Category Archives: medicine

Nanotechnology research protocols for Environment, Health and Safety Studies in US and a nanomedicine characterization laboratory in the European Union

I have two items relating to nanotechnology and the development of protocols. The first item concerns the launch of a new web portal by the US National Institute of Standards and Technology.

US National Institute of Standards and Technology (NIST)

From a July 1, 2015 news item on Azonano,

As engineered nanomaterials increasingly find their way into commercial products, researchers who study the potential environmental or health impacts of those materials face a growing challenge to accurately measure and characterize them. These challenges affect measurements of basic chemical and physical properties as well as toxicology assessments.

To help nano-EHS (Environment, Health and Safety)researchers navigate the often complex measurement issues, the National Institute of Standards and Technology (NIST) has launched a new website devoted to NIST-developed (or co-developed) and validated laboratory protocols for nano-EHS studies.

A July 1, 2015 NIST news release on EurekAlert, which originated the news item, offers more details about the information available through the web portal,

In common lab parlance, a “protocol” is a specific step-by-step procedure used to carry out a measurement or related activity, including all the chemicals and equipment required. Any peer-reviewed journal article reporting an experimental result has a “methods” section where the authors document their measurement protocol, but those descriptions are necessarily brief and condensed, and may lack validation of any sort. By comparison, on NIST’s new Protocols for Nano-EHS website the protocols are extraordinarily detailed. For ease of citation, they’re published individually–each with its own unique digital object identifier (DOI).

The protocols detail not only what you should do, but why and what could go wrong. The specificity is important, according to program director Debra Kaiser, because of the inherent difficulty of making reliable measurements of such small materials. “Often, if you do something seemingly trivial–use a different size pipette, for example–you get a different result. Our goal is to help people get data they can reproduce, data they can trust.”

A typical caution, for example, notes that if you’re using an instrument that measures the size of nanoparticles in a solution by how they scatter light, it’s important also to measure the transmission spectrum of the particles if they’re colored, because if they happen to absorb light strongly at the same frequency as your instrument, the result may be biased.

“These measurements are difficult because of the small size involved,” explains Kaiser. “Very few new instruments have been developed for this. People are adapting existing instruments and methods for the job, but often those instruments are being operated close to their limits and the methods were developed for chemicals or bulk materials and not for nanomaterials.”

“For example, NIST offers a reference material for measuring the size of gold nanoparticles in solution, and we report six different sizes depending on the instrument you use. We do it that way because different instruments sense different aspects of a nanoparticle’s dimensions. An electron microscope is telling you something different than a dynamic light scattering instrument, and the researcher needs to understand that.”

The nano-EHS protocols offered by the NIST site, Kaiser says, could form the basis for consensus-based, formal test methods such as those published by ASTM and ISO.

NIST’s nano-EHS protocol site currently lists 12 different protocols in three categories: sample preparation, physico-chemical measurements and toxicological measurements. More protocols will be added as they are validated and documented. Suggestions for additional protocols are welcome at nanoprotocols@nist.gov.

The next item concerns European nanomedicine.

CEA-LETI and Europe’s first nanomedicine characterization laboratory

A July 1, 2015 news item on Nanotechnology Now describes the partnership which has led to launch of the new laboratory,

CEA-Leti today announced the launch of the European Nano-Characterisation Laboratory (EU-NCL) funded by the European Union’s Horizon 2020 research and innovation programm[1]e. Its main objective is to reach a level of international excellence in nanomedicine characterisation for medical indications like cancer, diabetes, inflammatory diseases or infections, and make it accessible to all organisations developing candidate nanomedicines prior to their submission to regulatory agencies to get the approval for clinical trials and, later, marketing authorization.

“As reported in the ETPN White Paper[2], there is a lack of infrastructure to support nanotechnology-based innovation in healthcare,” said Patrick Boisseau, head of business development in nanomedicine at CEA-Leti and chairman of the European Technology Platform Nanomedicine (ETPN). “Nanocharacterisation is the first bottleneck encountered by companies developing nanotherapeutics. The EU-NCL project is of most importance for the nanomedicine community, as it will contribute to the competiveness of nanomedicine products and tools and facilitate regulation in Europe.”

EU-NCL is partnered with the sole international reference facility, the Nanotechnology Characterization Lab of the National Cancer Institute in the U.S. (US-NCL)[3], to get faster international harmonization of analytical protocols.

