Ďakujem za spoluprácu a inšpiráciu!

Rozhodla som sa ukončiť moju prácu externého spolupracovníka pre MZ SR a venovať sa už len  biznisovým a dobrovoľníckym aktivitám. Piatok 11.9.2020 bol môj posledný pracovný deň. Po vyše 3,5 rokoch spolupráce v rámci Inštitútu výskumu a vývoja sa nám s tímom podarilo mnoho užitočných vecí pre biomedicínsku komunitu, mnoho vecí sa naštartovalo a niektoré budú ešte len dobiehať.

Z profesného priestoru určite neodchádzam a budem sa naďalej venovať vyhľadávaniu a hodnoteniu zaujímavých biomedicínskych a biotechnologických myšlienok a projektov, pomoci pripravenosti tímov na komercializáciu, kompetetívnej analýze, hľadaniu možností financovania pre ne, príprave a zlepšovaniu projektov, vedeckému a inovačnému copywriting-u, vzdelávaniu a iným aktivitám. Som otvorená aj novým možnostiam. Je možné aj to, že opäť opustím na čas tento geografický priestor.

Pri svojej práci pre MZ SR som stretla veľa zaujímavých a aktívnych ľudí, ktorým záležalo na tom, aby sa Slovensko aj v biomedicínskej oblasti pohlo dopredu. Želám im, aby im štát venoval v budúcnosti toľko pozornosti, koľko si zaslúžia. Ide o naše zdravie a životy.

Ďakujem vám všetkým za spoluprácu, inšpiráciu a motiváciu!

Aké testy na koronu vlastne existujú?

V posledných týždňoch sme sa všetci dozvedeli viac ako sme kedy chceli vedieť o vírusoch, antimikrobiálnych prostriedkoch a procedúrach, ktoré sa skôr používajú vo vedeckých laboratóriach pri práci s bunkovými kultúrami a mikroorganizmami. Sledujeme, koľko diagnostických testov a aké k nám prichádzajú, diskutujeme, či je počet testov dostatočný a polemizujeme o tom, koľko stáli a koľko mohli stáť. Poďme sa teraz pozrieť na to, aké druhy testov sa na SARS-CoV-2 používajú. Úplne na začiatok si musíme povedať 4 dôležité veci:

  1. Každý diagnostický test, ktorý sa má použiť v Európskej únii, musí mať známku CE, ktorá (momentálne do určitej miery) zaručuje, že zloženie testu, jeho technické prevedenie a hlavne klinické použitie zabezpečí, že test „funguje“. Test musí mať klinicky stanovené, aká je jeho špecificita a senzitivita, čiže koľko určí falošne pozitívnych a koľko prípadov nezachytí vôbec, dôležitý pri pandémii je hlavne ten druhý prípad. Okrem toho, musí mať test stanovenú aj technickú citlivosť a špecificitu, t.j aké sú krajné hodnoty, ktoré je možné technicky s testom zachytiť.  Okrajovo poznamenávam, že pravdepodobne nijaký test na 100% nezaručí, že zachytí všetky prípady alebo že všetky pozitívne prípady sú naozaj pozitívne. Nové EU pravidlá na diagnostické testy, ktoré vstúpia do platnosti v máji 2022, budú oveľa prísnejšie ako tie dnešné a bude náročnejšie ich splniť.
  2. Nemocnice, respektíve zdravotnícke zariadenia si môžu diagnostický test pripraviť aj sami, a to hlavne vtedy, ak komerčný CE test nie je k dispozícii. Môžu ním testovať len pacientov vo vlastnom zariadení. Tieto testy však tiež musia spĺňať určité nevyhnutné podmienky a musia sa porovnávať s pozitívnymi či negatívnymi kontrolami.
  3. Ak má krajina na to vedecký a klinický potenciál, mala by zapracovať na tom, aby testovanie vlastného obyvateľstva robila vo vlastnej réžii, s použitím bežne dostupných chemikálií a prostriedkov a s testom/testami, ktoré majú šancu získať CE značku. Dôležité je, aby testy boli prispôsobené realite krajiny, dostupnému prístrojovému vybaveniu a ľudským zdrojom pre odber vzoriek a testovanie. Vo svetle informácií o budúcich vlnách a nových vírusových infekciach by bolo asi najvhodnejšie mať vyvinutú platformu, v ktorej by sa špecifické súčasti dali jednoducho vymeniť, validovať a použiť na nové testovanie nového vírusu či mutantu „starého“ vírusu.
  4. Všetky uvedené druhy testov majú svoju hodnotu, len je ich treba použiť v správnom čase, zo správnych dôvodov a v správnej kombinácii.

V zásade máme tieto druhy diagnostických testov:

  1. Testy založené na kultivácii intaktných vírusov zo vzoriek z respiračného traktu, zo stolice a zriedkavo z moču či tkaniva sa pri bežnej diagnostike takmer vôbec nepoužívajú kvôli nebezpečnosti a zdĺhavosti. Tieto metódy sú však dôležité pri detekcii kmeňa vírusu, ktorý koluje v populácii a pri zisťovaní celkovej sekvencie vírusu a stanovení rýchlosti či rozsahu mutácií pôvodného kmeňa. Tieto informácie sú dôležité pre poznanie „nepriateľa“.
  2. Testy založené na detekcii nukleovej kyseliny SARS-CoV-2, v prípade tohto konkrétneho vírusu sa jedná o RNA vírus. To znamená, že obsahuje RNA molekuly a popri tom aj proteíny a sacharidy, ktoré sa nazývajú glykány.

