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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”.

Source: http://jozefmacutek.wixsite.com/krajina

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, a 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, carrier. 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.

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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.

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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)”.

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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).

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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.

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Alzheimer´s Funding; $ 100 millions for start-ups; Eat fiber or be eaten; Open access policy

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 1/2
Freezing weather, a lot of snow, simply winter like I remember from my childhood, such have been recent weeks in my home.

Surprising or not, a sale ban on the novel PCSK9-targeted hypercholesterolemia drug Praluent (Sanofi, Regeneron) was released by the U.S federal judge in USA with a 30-day appeal period.

And, the most “Blue Monday” is already behind us, so it will be only better:-)

Here we go:

Alzheimer´s Funding Analyzer
A little bit older information, but still worthy to have a look. The Alzheimer´s Funding Analyzer (AFA), which is the service launched by the Journal of Alzheimer´s disease (JAD) now includes also grants from the Alzheimer´s Association. ”The AFA allows the end-user to conduct line-of-investigation queries (e.g., tau, ApoE4, vaccine) to look for funding trends and to see which investigators in which countries have been the most successful in obtaining funding for a given area of AD research.” Helpful, for free, and easy to use, however requiring registration and the JAD approval.

$ 100 millions is waiting for seed- and early-stage companies at intersection of math, physics, computing and biology
Digitalis, a venture fund from California, USA, announced launching of a new fund which will finance projects of seed- and early-stage companies at intersection of life sciences and computing. There is a clear gap for funding such projects. “The firm is also actively looking to co-found new companies that demonstrate promise in solving major health challenges”, with 3 investments already happened, as for example the Second genome leveraging a computational microbiome platform.

Your microbiota can eat you unless you do not eat enough fiber
Microbiome-related research and development activities are on rise in recent years. More than 7 000 scientific entries in PubMed in 2016 is more than 7-fold increase in comparison to 2010 on search terms like microbiota or microbiome. We are getting more information on how our microbiome contributes to our health and diseases. But still, we are at the beginning of this way. One cannot imagine that billions of foreign cells with all their genetic information, proteins and metabolites will be inert in our body. And they are not.

According to the paper published in the Cell by Luxembourg researchers, “fiber-deprived gut microbiota promotes aggressive colitis by enteric pathogen” and “low-fiber diet promotes expansion of colonic mucus-degrading bacteria”. Simply said, if we do not feed our microbiota by high-fiber foods, then they will look for nutrients in our mucus and damage our colonic mucus barrier. Interestingly, highly purified fibers like inulin which are often taken as prebiotic supplements, do not alleviate degradation of the mucus layer.

Immatics´ cancer deal with Amgen could be worth more than $ 1 Billion
Another small German biotech signed a deal with a big biotech company. After successful sale of the Ganymed Pharmaceuticals for EUR 422 millions with a possibility on future EUR 866 millions in contingent payments and the BioNTech entering a $ 310 millions plus milestones collaboration with Genentech last year, Immatics is another German biotech company succeeding in signing an agreement worthy possibly millions.

Immatics got thirty millions dollars as an upfront payment with possibilities to get more than $ 500 millions in milestones and further money in two-digit royalties from Amgen on developing next-generation T-cell engaging bispecific immunotherapies for multiple cancers. Both companies bring to this collaboration their unique technologies, Immatics their XPRESIDENT target discovery and T-cell receptor (TCR) platform and Amgen their Bispecific T-cell Engager (BiTE) technology.

Gates Foundation´s ban on publishing results in leading journals
Only a big player could push other big ones to change their rules. One of the most influential health charity does not allow to publish results of work funded by its money in journals which do not have an open-access policy like Nature, Science, New England Journal of Medicine and PNAS.

Gates Foundation argues that results of work funded by the organization should be available to all. Similar requests were in the past asked e.g by NIH and also by The Welcome Trust (allowing certain time embargo).

At the end, any funding body either private or public could ask for something similar which basically means that all papers should be freely accessible. When you think about it, it seems logical. Truth is, however, that open access in most cases does not come for free for authors. Journals could ask thousands of dollars in exchange to publish an article which is open for free for readers. Let´s see how all the activities and issues in many fields of scientific publishing industry end up.

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Cell vaccines; AFFiRiS´ PCSK9 and PD vaccines; Pfizer´s smoking cessation vaccine

This time I will scan selected vaccines against chronic and non-infectious diseases as appeared in my report (available also via this link). There should have been available results from about 20 Phase III to Phase I vaccine trials in 2016. And some interesting clinical trials started in 2016. Again, my selection is very subjective, not pretending to be comprehensive or representative. Just my selection. For more details you can go to my original report or to some of the posts published on my website.