“We are excited to be part of this cooperative arrangement between Europe and the U.S.,” said Scott E. McNeil, director of U.S. NCL. “We hope this collaboration will help standardize regulatory requirements for clinical evaluation and marketing of nanomedicines internationally. This venture holds great promise for using nanotechnologies to overcome cancer and other major diseases around the world.”

A July 2, 2015 EMPA (Swiss Federal Laboratories for Materials Science and Technology) news release on EurekAlert provides more detail about the laboratory and the partnerships,

The «European Nanomedicine Characterization Laboratory» (EU-NCL), which was launched on 1 June 2015, has a clear-cut goal: to help bring more nanomedicine candidates into the clinic and on the market, for the benefit of patients and the European pharmaceutical industry. To achieve this, EU-NCL is partnered with the sole international reference facility, the «Nanotechnology Characterization Laboratory» (US-NCL) of the US-National Cancer Institute, to get faster international harmonization of analytical protocols. EU-NCL is also closely connected to national medicine agencies and the European Medicines Agency to continuously adapt its analytical services to requests of regulators. EU-NCL is designed, organized and operated according to the highest EU regulatory and quality standards. «We are excited to be part of this cooperative project between Europe and the U.S.,» says Scott E. McNeil, director of US-NCL. «We hope this collaboration will help standardize regulatory requirements for clinical evaluation and marketing of nanomedicines internationally. This venture holds great promise for using nanotechnologies to overcome cancer and other major diseases around the world.»

Nine partners from eight countries

EU-NCL, which is funded by the EU for a four-year period with nearly 5 million Euros, brings together nine partners from eight countries: CEA-Tech in Leti and Liten, France, the coordinator of the project; the Joint Research Centre of the European Commission in Ispra, Italy; European Research Services GmbH in Münster Germany; Leidos Biomedical Research, Inc. in Frederick, USA; Trinity College in Dublin, Ireland; SINTEF in Oslo, Norway; the University of Liverpool in the UK; Empa, the Swiss Federal Laboratories for Materials Science and Technology in St. Gallen, Switzerland; Westfälische Wilhelms-Universität (WWU) and Gesellschaft für Bioanalytik, both in Münster, Germany. Together, the partnering institutions will provide a trans-disciplinary testing infrastructure covering a comprehensive set of preclinical characterization assays (physical, chemical, in vitro and in vivo biological testing), which will allow researchers to fully comprehend the biodistribution, metabolism, pharmacokinetics, safety profiles and immunological effects of their medicinal nano-products. The project will also foster the use and deployment of standard operating procedures (SOPs), benchmark materials and quality management for the preclinical characterization of medicinal nano-products. Yet another objective is to promote intersectoral and interdisciplinary communication among key drivers of innovation, especially between developers and regulatory agencies.

The goal: to bring safe and efficient nano-therapeutics faster to the patient

Within EU-NCL, six analytical facilities will offer transnational access to their existing analytical services for public and private developers, and will also develop new or improved analytical assays to keep EU-NCL at the cutting edge of nanomedicine characterization. A complementary set of networking activities will enable EU-NCL to deliver to European academic or industrial scientists the high-quality analytical services they require for accelerating the industrial development of their candidate nanomedicines. The Empa team of Peter Wick at the «Particles-Biology Interactions» lab will be in charge of the quality management of all analytical methods, a key task to guarantee the best possible reproducibility and comparability of the data between the various analytical labs within the consortium. «EU-NCL supports our research activities in developing innovative and safe nanomaterials for healthcare within an international network, which will actively shape future standards in nanomedicine and strengthen Empa as an enabler to facilitate the transfer of novel nanomedicines from bench to bedside», says Wick.

You can find more information about the laboratory on the Horizon 2020 (a European Union science funding programme) project page for the EU-NCL laboratory. For anyone curious about CEA-Leti, it’s a double-layered organization. CEA is France’s Commission on Atomic Energy and Alternative Energy (Commissariat à l’énergie atomique et aux énergies alternatives); you can go here to their French language site (there is an English language clickable option on the page). Leti is one of the CEA’s institutes and is known as either Leti or CEA-Leti. I have no idea what Leti stands for. Here’s the Leti website (this is the English language version).

Informal roundup of robot movies and television programmes and a glimpse into our robot future

David Bruggeman has written an informal series of posts about robot movies. The latest, a June 27, 2015 posting on his Pasco Phronesis blog, highlights the latest Terminator film and opines that the recent interest could be traced back to the rebooted Battlestar Galactica television series (Note: Links have been removed),

I suppose this could be traced back to the reboot of Battlestar Galactica over a decade ago, but robots and androids have become an increasing presence on film and television, particularly in the last 2 years.