Tieto testy, ak sú nastavené správne, detekujú prítomnosť vírusu na určitom mieste v organizme v určitom čase- v prípade SARS-CoV-2 sa najčastejšie robia výtery z hrdla a nosa a zisťuje sa prítomnosť v týchto vzorkách. Podľa informácií z Číny, prítomnosť nukleových kyselín (v tomto prípade RNA) SARS-CoV-2 bola potvrdená v krvi u asi 40% pacientov a v stolici asi u 60% pacientov, ktorí mali vírus vo výteroch z hrdla a nosa.

Testy na stanovenie RNA vírusu sa najčastejšie robia pomocou metódy RT-PCR, kde sa z vyizolovanej RNA syntetizuje DNA a pomocou špecifických primerov sa stanoví, či sa vo vzorke nachádza daný vírus. Tieto testy sa považujú za najcitlivejšie a najhodnovernejšie, bežne však trvá dlhšie sa dopracovať k výsledku.

Pred pár dňami však bol napríklad v USA schválený test firmy Abott, ktorý využíva ich platformu ID NOW™ a stanoví SARS-CoV-2 vo vzorkách pomocou „namnoženia“ (amplifikácie) nukleových kyselín do 30 minút. Takýto test sa dá použiť priamo v ambulancii, prípadne v nemocnici na rýchle stanovenie SARS-CoV-2. Vyžaduje však špecifické malé prenosné zariadenie a špecifické chemikálie. Test v jednom momente môže však analyzovať len jednu vzorku, čo nie je veľmi použiteľné na skríning pacientov.

Silnou stránkou testov založených na RNA/DNA je vysoká citlivosť (aj keď je potrebné klinickú a technickú citlivosť stanoviť pri každom takomto teste) a možnosť automatizácie. Slabou stránkou testov môže byť napríklad sústredenie sa na nevhodné/nešpecifické častí vírusu, čím sa neodlíšia podobné vírusy. Správnym nastavením testu sa tieto nedostatky dajú odstrániť.

  1. Testy založené na stanovení vírusových antigénov, čo znamená priamu detekciu proteínových častí prítomného vírusu. Vírusové antigény sú vlastne tie molekuly, proti ktorým vie telo zamerať špecifickú imunologickú obranu a neskôr aj vytvoriť protilátky, keď sa vírus dostane do organizmu. Výhodou týchto testov je ich rýchlosť, môžu byť vyhodnotené okamžite (z vhodnej vzorky, najčastejšie z hrdla a nosa, prípadne zo stolice a dokonca aj z krvi) a môžu byť dostupné aj ako domáce testy. Nevýhodou je, že pri tejto metóde sa testovaná látka „nenamnoží“ tak ako pri teste RT-PCR a preto má test obyčajne nižšiu citlivosť. Nižšia citlivosť znamená, že test na SARS-CoV-2 bude pozitívny až pri určitom počte vírusových častíc prítomných vo vzorke. Ďaľšou nevýhodou je, že je potrebné v laboratóriu vytvoriť špecifické činidlá (protilátky), pomocou ktorých sa vírusové proteíny budú stanovovať.
  2. Testy založené na imunitnej odpovedi organizmu na prebiehajúcu infekciu, ide o stanovenie protilátok v krvi pacientov. Každá infekcia vyvoláva imunitnú reakciu organizmu, v prípade nového mikroorganizmu telo musí nanovo vytvoriť na daný patogén odpoveď. V rámci imunitnej odpovede telo aktivuje špecifické nástroje a to hlavne bunkovú imunitnú odpoveď, T-lymfocyty a protilátkovú imunitnú odpoveď, tvorbu špecifických protilátok. Okrem toho je aktivovaná aj vrodená imunita a množstvo nešpecifických molekúl je uvoľnených do krvi v snahe zvládnuť boj proti patogénu.

Na tvorbe protilátok je založená aj aktívna imunizácia alebo očkovanie, kde sa vytvárajú podmienky na tvorbu protilátok, schopných zasiahnúť proti mikroorganizmu. Tvorba protilátok je v neskoršej fáze nahradená prítomnosťou buniek, ktoré sú schopné protilátky okamžite produkovať, keď sa telo opäť stretne s tým istým patogénom.

Stanovenie protilátok v krvi má nesmierny význam a to hlavne z 3 hlavných dôvodov:

  1. Prítomnosť špecifických protilátok je dôkazom toho, že telo sa s infekciou nedávno stretlo a daný pacient je do určitej miery a do určitého času (v prípade SARS-CoV-2 zatiaľ nevieme túto mieru a čas) odolný voči ďalšej infekcii tým istým mikroorganizmom a mohol by sa zapojiť do bežného života, napríklad do zdravotnej starostlivosti bez nebezpečenstva ďalšej nákazy.
  2. Jedinci s vysokou koncentráciou neutralizačných alebo celkových protilátok môžu byť zdrojom lieku pre najťažšie prípady. Neutralizačné protilátky sú napríklad také, ktoré zabraňujú vírusu preniknúť do bunky a atakovať orgány, napr. pľúca.
  3. Celoplošné testovanie populácie na prítomnosť protilátok môže spätne pomôcť zistiť, aký bol rozsah epidémie na danom území, čo môže byť dôležité pre stanovenie úmrtnosti a pre sledovanie účinnosti opatrení, pre zistenie správania sa vírusu a pre budúce modelovanie.