Let´s have a look on 3 vaccine with 2016 milestones. I believe that success of infectious disease vaccines and saving of millions of lives can be translated also into vaccines for non-infectious indications and chronic diseases. In parallel to very complicated underlying basis of chronic diseases (in comparison to infectious diseases), it will be also a technology employed which matters in development of successful vaccines against chronic diseases. So far we have seen a lot of failures in this field. There are however also some optimistic news and still many vaccines in development in biotech, universities and pharma companies.

Algenpantucel-L vaccine against pancreatic cancer
Algenpantucel-L was an advanced cell vaccine in Phase III for treatment of pancreatic cancer in development at the company New Link Genetics. In May 2016 the company announced failure of the vaccine in the Phase III commercialization trial and shortly after that stopped all vaccine developments based on the same technology. They had also other candidates of the same technology in late development- Tergenpumatucel -L/Hyperacute® Lung for treatment of non-small-cell lung cancer (Phase II/III), HyperAcute® Prostate for treatment of prostate cancer (Phase I/II) and the combination vaccine Tergenpumatucel-L+indoximod (checkpoint inhibitor) for non-small cell lung cancer (Phase IB/II).

Algenpantucel-L consisted of 2 modified pancreatic cancer cell lines (HAPa-1 and HAPa-2) that have been modified to express a molecule α-gal. After immunization, pre-existing antibodies in humans against α-gal (which are thought to be a consequence from chronic immunological stimulation) immediately opsonized mouse pancreatic cells. α -gal epitopes are the major target of the hyperacute rejection response. This response occurs when organs are transplanted from lower animal donor species into primates and results in a rapid destruction of transplanted tissue and an augmented response against transplant antigens, including antigens not related to the α-gal epitopes. Such destroyed allogeneic pancreatic cancer cells are then processed by immune cells. Because cancer-specific antigens within the algenpantucel-L are shared by cancer cells in the patient, patient cancer cells were believed to be targeted by the immune system.

New Link Genetics is focused now on their other technology- inhibitors of the indoleamine 2,3-dioxygenase (IDO) pathway with two candidates. One candidate is licensed to Genentech. IDO pathway inhibitors belong to so called checkpoint inhibitors (like PD-1 or PD-L1). PD-1 checkpoint inhibitors Keytruda (Merck) and Opdivo (BMS) are both approved medicines in USA and in EU for more cancer indications.

AFFiRiS´PCSK9 and Parkinson´s disease vaccines
I cannot of course forget the peptide vaccines from my former employer AFFiRiS. Two PCSK9 vaccines AT04A and AT06A have different mode of action on the PCSK9 molecule.

Inhibition of PCSK9 was shown to decrease the “bad” LDL cholesterol (LDLc) which is involved in development of atherosclerosis and cardiovascular diseases (CVD). Two monoclonal antibodies against PCSK9 were approved by FDA and EC in 2015, however the trials to definitely confirm that decrease of LDLc by targeting PCSK9 is accompanied by an improved CVD rate, are still running.

Nevertheless, AFFiRiS PCSK9 vaccines, if they succeed, will have at least two big advantages over the expensive monoclonal antibodies treatment- a much lower price allowing also a preventive approach in a high proportion of population and an easy possibility to combine- e.g with vaccines against other “CVD” targets.

AT04A and AT06A are peptide vaccines consisting of a few amino acids sequences mimicking the original sequences of PCSK9 coupled to the carrier KLH and mixed with the adjuvant Alum. Both vaccines are B-cell vaccines, so the main mode of action is to induce, like normal infectious disease vaccines, antibodies in a body.

Despite the AT04A and AT06A trial should have been already finished in middle of 2016, AFFiRiS has so far not announced any results from this trial. It seems that the company is collecting data also from a “boost” study to provide more solid dataset, especially in the light of the promising results from their PD01A vaccine boost study (AFF008A) for treatment of Parkinson´s disease.

In the PD01A Phase I clinical trial, supported financially also by Michael J. Fox Foundation, “Immune Response was seen in 86% of patients, resulting in an increase of responder rate after boost immunization” and “PD01A-induced Antibodies Preferentially Bind to Fibrilic Alpha-Synuclein (aSyn)” as announced by the company in September 2016.

Pfizer´s vaccine(s) on smoking cessation
The Phase I trial on the PF-05402536 (NIC7-001) and PF-06413367 (NIC7-003) vaccines was already as of January 2016 marked as completed. Preclinical results from these vaccines on mice and primates were published in 2015 and also in 2016. The vaccines had been in the Pfizer´s pipeline still in August 2016 and then in the newest update, they are, or at least the PF-05402536, discontinued.

