspoređujući provjeru znanja prije i nakon kampa, prosječan postotak točno riješenih zadataka na prvom testu je 65%, a na drugom 87%. Odgovori u upitniku o prilagodbi na život s epilepsijom pokazatelji su jake stigme kod djece s epilepsijom. Zaključci: Glavno postignuće kampa bilo je da djeca steknu samopouzdanje da mogu ostvariti svoj puni potencijal u životu i da se osjećaju ravnopravno sa svojim vršnjacima u svakom aspektu života.Objective: The aim of this study was to evaluate the benefits of educational and recreational camping programs for children with epilepsy. Method: A retrospective review of data collected from all children attending annual epilepsy camps organized by the Croatian Epilepsy Association and the Zagreb City Office for Health during 8 years was performed. Children included were between 6 and 18 years of age. The staff of the camp includes child neurologists, a psychologist, neurology nurses and trained volunteers. Educational activities are designed to improve children’s knowledge of epilepsy, importance of taking medication, academic choices, suggested employment, and regulations regarding driving laws. These issues were discussed in groups or in single sessions, depending on the case. Other activities included supervised swimming, team sports, fun activities and games, arts and crafts and entertainment such as disco or movie night. Each of the participants filled out three questionnaires 1. General data questionnaire and pre-camp knowledge test; 2. Camp satisfaction questionnaire and post-camp knowledge test; 3. Questionnaire on adaptation to epilepsy in young people. Results: The analyses of surveys and tests showed that only 75% of children in camp knew that they had epilepsy. In 10% of children, friends and distant family members did not know about epilepsy. Comparing the knowledge test before and after the camp, the average percentage of correctly solved tasks on the first test is 65%, and on the second 87%. The answers in the questionnaire on adaptation to life with epilepsy are indicators of strong stigma in children with epilepsy. Conclusions: The main accomplishment of the camp was for children to gain confidence that they can reach their full potential in life and to feel equal to their peers in every aspect of life

Genska terapija v onkologiji, prvi razvojni koraki v Sloveniji

Gene therapy is also attracting interest in oncology. Probably the most interesting approach is immunostimulation. Plasmid DNA can be constructed, which is coding for a specific immunostimulatory molecule, which is then delivered into the cells, either in tumour or normal tissue. The transfected tissue then becomes the producer of the molecules encoded in the plasmid. The product is then released from the cells, either locally or systemically into the bloodstream. Since plasmids have hampered transport through the plasma membrane, delivery systems are needed that are either viral or nonviral. In our studies we predominantly use the non-viral transfection system, based on electroporation of the cells.Interleukin 12 (IL-12) is a cytokine with well-known anti-tumour and anti-angiogenic function. Therefore, in the SmartGene.si project we wanted to construct a plasmid DNA which is coding for IL-12 (plasmid phIL12), and perform all the necessary testing and prepare the documentation for its clinical testing in the treatment of skin tumours. The SmartGene.si consortium comprises partners from academia and industry. In the project it was necessary to prepare the plasmid according to the European Medicinal Agency (EMA) recommendations. For the application for the study approval submitted to the Agency for Medical Products and Medical Devices of the Republic of Slovenia (JAZMP), it was necessary to perform pharmacological, pharmacokinetic, and efficiency testing of phIL12. Thereafter, we had to develop the process and the facility, and prepare the drug.During the last three years, we have achieved all the goals and obtained the approval of the JAZMP for clinical testing of the product phIL12 in humans. We also obtained the approval of the National Ethics Committee. Currently, we are testing phIL-12 in a Phase I clinical protocol on head and neck skin tumours, with the aim to test the safety and feasibility of intratumoral gene electrotransfer of the plasmid phIL12. Another goal of the study is to determine a suitable dose of plasmid that could be used in future studies as adjuvant treatment to ablative therapies such as radiotherapy or electrochemotherapy.Genska terapija postaja čedalje bolj zanimiva tudi v onkologiji. Med aplikacijami je morda najzanimivejša imunostimulacija. Pripravimo lahko plazmidno DNA, ki nosi zapis za različne imunostimulatorne molekule, ki jih vnesemo v celice tumorjev ali normalnih tkiv. Ta tkiva postanejo proizvajalci teh molekul, ki lahko delujejo lokalno ali pa se izločajo tudi sistemsko v krvni obtok. Ker plazmidna DNA ne prehaja celične membrane, so potrebni dostavni sistemi, virusni ali nevirusni. V naših študijah uporabljamo predvsem nevirusni dostavni sistem – elektroporacijo.Interlevkin 12 (IL-12) je eden od zanimivih citokinov, za katerega je znano protitumorsko delovanje s spodbujanjem imunskega odziva in antiangiogenim delovanjem. Namen projekta SmartGene.si je bil pripraviti plazmid z zapisom za interlevkin 12 (plazmid phIL12) in pripraviti vse potrebno za njegovo klinično testiranje za zdravljenje kožnih tumorjev. V konzorciju smo združili moči s partnerji z akademskega in industrijskega področja. Treba je bilo pripraviti plazmid za uporabo v humani onkologiji po zahtevah Evropske agencije za zdravila (EMA). Za prijavo klinične študije na Javno agencijo za zdravila in medicinske pripomočke (JAZMP) smo morali izvesti tudi vse neklinične raziskave o varnosti in učinkovitosti zdravila. Nato je bilo treba razviti postopek priprave zdravila, zagotoviti primerne prostore za pripravo in izvedbo postopka priprave zdravila.V treh letih smo dosegli vse te zastavljene cilje in dobili dovoljenje za izvajanje klinične študije na kožnih tumorjih, ki ga je izdala JAZMP na osnovi pozitivnega mnenja Komisije Republike Slovenije za medicinsko etiko. Zdaj poteka klinična študija faze I preizkušanja plazmida phIL12 na kožnih tumorjih glave in vratu z namenom preveriti varnost in sprejemljivost genskega elektroprenosa plazmida v tumorje. Cilj študije je prav tako določiti primeren odmerek zdravila, ki bi ga v nadaljnji klinični študiji uporabili kot adjuvantno zdravljenje k ablativnim terapijam, kot sta radioterapija ali elektrokemoterapija