Okrem stanovenia neutralizačných protilátok v teste priamo s vírusom sa môžu použiť aj kvantitatívne metódy, ktoré pri správnom dizajne a nastavení nepotrebujú pracovať priamo s vírusmi. Stanovenie protilátok z krvi sa robí pomocou testov EIA, respektíve ELISA. V zásade musíme mať pre test v skúmavke k dispozícii antigén, t.j. proteínovú časť vírusu, ktorá je schopná vyvolať v ľudskom tele tvorbu protilátok. Tento antigén sa môže vyrobiť aj synteticky alebo biotechnologicky a je to úplne neinfekčný materiál.

Ak by sme vzali do úvahy predchádzajúcu epidémiu SARS-CoV v roku 2003, tak protilátky IgM aj IgG sa v krvi detekovali už 7.deň po infekcii vírusom. Protilátky IgM sa z krvi vytrácali po približne 2-3 mesiacoch, čiže predstavovali viac akútnu časť infekcie, respektíve skorú post-akútnu fázu. IgG pretrvali v krvi približne 12 mesiacov. Podobné poznatky zatiaľ nie sú veľmi dostupné pre SARS-CoV-2, aj z toho dôvodu, že sa všetci sústreďujú logicky na skoré a spoľahlivé zistenie prítomnosti vírusu viac ako na stanovenie protilátok.

Pre zaujímavosť prikladám článok, ktorý síce ešte nebol recenzovaný, ale ponúka pohľad a návod na zostavenie protilátkového testu.

  1. Iná diagnostika– napríklad digitálna diagnostika. Už dnes sú validované a vo vývoji metódy, ktoré diagnostikujú COVID19 ako ochorenie spôsobené vírusom SARS-CoV-2 pomocou charakteristického obrazu CT pľúc. Pre účely Slovenska nie je táto diagnostika relevantná, lebo CT sa nepoužíva v takej miere. Môže sa však aplikovať na iné, bežnejšie zobrazovanie a to RTG. Iné experimentálne metódy sa zameriavajú na stanovenie tzv. prchavých organických látok v dychu pacienta. Výskumníci tiež testujú elektrické stanovenie nukleoproteínu vírusu SARS-CoV-2 pomocou nanosenzorov a aptamérov.

Z existencie veľkého množstva už certifikovaných testov či testov vo vývoji je zrejmé, že záujem firiem či inštitúcií je veľký. Najväčší počet testov má z pochopiteľných dôvodov Čína. Pekný prehľad je možné nájsť napríklad na tejto stránke. 

Krajina by si mala sama určiť, ako bude postupovať pri získavaní a zavádzaní relevantných testov. Do úvahy je treba brať aj nasledovné faktory:

  • Dostupnosť odborných pracovníkov na analýzy
  • Dostupnosť odberových tímov a mobilných jednotiek
  • Dostupnosť zariadení na testovanie
  • Dostupnosť základných chemikálií
  • Informácie o kmeni /kmeňoch vírusu na svojom území
  • Dostupnosť relevantného know-how v tej-ktorej krajine a možnosť vytvorenia vlastného CE testu

V každom prípade by však mala byť zabezpečená jednotná platforma, kde by sa zhromažďovali relevantné informácie a ukladali dáta. Krajina by si mala zabezpečiť zhromažďovanie vzoriek od svojej populácie, aby mohla získať dôležité vedecké poznatky pre zvládnutie ďalších vĺn epidémie na svojom území ako aj v európskom či svetovom priestore. Mala by sa vytvoriť biobanka obyvateľstva, v ktorej by sa zhromaždili údaje o chorých, ich testoch a ďalších parametroch a ich biologické vzorky. Vytvorenie takejto databanky by malo začať u potvrdených chorých a malo by pokračovať naprieč obyvateľstvom.

Pre vytvorenie a fungovanie biobanky je potrebná podpora štátu a súčinnosť relevantných stakeholderov. Biobanka by samozrejme mohla a mala byť využívaná aj na iné ochorenia ako koronavírus. V biomedicínskom svete tvorí národná biobanka a jej prepojenie na iné národné biobanky nevyhnutnú súčasť výskumu a vývoja- či už nových liekov, diagnostiky, zdravotníckych pomôcok či postupov a prevencie.

Výzva pre SK “stakeholderov” v oblasti HEALTH!

Slovenskí stakeholderi v oblasti HEALTH, ak chcete, aby aj vaše záujmy boli vyjadrené v novonavrhovanom európskom PP partnerstve nazvanom Innovative Health Initiative (IHI), zapojte sa do prieskumu do 10.1.2020!

IHI je PP partnerstvo v rámci pripravovaného Horizon Europe a je nadstavbou predchádzajúcich programov IMI a IMI2, kde spolu s Európskou komisiou (EC) financovali inovatívne HEALTH projekty aj farmaceutické firmy. Teraz je možnosť zapojiť aj iných stakeholderov HEALTH oblasti- malé i väčšie biotech a medtech firmy, poskytovateľov zdravotnej starostlivosti, zdravotné poisťovne, pacientske organizácie a, samozrejme farmaceutické firmy a akademické tímy.

Slovensko nebolo v IMI2 (roky 2014-2020) zapojené ani do jedného, jediného projektu, čo je veľká škoda, lebo to boli (a stále sú) projekty s hodnotnými výstupmi a zaujímavou finančnou podporou.

Ak chceme, aby malo Slovensko možnosť sa do iniciatívy IHI v novom programovom období zapojiť, musíme vyjadriť svoj názor a svoje predstavy. EC sa pýta aj Slovenska, aký má názor na pripravovaný koncept a čo sú slovenské priority v oblasti HEALTH.  Preto by ste si mali nájsť čas zapojiť sa do prieskumu, ktorý nájdete na tejto linke.