The PF-05402536/NIC7-001 vaccine was consisting of the NIC7 (peptide) coupled to the carrier molecule CRM197 and mixed with adjuvants Alum (AL(OH)3) and CpG (TLR9 agonist).

There are so far no results available from the Phase I study with the smoking cessation vaccines PF-05402536 and PF-06413367. Pfizer however published in 2016 very interesting results on how “Prior exposure to CRM or Qb-VLP significantly reduced subsequent responses to the conjugated antigen having the homologous carrier”. Qb-VLP is another carrier/adjuvant which is used, similarly as the CRM197, to induce an immune response by short molecules (haptens) which are normally not immunogenic. Such results showing the big negative effect of the “helping” carrier molecule on immune response against the antigen (which is THE target) can have very pronounced consequences and can be behind certain failures observed in this field.

Pfizer has been one of the few pharmaceutical companies which have vaccines inducing antibodies for treatment of chronic diseases in pipeline. Now, after discontinuing of PF-05402536, the only vaccine of such kind in their official pipeline is the PF-06753512/PrCa VBIR treatment which is a combination of multi-antigen vaccines, monoclonal antibody and a small molecule for treatment of prostate cancer. At least one vaccine in this regimen is a DNA vaccine since an electroporation device is also tested in this trial. Phase I trial is still recruiting patients and results are not expected before 2019. Fate of the Pfizer´s preclinical PCSK9 vaccine is not known to me.

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Cell Atlas; Creutzfeldt-Jakob disease; Profitable Biotechs; Artificial intelligence; HIV

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 cw49/50. As a gift were a few days spent in hot mineral waters just in middle of the hectic month. Let´s see whether in December announced positive results from the Biogen´s Phase Ib titration study with aducanumab will be translated into an Alzheimer´s drug, transforming our lives.
And, I wish you all very Merry Christmas spent with loved people and without stress.

Here we go:

Cell Atlas for all
Part of the Sweden-based Human Protein Atlas, the Cell Atlas, was launched in December. The Cell Atlas shows a location of more than 12 000 proteins in more than 30 cellular structures and opens the way for “spatial proteomics”. Basis for the Cell Atlas are 56 cell lines “selected to represent various cell populations in different organs of the human body”. Protein expression is accompanied by mRNA expression profile for all human genes.

What I find interesting is a possibility to submit antibodies and get recognized as an antibody provider fulfilling high Human Protein Atlas criteria as the antibodies are always carefully validated there. Furthermore, for proteins for which there are no other antibodies available, this validation is for free.

Early detection of Creutzfeldt-Jakob disease (CJD) from cerebrospinal fluid and nasal swabbing
Prion diseases as CJD can definitely be confirmed in brain tissue by CJD-specific abnormal prion protein (PrPCJD) presence. In between, CJD diagnosis employs a set of characteristics including presence of dementia, characteristic changes seen in EEG, presence of certain proteins in CSF and abnormalities in magnetic resonance imaging. Due to variable phenotypes of sporadic forms of CJD, sensitivity of diagnostic criteria for sporadic CJD based on the analysis of probable and definite cases has been 83%, with a specificity of 71%.

By introduction of the real-time quaking-induced conversion (RT-QuIC) assay which detects femtograms of PrPCJD from all subtypes of sporadic CJD, sensitivity and specificity has been increased. Italian scientists published recently a paper in JAMA introducing a diagnostic algorithm based on the RT-QuIC of PrPCJD from CSF and olfactory mucosa (OM) samples with introducing a gentle nasal swab procedure for OM. To date, for clinically suspected sporadic CJD their diagnostic flow provides a sensitivity and specificity of virtually 100%. A limitation of this study is that all patients were already symptomatic.

Most profitable Biotech companies
Three Biotech companies with the best operating margins, are according to the article in Biospace, United Therapeutics, Gilead Sciences and Biogen.

United Therapeutics as a leader in pulmonary arterial hypertension (PAH) with 5 drugs marketed has the most successful drug Remodulin, accounted for one third of the company revenue in 2016. Potential challenges to the company is patent expiration and entrance of generics in 2018.

Gilead Sciences is a leader in hepatitis C market, with Sovaldi and Harvoni “accounted for $ 20 billion in sales last year”. Gilead however also faces the biggest patent infringement issue in the U.S and after a jury decision on December 16th , it is ordered to pay to Merck about 10% of the hepatitis C drugs sales.

Biogen with its multiple sclerosis drugs Avonex and Tysabri enhanced by Tecfidera “maintain an industry-leading operating margins of 49,3% over the last 12 months”. As I already mentioned, a few days ago Biogen announced positive news from its Phase Ib study with an Alzheimer´s disease (AD) drug candidate aducanumab. A disease modifying or a preventive drug in AD will be, once found, worthy of tens billions of EUR.