In the movies, the new Terminator film comes out next week, and the previews suggest we will see a new generation of killer robots traveling through time and space.  Chappie is now out on your digital medium of choice (and I’ll post about any science fiction science policy/SciFiSciPol once I see it), so you can compare its robot police to those from either edition of Robocop or the 2013 series Almost Human.  Robots also have a role …

The new television series he mentions, Humans (click on About) debuted on the US tv channel, AMC, on Sunday, June 28, 2015 (yesterday).

HUMANS is set in a parallel present, where the latest must-have gadget for any busy family is a Synth – a highly-developed robotic servant, eerily similar to its live counterpart. In the hope of transforming the way his family lives, father Joe Hawkins (Tom Goodman-Hill) purchases a Synth (Gemma Chan) against the wishes of his wife (Katharine Parkinson), only to discover that sharing life with a machine has far-reaching and chilling consequences.

Here’s a bit more information from its Wikipedia entry,

Humans (styled as HUM∀NS) is a British-American science fiction television series, debuted in June 2015 on Channel 4 and AMC.[2] Written by the British team Sam Vincent and Jonathan Brackley, based on the award-winning Swedish science fiction drama Real Humans, the series explores the emotional impact of the blurring of the lines between humans and machines. The series is produced jointly by AMC, Channel 4 and Kudos.[3] The series will consist of eight episodes.[4]

David also wrote about Ex Machina, a recent robot film with artistic ambitions, in an April 26, 2015 posting on his Pasco Phronesis blog,

I finally saw Ex Machina, which recently opened in the United States.  It’s a minimalist film, with few speaking roles and a plot revolving around an intelligence test.  Of the robot movies out this year, it has received the strongest reviews, and it may take home some trophies during the next awards season.  Shot in Norway, the film is both lovely to watch and tricky to engage.  I finished the film not quite sure what the characters were thinking, and perhaps that’s a lesson from the film.

Unlike Chappie and Automata, the intelligent robot at the center of Ex Machina is not out in the world. …

He started the series with a Feb. 8, 2015 posting which previews the movies in his later postings but also includes a couple of others not mentioned in either the April or June posting, Avengers: Age of Ultron and Spare Parts.

It’s interesting to me that these robots  are mostly not related to the benign robots in the movie, ‘Forbidden Planet’, a reworking of Shakespeare’s The Tempest in outer space, in ‘Lost in Space’, a 1960s television programme, and in the Jetsons animated tv series of the 1960s. As far as I can tell not having seen the new movies in question, the only benign robot in the current crop would be ‘Chappie’. It should be mentioned that the ‘Terminator’, in the person of Arnold Schwarzenegger, has over a course of three or four movies evolved from a destructive robot bent on evil to a destructive robot working on behalf of good.

I’ll add one more more television programme and I’m not sure if the robot boy is good or evil but there’s Extant where Halle Berry’s robot son seems to be in a version of the Pinocchio story (an ersatz child want to become human), which is enjoying its second season on US television as of July 1, 2015.

Regardless of one or two ‘sweet’ robots, there seems to be a trend toward ominous robots and perhaps, in addition to Battlestar Galactica, the concerns being raised by prominent scientists such as Stephen Hawking and those associated with the Centre for Existential Risk at the University of Cambridge have something to do with this trend and may partially explain why Chappie did not do as well at the box office as hoped. Thematically, it was swimming against the current.

As for a glimpse into the future, there’s this Children’s Hospital of Los Angeles June 29, 2015 news release,

Many hospitals lack the resources and patient volume to employ a round-the-clock, neonatal intensive care specialist to treat their youngest and sickest patients. Telemedicine–with real-time audio and video communication between a neonatal intensive care specialist and a patient–can provide access to this level of care.

A team of neonatologists at Children’s Hospital Los Angeles investigated the use of robot-assisted telemedicine in performing bedside rounds and directing daily care for infants with mild-to-moderate disease. They found no significant differences in patient outcomes when telemedicine was used and noted a high level of parent satisfaction. This is the first published report of using telemedicine for patient rounds in a neonatal intensive care unit (NICU). Results will be published online first on June 29 in the Journal of Telemedicine and Telecare.

Glimpse into the future?