Pre správne zapojenie sa je potrebné si prečítať aj vysvetľujúci dokument, ktorý je uvedený v prieskume.

Ďakujeme za váš hlas v prieskume, odmenou bude možnosť zapojenia sa slovenských tímov do IHI projektov v oblastiach a témach relevantných pre Slovensko.

Slovak life science innovations

Are we ready to sustain innovations in Slovak healthcare? Do we support sufficiently biomedical, drug, diagnostics and medical devices research and development in Slovakia? What does it mean for the patient´s prognosis and treatment modalities when circulating tumour cells are found in blood? Can we diagnose prostate cancer earlier and more accurate without a need for non-necessary biopsies? Can encapsulated islets into polymers effectively treat diabetes? Why we urgently need a biobank system in Slovakia? How are Slovak researchers contributing to the development of a drug for alkaptonuria? How can a new antibacterial material which needs just light to kill bacteria be useful in hospitals?

These and many other emerging questions and answers were discussed on the 2. Life Science Innovation Day in Bratislava in the Science Park of Comenius University. The event attracted more than 125 stakeholders of life science innovations in Slovakia. It was a great opportunity to meet also Boehringer Ingelheim researchers to hear about how innovation meets accountability or to discuss with Siemens Healthineers about the future of healthcare with personalised and value-based medicine.

Thanks to Slovensko-nemecká obchodná a priemyselná komora (Deutsch-Slowakische Industrie- und Handelskammer) and Ministerstvo zdravotníctva SR (Ministry of Health of SR) we could meet Slovak life science innovators and see that this sector is alive and active in Slovakia.

See you there next year?

Biosamples storage without refrigeration; Central Europe attractive for vaccine manufacturers; Zika virus for brain tumors treatment; Mechanism of lactoferrin antitumor features

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

  • What if we do not need to store biological samples in refrigerator before analysis ? This would allow to send samples for special analyses to labs even from remoted areas and people could get more adequate diagnosis and subsequently also treatment even in areas without electricity, refrigerators and freezers.
  •  Are Central European countries attractive for vaccine manufacturers? According to the latest news on new or expanded factories, yes. It is only a pity that Slovakia has not yet attracted any such vaccine manufacturer or developer- this can be interesting among other reasons also due to presence of highly qualified people in life sciences in the country and also due to latest rules regarding tax deductions of expenses for R&D and a new “patent box” law affecting positively tax height from patented product sales.
  •  Hard to believe but Zika virus can be in future used to fight brain tumors. It might be that the Zika virus research will instruct people how to defeat the most aggressive tumor types- tumors of CNS.
  •  Slovak and Austrian scientists explain why lactoferrin posses its anticancer features. This protein from human milk inhibits spreading of cancer cells.

 

No need for refrigerating of biological samples- just place it on a filter paper

All people working in the biological field are aware of importance of refrigeration of biological samples as plasma, urine, blood, etc. Rapid destruction of proteins, nucleic acids and metabolites observed at room temperature lead to incorrect and misleading results, sometime even impossibility to analyze a sample. What if there is a technology which can preserve important molecules like proteins in samples in such way that they can be just placed on a filter paper and sent to a laboratory for analysis?

 Researchers at Washington University are developing a method which can remove a need for a cold chain in processing of biosamples. If proven as reliable and robust, it can not only decrease expenses of analyses but it can also contribute to improved access to such analyses of people in remote geographical areas. A notable effect is also a better standardization of the biosamples storage and thus improvement of reliability of subsequent analyses. Researchers “used a nanoporous material to essentially shrink wrap protein biomarkers in blood and urine samples by growing crystals around the molecules. Then, they transferred the shrink-wrapped molecules onto standard lab filter paper. Once dry, the paper can be shipped at any temperature to a lab for testing.”

Central Europe is involved in expansion plans of vaccine companies: A new vaccine plant in Czech Republic and an expanded Hungarian vaccine facility

Through the deal to buy Nanotherapeutics in the Czech Republic (72 mil EU deal), Serum Institute of India will get a former Baxter flu vaccine factory in the Czech Republic. This plant has an ambition to become the largest injectable polio vaccine factory by capacity in the coming years. The investment to get the plant up and running is planned up to 40 mil EUR. Injectable inactivated polio vaccines are according to WHO recommended to be used for vaccination against polio.

GSK is expanding with its vaccines sales and it needs to expand also manufacturing of the vaccines and its components. The Hungarian factory in Gödöllö will be enlarged by the 40 mil GBP investment. The production of diphtheria toxoid and tetanus toxoid will be moved from GSK’s Marburg production site in Germany.

Zika virus can be in future used to fight brain tumors

It is hard to believe that it can be something good on Zika virus in humans. Zika virus infect predominantly neural stem cells and is therefore more harmful to developing fetus than to adult humans. Scientists in Brazil wanted to figure out whether the virus also attack tumor stem cells in the central nervous system (CNS). And they succeeded. By focusing on embryonal CNS tumors, which are very aggressive and which are manifesting shortly after birth or up to adolescence, they showed on tumor cell lines and in cells-induced mice tumors that small amounts of Zika virus is able to infect these cells and in parallel, destroy cells and the cell-induced tumors. The mechanism behind cells and tumors destruction is apparently oncolysis.

In addition, human adult neural cells were neither infected by Zika virus not destroyed at the dose used. Research also suggest that other tumors of CNS like glioblastoma can be also feasible targets for Zika virus-related destruction.