Artificial intelligence helped discover new Amyotrophic Lateral Sclerosis genes (ALS)
Artificial intelligence (AI) represented by IBM Watson helped scientists from Barrow Neurological Institute identify new genes connected to ALS, a deadly neurodegenerative disease.

Top ranked genes from a gene set identified by the AI were further explored by the team of scientists and 8 genes proved to be associated with ALS. IBM Watson and a robust database behind accelerated gene identification which would normally took years, instead of a few months needed for the machine (and of course for people teaching a machine to learn).

And there is another work in biomedicine for artificial intelligence, as announced recently. The same system will help to identify basis behind cancer treatment resistance, for MIT´and Harvard´s Broad Institute in a 5-year, 5 million USD project.

HIV drugs linked to neurodegeneration
A paper from University of Pennsylvania published in the American Journal of Pathology brings evidences that certain HIV drugs known as protease inhibitors can have toxic effects on the central nervous system via increasing of BACE1 expression.

BACE is known to be involved in processing of the amyloid precursor protein APP into Aβ which is the main component of amyloid plaques, one of the culprits of Alzheimer´s disease pathology. BACE has been also a target of several AD drug candidates in pipeline. Another enzyme, PERK, has been found to be significantly involved in this process.

Bicykle as a drug, Biomedical big data; Our memories; Startups

Biotech deals; Bicykle as a drug, Biomedical big data; Our memories; Startups

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 47/48. Two weeks and so many interesting things that it was hard to choose only five. In area of my interests the most important information was another failure of Eli Lilly´s solanezumab, an Alzheimer´s disease drug candidate (monoclonal antibody) targeting Aβ. And, we are approaching quickly Christmas holidays as we enjoyed already the 2nd advent candle…

Here we go:

Billion-dollar biotech deals
Are you impressed by big numbers of many biotech deals? There is a lot of announcements at time of the deals signature. However, it is usually a well kept secret when an agreement is over after a few years or even a few months, not fulfilling all the milestones payments announced.  In-front payments of the deals are in many cases only a small part of the overal „possible“ deal. Upfront payments depend on a risk appetite of a licensee and willing of a biotech company to share development risks and uncertainties. Thought we can be still impressed by high upfront payments paid by some big pharma.

STAT analyzed nearly 700 biotech licensing deals inked over the past four years and found that biobucks hugely outweigh actual cash on the barrelhead. On average, just 14 percent of the total announced value was paid out upon signing“.

Bicykles as possible drugs
In light of the previous input, a company called Bicykle Therapeutics entered into a fantastic 1 billion deal with AstraZeneca. What interested me is the technology this company has offered to AZ. The company acquired a platform from MRC Laboratory of Molecular Biology in Cambridge, UK for identifying of proprietary bicyklic peptides,or Bicykles. „Bicycles® are a breakthrough new therapeutic class that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tuneable exposure and chemical synthesis“.

Bicykle Therapeutics develops „bicykle drug conjugates“ (BDC, e.g with toxins) in oncology field and shows higher availability and targeting of tumours than monoclonal antibodies.

Big data in Biomedical research
Are we sure that we are prepared for analysis of all biomedical data coming out of big trials, experiments, etc.? Many information and facts are already out there and are waiting. For open minded people, bioinformatics, data scientists, unbiased researchers, artificial intelligence…

„Biomedical research is going big-time: Megaprojects that collect vast stores of data are proliferating rapidly. But scientists’ ability to make sense of all that information isn’t keeping up.“ Try this article and see if you agree.

Memory and us
„Sophisticated techniques can decode stimulus representations for items held in a person’s working memory. However, when subjects shift their attention toward something else, the neural representation of the now unattended item drops to baseline, as though the item has been forgotten. Rose et al. used single-pulse transcranial magnetic stimulation (TMS) to briefly reactivate the representation of an unattended item. A short pulse of TMS enhanced recognition of “forgotten” stimuli, bringing an unattended item back into focal attention.“

The article published in Science brings interesting facts about our memory and forgetting. Try also other recent memory articles of Dr. Postle.

Medical Device startups
Atomwise is a startup medical device company developing supercomputers. Thought we can not directly account these as new medical devices today, this can be changed by tomorrow. „By using one of the world’s top supercomputers to analyse databases 1000 times larger than those of the past, Atomwise is delivering precise and reliable medicinal predictions. Their end goal is finding better medicines faster.“ Other worthy to watch medical device startups are introduced regularly by MedReps on their website.