The part I find most fascinating was that there was no difference in outcomes, moreover, the parents’ satisfaction rate was high when robots (telemedicine) were used. Finally, of the families who completed the after care survey (45%), all indicated they would be comfortable with another telemedicine (robot) experience. My comment, should robots prove to be cheaper in the long run and the research results hold as more studies are done, I imagine that hospitals will introduce them as a means of cost cutting.

Mexican company “Medical and Surgical Center for Retina” and its painless eye drop treatment

I am confined to the materials which have been translated into English so this story is lighter on detail than I would prefer. A June 26, 2015 news item on Azonano describes a company which provides a new painless treatment for secondary blindness,

The Mexican company “Medical and Surgical Center for Retina” created a way to transport drugs, in order to avoid risks and painful treatments in people with secondary blindness due to chronic degenerative blindness such as diabetic retinopathy and degeneration of the eye. The innovative formula results eliminates the need to administrate the drug by intraocular injection.

It is a nanotechnology product, which works with last generation liposomes particles, concentrated in droplets, which function as a conveyor that wraps proteins or antibody fragments and allow its passage into the eye. Once inside, it releases the drugs.

With the nanotechnology product the costs are reduced by 80 to 90 percent and enables the elderly population to make use of it. “With this technology hospitals that have no resources can apply the needed drugs, without requiring a a specialist or a particular facility for the administration. It is necessary to be prescribed by a physician, but it can be administered at home, which lowers the cost. “

A June 25, 2015 Investigación y Desarrollo news release on Alpha Galileo, which originated the news item, provides more information about the company and what seems to be a series of clinical trials both current and upcoming,

The doctor Juan Carlos Altamirano Vallejo, medical director of the Medical and Surgical Center for Retina, mentions that the conditions that originate in the retina are mostly caused by chronic degenerative diseases such as diabetes (diabetic retinopathy) or macular alteration . Patients with this conditions usually require one injection per month which comes at a very high cost and increases if the procedure is needed for both eyes.

The company, located in Jalisco (central west state of Mexico) won the Mexican National Prize for Technology and Innovation and plans to conclude the Clinical Research regulated by the Federal Commission for Protection Against Health Risks (COFEPRIS) next year. The idea is for the medicine to be distributed in state and private health institutions. So far, the achieved results are the same as the ones obtained with intraocular injection, but without the inherent risks of this procedure, such as infection or retinal detachment.

Current talks are being held with COFEPRIS to conduct a study within several diseases and increase its use for different conditions. In the United States, patients who have followed the treatment have had positive results.

The Medical and Surgical Center for Retina provides medical care and a specialized retina Ophthalmology Clinic provides consultation, which also has an area of ​​Biotechnology and Drug Research of Biomedical Engineering, Diagnosis and Treatment Equipment.

Altamirano Vallejo says that receiving the award opens the doors to reach more people and prevent blindness. “It is the most important prize delivered by the Presidency of the Republic in the area of ​​technology and innovation. For us, to have an entity such as the award foundation to guide us and allows us to learn, know skills, strengths and company administration makes us proud, specially the opportunity for a product like this to reach the market and prevent blindness.

Back in an Oct. 9, 2014 posting, I wrote about a couple of nanotechnology-enabled eye drop projects and some of the challenges with trying to bypass the eye’s natural protections.

Finally, I was not able to locate the company (without the Spanish language name that’s not likely to be easy) but there is more information about Investigación y Desarrollo here.

Crowdfund nano spies for cancer

University of Groningen (Netherlands) researcher, Romana Schirhagl, is crowdfunding her development of a new technique (using nanodiamonds) for biomedical research which would allow observation of free radicals in cells. From a June 25, 2015 news item on Nanowerk,

Romana Schirhagl, a researcher at the University Medical Center Groningen, is hoping to garner public support for a new form of cancer research. Schirhagl wants to introduce miniscule diamonds into living cancer cells. Like spies, these nanodiamonds will be on a mission to reveal the secrets of the cell. Schirhagl applies a unique combination of knowledge and techniques from physics, chemistry and medicine in the research. This could form the basis of new and improved cancer drugs.

A June 16, 2015 University of Groningen press release, which originated the news item, provides background information for the research,

The research of Schirhagl and her research group in the department of Biomedical Engineering focuses on the behaviour of free radicals in a cell. These radicals have an important role in the body. They are sometimes extremely useful, as in the immune system, where they help fight bacteria and viruses, but sometimes very harmful, as when they actually harm healthy cells and can cause cancer. As the radicals only exist for a fraction of a second, it is difficult to tell them apart and study them.