There are of course still more questions than answers but what if such kind of approach can work? This is not of course a first example of an oncolytic virus use for cancer treatment (see e.g the very recent up to $1 Billion deal of Janssen). It might be that the Zika virus research will instruct people how to fight one of the most aggressive tumor types- tumors of CNS.

Protein from human milk inhibits cancer

Plasminogen system belongs to important systems in human organism, above all it removes protein aggregates, especially fibrin clots. If it does not work properly, one can get thrombosis and this can be a life-threatening state. On the other side, as many other molecules in human body, plasminogen is involved in different pathological processes, just to name tumor cells dissemination, neurodegeneration and various inflammatory disorders. Slovak and Austrian scientists found that the human glycoprotein from human milk- lactoferrin- can inhibit plasminogen activation by direct binding to it. Lactoferrin was able to inhibit tumor cells invasion. In addition to that, lactoferrin also inhibited plasminogen activation by a microorganism species Borellia.

Dr. Vladimir Leksa, the scientist at the Molecular Immunology Unit of HAI, CePII, MUW, Vienna, Austria and at the Slovak Academy of Sciences (SAS), Bratislava, Slovakia: “Lactoferrin is a long time known as an immunomodulatory molecule with antimicrobial and antitumor activities. Thus, to use lactoferrin for treatment is not a new concept. It is a milk protein, which makes it biologically safe for such type of studies. Its function as a plasminogen activation inhibitor revealed by us was so far not known and may explain many of its biological activities. According to our data, it targets cell-associated plasminogen activation resulting in inhibition of cell migration, including tumor cell and bacteria invasion. We are planning further mouse experiments to support and explore further the findings”.

Slovakia 2017 and the Velvet Revolution 1989

One non-scientific article about my country, our journey since 1989 and our success.

Twenty eight years ago our country woke up. We, students went into streets in Czechoslovakia and our parents could not believe that this time freedom was coming. They had their experiences from 1968, time when many of us, their children, were still not even born. In 1968, small Czechoslovakia was attacked by „friendly armies“ from all directions and nobody cared. Again.

aktuality.sk

aktuality.sk

But 1989 was different. However, we did not know at beginning where it will be ending up. We were risking our life, health, freedom, carreer. We were instructed what to do if we were arrested. Our parents were afraid. But we were just young and fresh. And we wanted better future. Future where there will be more than just two TV programmes, future where we can travel and meet people in other countries, shops where we can buy oranges not just at Christmas time…

nezna revolucia_srdce

Slovak and Czech people raised their heads, hands and voices. Hands with keys which rang the grave to communism and occupation. And the world belonged to us, students. We were discussing, arguing, convincing, creating, breaking down. With naivity and innocence of young people. But it was a great experience to build and live a revolution! And it stays in many of us still…

Source: Aktuality.sk

Source: Aktuality.sk

When I have a look back on these 28 years, our country has changed a lot since that time. We have our own state, we are belonging to the developed world and we have managed to grow with an enormous rate. And our sons and daughters, who are already working, are becoming a new and fresh generation who will soon direct where Slovakia is going. We, former students of the Velvet revolution ´89, can just say that freedom did not come automatically and it was not for free.

Today, Slovakia, as a sovereign state and a valid member of the European Union and NATO, is growing and progressing continuously. And it is doing a good job.

Slovakia is Peter Sagan, one of the best cyclists in the world. Petra Vlhova and Veronika Zuzulova, excellent skiers. Marek Hamsik, a professional footballer, serving as the captain for the Italian club Napoli.

Slovakia means also beautiful mountains, lakes, natural springs and spa, places for holidays, leisure, sport.

Slovakia is the first in the world in car production per capita, with factories of Volkswagen, Kia, Peugeot-Citroen and in building Jaguar Land Rover.

Slovakia is Amazon with its biggest reverse logistic center and the corporate office. Slovakia is Dell and IBM.

Slovakia is Eset, the Slovak IT security firm with branches in 180 countries of the world.

Slovakia is also Highchem s.r.o, a biotech company which with its technology and database is helping pharmaceutical companies, intelligence services, mobile and IoT providers and many others.

Slovakia is Jan Vilcek, a professor, born in Bratislava, living and working in USA, co-inventor of Remicade.

Slovak people are behind Sli.do and Staffino.com. Slovak people are in Google, Microsoft, Apple, Amazon, Facebook. And about 30 Slovak people are working as EMA staff.

Slovakia is also the demining set Bozena, which is preventing thousands of deaths by removing mines in mining fields.

I apologize for all those I have not mentioned. It would be a long list of Slovak successes and successful Slovak people. We are happy that many people are already returning home from abroad after they obtained valuable experiences and skills. They are bringing a fresh air and new work and living styles.

We are not only demanding, we are also offering. We are not only listening, we are speaking. We are not only using, we are creating. We are not only awaiting, we are active. We are not only complaining, we are solving. Slovakia has changed a lot since November 1989. We are free.

And you know what? Even if the European Medicine Agency will not be moved to Slovakia, we will continue with our progress. Despite many historical disfavours, we are going forward with heads up and we are proud on our country, Slovakia.

Picture made by using wordclouds.com

Why I like this nonmedical “therapy” for dementia?

Knowing “disease-causing genes” is not enough, we need to take in account also many if not all other genes; Glycans as (not only) cancer biomarkers; Why I like these nonmedical therapies for dementia

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.
My MedScan in the past weeks.