Gene therapy in oncology, first steps of development in Slovenia

Genska terapija postaja čedalje bolj zanimiva tudi v onkologiji. Med aplikacijami je morda najzanimivejša imunostimulacija. Pripravimo lahko plazmidno DNA, ki nosi zapis za različne imunostimulatorne molekule, ki jih vnesemo v celice tumorjev ali normalnih tkiv. Ta tkiva postanejo proizvajalci teh molekul, ki lahko delujejo lokalno ali pa se izločajo tudi sistemsko v krvni obtok. Ker plazmidna DNA ne prehaja celične membrane, so potrebni dostavni sistemi, virusni ali nevirusni. V naših študijah uporabljamo predvsem nevirusni dostavni sistem – elektroporacijo. Interlevkin 12 (IL-12) je eden od zanimivih citokinov, za katerega je znano protitumorsko delovanje s spodbujanjem imunskega odziva in antiangiogenim delovanjem. Namen projekta SmartGene.si je bil pripraviti plazmid z zapisom za interlevkin 12 (plazmid phIL12) in pripraviti vse potrebno za njegovo klinično testiranje za zdravljenje kožnih tumorjev. V konzorciju smo združili moči s partnerji z akademskega in industrijskega področja. Treba je bilo pripraviti plazmid za uporabo v humani onkologiji po zahtevah Evropske agencije za zdravila (EMA). Za prijavo klinične študije na Javno agencijo za zdravila in medicinske pripomočke (JAZMP) smo morali izvesti tudi vse neklinične raziskave o varnosti in učinkovitosti zdravila. Nato je bilo treba razviti postopek priprave zdravila, zagotoviti primerne prostore za pripravo in izvedbo postopka priprave zdravila. V treh letih smo dosegli vse te zastavljene cilje in dobili dovoljenje za izvajanje klinične študije na kožnih tumorjih, ki ga je izdala JAZMP na osnovi pozitivnega mnenja Komisije Republike Slovenije za medicinsko etiko. Zdaj poteka klinična študija faze I preizkušanja plazmida phIL12 na kožnih tumorjih glave in vratu z namenom preveriti varnost in sprejemljivost genskega elektroprenosa plazmida v tumorje. Cilj študije je prav tako določiti primeren odmerek zdravila, ki bi ga v nadaljnji klinični študiji uporabili kot adjuvantno zdravljenje k ablativnim terapijam, kot sta radioterapija ali elektrokemoterapija.Gene therapy is also attracting interest in oncology. Probably the most interesting approach is immunostimulation. Plasmid DNA can be constructed, which is coding for a specific immunostimulatory molecule, which is then delivered into the cells, either in tumour or normal tissue. The transfected tissue then becomes the producer of the molecules encoded in the plasmid. The product is then released from the cells, either locally or systemically into the bloodstream. Since plasmids have hampered transport through the plasma membrane, delivery systems are needed that are either viral or nonviral. In our studies we predominantly use the non-viral transfection system, based on electroporation of the cells. Interleukin 12 (IL-12) is a cytokine with well-known anti-tumour and anti-angiogenic function. Therefore, in the SmartGene.si project we wanted to construct a plasmid DNA which is coding for IL-12 (plasmid phIL12), and perform all the necessary testing and prepare the documentation for its clinical testing in the treatment of skin tumours. The SmartGene.si consortium comprises partners from academia and industry. In the project it was necessary to prepare the plasmid according to the European Medicinal Agency (EMA) recommendations. For the application for the study approval submitted to the Agency for Medical Products and Medical Devices of the Republic of Slovenia (JAZMP), it was necessary to perform pharmacological, pharmacokinetic, and efficiency testing of phIL12. Thereafter, we had to develop the process and the facility, and prepare the drug. During the last three years, we have achieved all the goals and obtained the approval of the JAZMP for clinical testing of the product phIL12 in humans. We also obtained the approval of the National Ethics Committee. Currently, we are testing phIL-12 in a Phase I clinical protocol on head and neck skin tumours, with the aim to test the safety and feasibility of intratumoral gene electrotransfer of the plasmid phIL12. Another goal of the study is to determine a suitable dose of plasmid that could be used in future studies as adjuvant treatment to ablative therapies such as radiotherapy or electrochemotherapy