New technique

Schirhagl wants to apply a new technique that currently is mainly used in fundamental physics but looks extremely promising for biomedical research. The technique is based on very small diamonds that can ‘sense’ the presence of magnetic fields from the radicals. The nanodiamonds are fluorescent and change in luminosity as a response to their environment. This makes it easier to determine which radicals occur when and how they work. This information should make it possible to improve cancer drugs – which themselves sometimes use free radicals – or even develop new ones.

Unexpectedly, the crowdfunding platform is the University of Groningen’s own. You can find out more about Nano spies here. To date the project has raised over 6,600 Euros towards a goal of 20,000 Euros.

A pragmatic approach to alternatives to animal testing

Retitled and cross-posted from the June 30, 2015 posting (Testing times: the future of animal alternatives) on the International Innovation blog (a CORDIS-listed project dissemination partner for FP7 and H2020 projects).

Maryse de la Giroday explains how emerging innovations can provide much-needed alternatives to animal testing. She also shares highlights of the 9th World Congress on Alternatives to Animal Testing.

‘Guinea pigging’ is the practice of testing drugs that have passed in vitro and in vivo tests on healthy humans in a Phase I clinical trial. In fact, healthy humans can make quite a bit of money as guinea pigs. The practice is sufficiently well-entrenched that there is a magazine, Guinea Pig Zero, devoted to professionals. While most participants anticipate some unpleasant side effects, guinea pigging can sometimes be a dangerous ‘profession’.

HARMFUL TO HEALTH

One infamous incident highlighting the dangers of guinea pigging occurred in 2006 at Northwick Park Hospital outside London. Volunteers were offered £2,000 to participate in a Phase I clinical trial to test a prospective treatment – a monoclonal antibody designed for rheumatoid arthritis and multiple sclerosis. The drug, called TGN1412, caused catastrophic systemic organ failure in participants. All six individuals receiving the drug required hospital treatment. One participant reportedly underwent amputation of fingers and toes. Another reacted with symptoms comparable to John Merrick, the Elephant Man.

The root of the disaster lay in subtle immune system differences between humans and cynomolgus monkeys – the model animal tested prior to the clinical trial. The drug was designed for the CD28 receptor on T cells. The monkeys’ receptors closely resemble those found in humans. However, unlike these monkeys, humans have other immune cells that carry CD28. The trial participants received a starting dosage that was 0.2 per cent of what the monkeys received in their final tests, but failure to take these additional receptors into account meant a dosage that was supposed to occupy 10 per cent of the available CD28 receptors instead occupied 90 per cent. After the event, a Russian inventor purchased the commercial rights to the drug and renamed it TAB08. It has been further developed by Russian company, TheraMAB, and TAB08 is reportedly in Phase II clinical trials.

HUMAN-ON-A-CHIP AND ORGANOID PROJECTS

While animal testing has been a powerful and useful tool for determining safe usage for pharmaceuticals and other types of chemicals, it is also a cruel and imperfect practice. Moreover, it typically only predicts 30-60 per cent of human responses to new drugs. Nanotechnology and other emerging innovations present possibilities for reducing, and in some cases eliminating, the use of animal models.

People for the Ethical Treatment of Animals (PETA), still better known for its publicity stunts, maintains a webpage outlining a number of alternatives including in silico testing (computer modelling), and, perhaps most interestingly, human-on-a-chip and organoid (tissue engineering) projects.

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

Another interesting alternative for animal testing is organoids – a feature in regenerative medicine that can function as test sites. Engineers based at Cornell University recently published a paper on their functional, synthetic immune organ. Inspired by the lymph node, the organoid is comprised of gelatin-based biomaterials, which are reinforced with silicate nanoparticles (to keep the tissue from melting when reaching body temperature) and seeded with cells allowing it to mimic the anatomical microenvironment of a lymphatic node. It behaves like its inspiration converting B cells to germinal centres which activate, mature and mutate antibody genes when the body is under attack. The engineers claim to be able to control the immune response and to outperform 2D cultures with their 3D organoid. If the results are reproducible, the organoid could be used to develop new therapeutics.

Maryse de la Giroday is a science communications consultant and writer.