We are in the middle of summer, thought weather does not fit to that at all and I am still in front of my holidays 🙂 My son has successfully graduated from university with excellent evaluation, I am so proud on him! And I have collected “tons” of peaches from my garden and gave away many of them to my neighbours…

Knowing “disease-causing genes” is not enough, we need to take in account also many if not all other genes
A usual view on how the genes affect development of diseases might be changed soon. Stanford researchers in their new paper showed that not only disease-modifying genes focused around certain disease pathways but virtually any gene in the individual´s gene pool adds to the heritability of a disease. These thousands of genes with their small but altogether significant adding up to the “core” gene set might explain why some people do not get a certain disease despite a clear predisposition found in gene analysis and vice versa.

As Stanford researchers say: “…we propose that disease risk is largely driven by genes with no relevance to disease and is propagated through regulatory networks to a much smaller number of core genes with direct effect. If this model is correct, then it implies that detailed mapping of cell-specific regulatory networks will be essential task for fully understanding human disease biology”.

There are strong implications for basic science and therapeutic approaches, if the model which scientists call an “omnigenic” model, is correct. At the end, the message is quite clear- we need to look at what happens in our organism in much more complex way as we have looked until now. And this is true not only on a gene level.

Glycans as (not only) cancer biomarkers
Most of the intracellular as well as extracellular proteins are glycosylated. Glycosylated proteins, as recognised in the recent decade, are involved in processes of coding and decoding of biological information, in other words, they play important role in diseases and health. As the glycosylation pattern of a protein can be changed during development of a disease and treatment, simple, fast and cheap methods to assess these patterns are highly desired.

Czech and Slovak researchers have recently published a paper where they introduce a label- and reagent-free method for detection of interactions of sialylated protein PSA (prostate specific antigen, a biomarker for prostate cancer) with two important lectins based on an electrochemical principle. This electrochemical method can be used for distinguishing of healthy people and patients with prostate cancer and has many other uses as well.

Furthermore, the Slovak authors of this publication, the group of Dr. Jan Tkac, are very active in developing of different diagnostic approaches and devices based on glycans in area of oncological, metabolic and virus diseases. Worthy to check!

Why I like these nonmedical therapies for dementia?
After being confronted with many partial pieces over recent years on Alzheimer´s disease as one of the dementia diseases, I am very excited to see a more complex approach. This approach, without drawing a “warranted” hypothesis on dementia causes, is however nonmedical (actually not using a special drug for that purpose) and it collects published findings, experiences and observations throughout human life.

Imagine that one third of about 47 millions living with dementia today would never develop it. Subtract at least the same amount of caregivers and we are not talking yet about costs. And imagine that it could be in our hands, in the way how we live and how we take care of our health.

24 international experts involved in the Lancet Commission on Dementia Prevention and Care systematically reviewed existing research and came with evidence-based recommendations on prevention of dementia development. And their approximation on decreasing dementia cases is very promising- one third of all dementia cases can be prevented if we start already in early life. Recommendations are connected to education, life style, taking care of our health and social connections. But far more, the paper is very informative and instructive in individual as well as community approaches to tackle dementia and to provide all possible care to the affected people.

The one third decrease in dementia cases can be achieved by increasing early life education, addressing hearing loss, decreasing obesity and hypertension in middle life and stopping smoking, treating depression, increasing physical activity and social contacts and managing diabetes in late life. Nine main points which can be achieved by all of us if we care.

And why I like this approach so much? Firstly, we have it in our hands, it increases everybody´s own responsibility for her/his health. Secondly, apparently decreasing of dementia cases by one third as projected by the Commission would be so far the biggest success we have ever seen with any dementia treatment/prevention efforts. And, third, it is showing us clearly that living and interacting with other human beings is very useful for our health and being with our old loved ones, including them into our life, protecting them, activating them, helping and taking care can increase their chance to live without dementia. Might be we will need such caring as well, once. I would say, a highly recommended reading for everybody, from young people to governments, offered for free (against registration) by Lancet.

Picture made by using wordclouds.com

New biomarkers in AD; $300m for European biotechs; Multiple sclerosis detection; Artificial intelligence

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.
My MedScan in the past weeks.

It seems that my regular blog became irregular:-) Nevertheless, I am continuing exploring the biomedicine world and I will bring from time to time some interesting news and opinions.

Metabolomics for biomarker research in Alzheimer´s disease

Processes which lead to development of Alzheimer´s disease (AD) start according to some scientists already 20 years before the disease is clinically manifested. Treatment at time of confirmed AD seems to come too late to reverse damage already done and to stop further disease progress. We still do not know why somebody gets AD and somebody not. Drug development failures over the recent years in very late clinical stages can reflect the fact that we try to treat too late and/or we are focusing on consequences and not on triggering events. Biomarker research in AD is a drug development accompanying process and it seems that scientists have another piece to the whole puzzle.

Researchers from the Boston University School of Medicine assessed 217 circulating metabolites in more than 2000 dementia-free participants of the Framingham Offspring Cohort Study over many years. They identified four biologically plausible candidate plasma biomarkers for dementia. A significant association between higher plasma antranilic acid levels and increased risk of incident dementia was found. This acid is a part of the kynurenine pathway which is the main pathway for degradation of an essential amino acid tryptophan (precursor of serotonine). All in all, this analysis shows an importance of looking at more wide angles as we have done until now in AD.

$300m for late-stage innovative therapeutics development in European biotechs

Medicxi, a life sciences-focused investment firm, grown from the the Index Ventures and started operations in 2016, has got a huge financial injection, $300m from Google (via its Verily), Novartis and the European Investment Fund (shareholders of the EIF are the European Investment Bank, European Commission and public and private financial institutions and banks). Their Medicxi Growth 1 fund will help European biotechnology companies and institutions to develop therapeutical products from Phase II and further. This initiative is apparently focused on improvement of an access to financing of European health biotechnology sector, regardless of whether private or public. Situation in Europe is much worse than the situation in US in this area.

Medicxi also invests into early-stage companies and even starts and grows companies out of labs, academia or Pharma. Along with Novartis, another two world-class pharmaceutical companies, GSK and J&J, are also strategic partners of the company.

Diagnosing Multiple Sclerosis with a blood test?

Multiple sclerosis (MS) is an autoimmune disease, affecting more than 2,5 million people world-wide. Diagnosis of MS is usually confirmed after brain MRI, cerebrospinal fluid testing and several clinical criteria. There are however attempts to diagnose MS and other autoimmune diseases from blood.

IQuity is developing an RNA-based tests which are based on their technology licensed from the Vanderbilt University. The tests focus on determination of the molecular portrait of long non-coding RNAs (lncRNAs). As the company previously showed, one lncRNA was differentially expressed in rheumatoid arthritis patients and it responded to therapy. lncRNAs expression pattern is very specific for a particular type of a cell.

By using the Isolate MS kit, one can determine so far whether somebody has the disease or not. Further development and definition of clinical criteria are needed to be able to assess the progress of the disease by such tests.

Artificial intelligence for drug discovery and personalized research for ALS

I have observed the US company Insilico Medicine already for some time. They use artificial intelligence and deep learning for mining of knowledge about aging and other areas and apply this knowledge for biomarker research and drug development.

I like such systemic approach which does not focus just on one pathway or one target but take in account all available information about a disease published. E.g, with more than 27 million papers in PubMed, huge amount of knowledge is already out there.

Insilico Medicine has recently launched ALS.AI, a personalized drug discovery and biomarker platform for Amyotrophic Lateral Sclerosis, a deadly rare disease affecting nerves and muscles. “Insilico Medicine used its pathway activation analysis algorithms to identify the dysregulated pathways that were associated with the patient’s ALS disease….The collaborator is validating the newly identified treatments before they may be used to treat the patient (some of the medications were approved by FDA for the treatment of other diseases)”.

Created by using wordclouds.com

PD drugs lost in translation; FDA vs EMA; HD code and a “heavy” pill; Regeneron´s hypercholesterolemia drug 2

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw 5-14

After a non-voluntary break, here is again my MedScan. This time it is dedicated to a woman who is not anymore with us. Good night, Julia.

Here we go:

Parkinson´s disease drug candidates are good for mice but are they also good for humans?
Yale researchers have been curious why so many Parkinson´s disease drug candidates failed to translate promising results found in animal studies to humans. After evaluating more than 500 animal and human studies, they found that humans are not the same as mice. But, seriously, something is not correct with the design of the animal studies. Findings on either symptomatic or prospectively disease modifying candidates showed no real differences.

And what have been the most interesting findings? Using predominantly males, interventions given too early before or right at the onset of the PD in a model animal, less commonly measured clinical outcomes and single time point assessment of outcomes. In contrast, PD experimental treatment is given to humans with developed disease, both sexes are tested and appropriate clinical outcomes are measured at multiple time points. Time to find where we are lost in translation. And definitely not only in PD.

FDA approves drugs more quickly than EMA
Researchers studying approval times for drugs in US by FDA and in Europe by EMA (note: EMA is evaluating and recommending drugs for approval or refusal and it is the European Commission which is at the end approving marketing authorization in Europe) clearly showed that there are differences between them. FDA needed less time for approval in comparison to EMA evaluation and this gap is increasing in recent years. Also, FDA approved more drugs than its European counterpart.

As I showed in my report on authorized drugs in 2015 in Europe (free for download on my website), the situation is even more different in number of new drugs firstly approved in Europe. Most of the new drugs in EU had been approved firstly in USA- more than 77% and only after that they were approved in EU.

Some of the new drugs had been approved in USA years before EU, some only a few days. As I mentioned in my report, this could reflect preferences of companies applying for market authorisation, different lengths and requirements of authorisation process in USA and in EU, an attitude of authorisation agencies to certain treatments and potentially also differences of drug development activities in Europe and USA.

Cracking the code of Huntington’s disease?
Huntington’s disease is caused by a gene mutation that causes a protein to build up in the brain. In a world first, EPFL scientists have synthesized and studied modified forms of a mutant part of the protein, deepening our understanding of how it contributes to the disease, and pointing to new therapeutic strategies for treating it.

Despite of importance of a huntingtin gene mutation in development of Huntington’s disease, post-translational modifications of the huntingtin protein like phosphorylation and acetylation have their roles in onset and severity of the disease. EFPL scientists focused on the mutant huntingtin exon1 (Httex1) which “has been shown to be sufficient for reproducing key features of Huntington’s disease in animal models”.

Using chemical and bacterial synthesis of the mentioned Httex1, researchers paired modifications of the protein to structural changes and characteristics. They found a protective phosphorylation on position 3 (T3) which interferes with the huntingtin’s ability to aggregate, mimicking threonine with another similar amino acids did not fully reproduced these results. Finally, they also showed an impact of acetylation on  three lysin amino acids. One acetylation reversed a protective effect of the T3 phosphorylation. Next steps would be to find enzymes which are involved in these processes and eventually use them as targets for HD drug development.