Full disclosure: Maryse de la Giroday received transportation and accommodation for the 9th World Congress on Alternatives to Animal Testing from SEURAT-1, a European Union project, making scientific inquiries to facilitate the transition to animal testing alternatives, where possible.

ETA July 1, 2015: I would like to acknowledge more sources for the information in this article,

Sources:

The guinea pigging term, the ‘professional aspect, the Northwick Park story, and the Guinea Pig Zero magazine can be found in Carl Elliot’s excellent 2006 story titled ‘Guinea-Pigging’ for New Yorker magazine.

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

Information about the drug used in the Northwick Park Hospital disaster, the sale of the rights to a Russian inventor, and the June 2015 date for the current Phase II clinical trials were found in this Wikipedia essay titled, TGN 1412.

http://en.wikipedia.org/wiki/TGN1412

Additional information about the renamed drug, TAB08 and its Phase II clinical trials was found on (a) a US government website for information on clinical trials, (b) in a Dec. 2014 (?) TheraMAB  advertisement in a Nature group magazine and a Jan. 2014 press release,

https://www.clinicaltrials.gov/ct2/show/NCT01990157?term=TAB08_RA01&rank=1

http://www.theramab.ru/TheraMAB_NAture.pdf

http://theramab.ru/en/news/phase_II

An April 2015 article (Experimental drug that injured UK volunteers resumes in human trials) by Owen Dyer for the British Medical Journal also mentioned the 2015 TheraMab Phase II clinical trials and provided information about the information about Macaque (cynomolgus) monkey tests.

http://www.bmj.com.proxy.lib.sfu.ca/content/350/bmj.h1831

BMJ 2015; 350 doi: http://dx.doi.org.proxy.lib.sfu.ca/10.1136/bmj.h1831 (Published 02 April 2015) Cite this as: BMJ 2015;350:h1831

A 2009 study by Christopher Horvath and Mark Milton somewhat contradicts the Dyer article’s contention that a species Macaque monkey was used as an animal model. (As the Dyer article is more recent and the Horvath/Milton analysis is more complex covering TGN 1412 in the context of other MAB drugs and their precursor tests along with specific TGN 1412 tests, I opted for the simple description.)

The TeGenero Incident [another name for the Northwick Park Accident] and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? by Christopher J. Horvath and Mark N. Milton. Published online before print February 24, 2009, doi: 10.1177/0192623309332986 Toxicol Pathol April 2009 vol. 37 no. 3 372-383

http://tpx.sagepub.com/content/37/3/372.full

Philippa Roxbuy’s May 24, 2013 BBC news online article provided confirmation and an additional detail or two about the Northwick Park Hospital accident. It notes that other models, in addition to animal models, are being developed.

http://www.bbc.com/news/health-22556736

Anne Ju’s excellent June 10,2015 news release about the Cornell University organoid (synthetic immune organ) project was very helpful.

http://www.news.cornell.edu/stories/2015/06/engineers-synthetic-immune-organ-produces-antibodies

There will also be a magazine article in International Innovation, which will differ somewhat from the blog posting, due to editorial style and other requirements.

Clinical trial for bionic eye (artificial retinal implant) shows encouraging results (safety and efficacy)

The Argus II artificial retina was first mentioned here in a Feb. 15, 2013 posting (scroll down about 50% of the way) when it received US Food and Drug Administration (FDA) commercial approval. In retrospect that seems puzzling since the results of a three-year clinical trial have just been reported in a June 23, 2015 news item on ScienceDaily (Note: There was one piece of information about the approval which didn’t make its way into the information disseminated in 2013),

The three-year clinical trial results of the retinal implant popularly known as the “bionic eye,” have proven the long-term efficacy, safety and reliability of the device that restores vision in those blinded by a rare, degenerative eye disease. The findings show that the Argus II significantly improves visual function and quality of life for people blinded by retinitis pigmentosa. They are being published online in Ophthalmology, the journal of the American Academy of Ophthalmology.

A June 23, 2015 American Academy of Ophthalmology news release (also on EurekAlert), which originated the news item, describes the condition the Argus II is designed for and that crucial bit of FDA information,

Retinitis pigmentosa is an incurable disease that affects about 1 in 4,000 Americans and causes slow vision loss that eventually leads to blindness.[1] The Argus II system was designed to help provide patients who have lost their sight due to the disease with some useful vision. Through the device, patients with retinitis pigmentosa are able to see patterns of light that the brain learns to interpret as an image. The system uses a miniature video camera stored in the patient’s glasses to send visual information to a small computerized video processing unit which can be stored in a pocket. This computer turns the image to electronic signals that are sent wirelessly to an electronic device implanted on the retina, the layer of light-sensing cells lining the back of the eye.