A new drug for HD´s chorea approved by FDA- a first “heavy” pill
Teva can be satisfied, its Austedo has been approved by FDA for treatment of Huntington’s disease chorea and it is only the second FDA approved drug for HD. What is special on this drug is the fact that it is the first approved drug containing the “heavy” hydrogen, deuterium. This substitution of hydrogens in tetrabenazine showed slowing down of drug metabolism and thus decreasing amount of a drug needed for the same effect. Austedo was waiting for several months for approval since it showed “certain” metabolites found in patients. The drug was approved accompanied by warning on depression and suicidality. Another application for tardive dyskinesia is under Priority Review at FDA.

For those interested in deuterated drugs in general, here is the patent and development review from 2014. It is obvious that big pharma companies like Pfizer, Merck, GSK, Roche and others tested potential of such drugs. However, it was Auspex (acquired by Teva for 3,5 billions dollars 2 years ago) which had the most progressed clinical studies with its SD-809, now Austedo. The second in the row seem to be Concert Pharmaceuticals and Avanir with their deuterated dextromethorphan (AVP-786) in Phase III for Alzheimer’s agitation and in Phase II for other neurological conditions.

Regeneron and hypercholesterolemia- PCSK9 is not their only target
Very recently, the Regeneron´s evinacumab, received the FDA’s Breakthrough Therapy Designation status. Evinacumab is a monoclonal antibody to angiopoietin-like protein 3 (ANGPTL3) for treatment of homozygous familial hypercholesterolemia (HoFH) patients. This type of a rare disease can lead to increase of cholesterol as high as 1000 mg/dL and people suffering from it have already before the age of 20 signs and symptoms of atherosclerosis cardiovascular disease. This mAb inhibits lipoprotein lipase and endothelial lipase. The FDA status was based on positive interim Phase II results (from 4 patients) from last year.
Another Regeneron´s cholesterol-lowering drug co-developed with Sanofi, targeting PCSK9 and approved for heterozygous familial hypercholesterolemia (Praluent), is  not performing in sales as good as it was expected. Also, there are issues with patents and Amgen (Repatha).

Picture was created by using Wordclouds.com

Cholesterol, Brain-computer interface, Metabolomic profiles

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

My MedScan in cw 3/4
Winter is still not over, cross-country skiing is fantastic and warm drink with some power in will definitely increase heating from inside:-)

Here we go:

Cholesterol as a signalling agent

We all know a bad reputation of cholesterol and efforts to decrease it in order to beat cardiovascular diseases. Also, we know that without cholesterol, steroid hormones and cell walls could not be built. It is also known that cholesterol has regulatory functions in cell proliferation and development and its increase by high fat diet leads to increase of cancer incidence.

Scientists at the University of Illinois at Chicago by using a path-breaking optical imaging technique have shown where is cholesterol exactly located in the bilayer cell membrane and how it is moving within this area. They found by measuring in living cells that the outer membrane layer consists of 40% of cholesterol and the inner layer consists of just about 3% of cholesterol. “In response to a specific cell stimulus, the amount in the inner layer more than doubles, and the level in the outer layer drops by the same amount.”

Interestingly, they also found in more cancer cell lines that the percentage of cholesterol in the inner membrane layer is higher than in normal cells. This high presence in the inner membrane layer of cancer cells has been significantly decreased by statins, which to certain extent might contribute to the observed effect of statins on lowering of cancer incidence.

In the lab of Dr. Cho they developed some years ago an optical method that allows to quantify lipids in living cells. “They tagged a lipid-binding protein molecule with a fluorescent sensor that changes colour when it binds lipid. The colour-change indicates the ratio of bound to free lipid, letting them determine how much of the lipid is at a given location in the cell membrane.”

Brain-computer interface helped  paralysed people to communicate

Imagine that you are completely locked in your paralysed body, without possibility to move even with your eyes or without eye blinking. And your brain is still fully working. How to express your wishes, thoughts, needs, love? Such state is known as a completely lock-in syndrome and it means exactly how it sounds.

International team of researchers from Germany, Switzerland, China and USA managed by using a non-invasive brain-computer interface to get meaningful answers from completely locked-in people. And answers where obtained by thinking. It sounds like a sci-fi, does not it? It is not. And patients with amyotrophic lateral sclerosis could express even that they are happy despite extreme conditions. Somebody could at last listen to them.

What was the brain-computer interface used in this small study? It was near-infrared spectroscopy combined with electroencephalography, and blood oxygenation and electrical activity in brain were measured. The method of course needs to be used on higher number of people in order to conclude its effectiveness, these first results, thought, are very promising and bring hope for those who cannot communicate via other tools.

Metabolomic profiles as biomarkers of dietary composition

What we exactly eat is detectable by determination of certain metabolites in our blood. Researchers have created a metabolomic profile of obese people exposed to different diets and from this profile they correctly identified the test diet with more than 95% accuracy. Not only the adherence to certain dietary intervention in clinical trials can be thus checked, it can also bring more light on pathways linking diet to chronic diseases risk.

Clinical trials assessing certain dietary interventions usually suffer from relying on participant information and notes. But it is possible to figure out from blood what food groups were eaten. Using liquid chromatography-tandem mass spectrometry, American and Estonian researchers analysed 333 metabolites in a clinical trial and 152 identified to have different concentrations in different diets. Not surprising examples are diacylglycerols, triacylglycerols but also other metabolites were present such as branched-chain amino acids and markers reflecting metabolic status. “Analysis also suggest differential effects by diet on numerous cardiometabolic diseases risk factors”.

Metabolomics is one of the exciting and very informative scientific area. In connection to dietary intervention, there is not so many scientific articles, rising gradually in the recent 7 years. It will be interesting to have a look on findings here. Definitely, metabolomics has its stable seat in a biomarker area but of course also in drug development and basic understanding of physiology and cell biology.