The Argus II received Food and Drug Administration (FDA) approval as a Humanitarian Use Device (HUD) in 2013, which is an approval specifically for devices intended to benefit small populations and/or rare conditions. [emphasis mine]

I don’t recall seeing “Humanitarian Use Device (HUD)” in the 2013 materials which focused on the FDA’s commercial use approval. I gather from this experience that commercial use doesn’t necessarily mean they’ve finished with clinical trials and are ready to start selling the product. In any event, I will try to take a closer look at the actual approvals the next time, assuming I can make sense of the language.

After all the talk about it, here’s what the device looks like,

 Caption: Figure A, The implanted portions of the Argus II System. Figure B, The external components of the Argus II System. Images in real time are captured by camera mounted on the glasses. The video processing unit down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radiofrequency link form the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the system. Credit: Photo courtesy of Second Sight Medical Products, Inc.


Caption: Figure A, The implanted portions of the Argus II System. Figure B, The external components of the Argus II System. Images in real time are captured by camera mounted on the glasses. The video processing unit down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radiofrequency link form the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the system.
Credit: Photo courtesy of Second Sight Medical Products, Inc.

The news release offers more details about the recently completed clinical trial,

To further evaluate the safety, reliability and benefit of the device, a clinical trial of 30 people, aged 28 to 77, was conducted in the United States and Europe. All of the study participants had little or no light perception in both eyes. The researchers conducted visual function tests using both a computer screen and real-world conditions, including finding and touching a door and identifying and following a line on the ground. A Functional Low-vision Observer Rated Assessment (FLORA) was also performed by independent visual rehabilitation experts at the request of the FDA to assess the impact of the Argus II system on the subjects’ everyday lives, including extensive interviews and tasks performed around the home.

The visual function results indicated that up to 89 percent of the subjects performed significantly better with the device. The FLORA found that among the subjects, 80 percent received benefit from the system when considering both functional vision and patient-reported quality of life, and no subjects were affected negatively.

After one year, two-thirds of the subjects had not experienced device- or surgery-related serious adverse events. After three years, there were no device failures. Throughout the three years, 11 subjects experienced serious adverse events, most of which occurred soon after implantation and were successfully treated. One of these treatments, however, was to remove the device due to recurring erosion after the suture tab on the device became damaged.

“This study shows that the Argus II system is a viable treatment option for people profoundly blind due to retinitis pigmentosa – one that can make a meaningful difference in their lives and provides a benefit that can last over time,” said Allen C. Ho, M.D., lead author of the study and director of the clinical retina research unit at Wills Eye Hospital. “I look forward to future studies with this technology which may make possible expansion of the intended use of the device, including treatment for other diseases and eye injuries.”

Here’s a link to a PDF of and a citation for the paper,

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind by Allen C. Ho,Mark S. Humayun, Jessy D. Dorn, Lyndon da Cruz, Gislin Dagnelie,James Handa, Pierre-Olivier Barale, José-Alain Sahel, Paulo E. Stanga, Farhad Hafezi, Avinoam B. Safran, Joel Salzmann, Arturo Santos, David Birch, Rand Spencer, Artur V. Cideciyan, Eugene de Juan, Jacque L. Duncan, Dean Eliott, Amani Fawzi, Lisa C. Olmos de Koo, Gary C. Brown, Julia A. Haller, Carl D. Regillo, Lucian V. Del Priore, Aries Arditi, Duane R. Geruschat, Robert J. Greenberg. Opthamology, June 2015 http://dx.doi.org/10.1016/j.ophtha.2015.04.032

This paper is open access.

Job posting (post doc in tissue engineering [organ-on-a-chip]) for the Istituto Italiano di Technologia

Here’s the posting (deadline is July 19, 2015),

Istituto Italiano di Tecnologia (IIT), Genova, Italy (http://www.iit.it) is a private law Foundation, created with special Government Law no. 269 dated September 30th 2003 with the objective of promoting Italy’s technological development and higher education in science and technology. Research at IIT is carried out in highly innovative scientific fields with state-of-the-art technology.

A post-doc position to develop “Organs-on-Chips” is available in the Laboratory of Nanotechnology for Precision Medicine at IIT.

Candidates should have a PhD in Tissue Engineering or closely related fields and an excellent publication record and should be highly motivated to work in an interdisciplinary team.

The candidate will work on the development of microfluidic-based organs-on-chips.

These microchips will be used to recapitulate the microarchitecture and functions of living organs and pathological tissues such as cancer and will possibly form an accurate alternative to traditional animal testing and enable high-throughput screening of drugs and nanomedicines.

The candidate should have:

  • strong skills in tissue engineering as well as in molecular, cellular and in vivo tumor biology;
  • documented experience in primary cell culture and analysis;
  • excellent oral and written communication skills in English and the ability to work both independently and as part of a multidisciplinary team.

Interested applicants should contact directly Dr. Paolo Decuzzi ( paolo.decuzzi@iit.it) for any informal queries.

For a formal application  please send CV, list of publications with Impact Factor and names and email addresses of 2 referees to applications@iit.it

Please apply by July 19, 2015 quoting “Post doc position in Tissue Engineering” in the mail subject. [emphasis mine]

In order to comply with Italian law (art. 23 of Privacy Law of the Italian Legislative Decree n. 196/03), the candidate is kindly asked to give his/her consent to allow Istituto Italiano di Tecnologia to process his/her personal data.

We inform you that the information you provide will be solely used for the purpose of evaluating and selecting candidates in order to meet the requirements of Istituto Italiano di Tecnologia.

Your data will be processed by Istituto Italiano di Tecnologia, with its headquarters in Genoa, Via Morego 30, acting as the Data Holder, using computer and paper-based means, observing the rules on the protection of personal data, including those relating to the security of data, and they will not be communicated to thirds.

Please also note that, pursuant to art.7 of Legislative Decree 196/2003, you may exercise your rights at any time as a party concerned by contacting the Data Holder.

Istituto Italiano di Tecnologia is an Equal Opportunity Employer that actively seeks diversity in the workforce.

Don’t forget when preparing your application, should you be living on the West Coast of Canada or the US (not sure about Mexico as its coast veers east somewhat), Italy is +9 hours . This means you’d best get your application submitted by 3 pm PST on July 19, 2015.

Herbicide nanometric sensor could help diagnose multiple sclerosis

This research into nanometric sensors and multiple sclerosis comes from Brazil. According to a June 23, 2015 news item on Nanowerk (Note: A link has been removed),

The early diagnosis of certain types of cancer, as well as nervous system diseases such as multiple sclerosis and neuromyelitis optica, may soon be facilitated by the use of a nanosensor capable of identifying biomarkers of these pathological conditions (“A Nanobiosensor Based on 4-Hydroxyphenylpyruvate Dioxygenase Enzyme for Mesotrione Detection”).

The nanobiosensor was developed at the Federal University of São Carlos (UFSCar), Sorocaba, in partnership with the São Paulo Federal Institute of Education, Science & Technology (IFSP), Itapetininga, São Paulo State, Brazil. It was originally designed to detect herbicides, heavy metals and other pollutants.

A June 23, 2015 Fundação de Amparo à Pesquisa do Estado de São Paulo news release on EurekAlert, which originated the news item, describes the sensor as it was originally used and explains its new function as a diagnostic tool for multiple sclerosis and other diseases,

“It’s a highly sensitive device, which we developed in collaboration with Alberto Luís Dario Moreau, a professor at IFSP. “We were able to increase sensitivity dramatically by going down to the nanometric scale,” said physicist Fábio de Lima Leite, a professor at UFSCar and the coordinator of the research group.

The nanobiosensor consists of a silicon nitride (Si3N4) or silicon (Si) nanoprobe with a molecular-scale elastic constant and a nanotip coupled to an enzyme, protein or other molecule.

When this molecule touches a target of interest, such as an antibody or antigen, the probe bends as the two molecules adhere. The deflection is detected and measured by the device, enabling scientists to identify the target.

“We started by detecting herbicides and heavy metals. Now we’re testing the device for use in detecting target molecules typical of nervous system diseases, in partnership with colleagues at leading centers of research on demyelinating diseases of the central nervous system”

The migration from herbicide detection to antibody detection was motivated mainly by the difficulty of diagnosing demyelinating diseases, cancer and other chronic diseases before they have advanced beyond an initial stage.

The criteria for establishing a diagnosis of multiple sclerosis or neuromyelitis optica are clinical (supplemented by MRI scans), and patients do not always present with a characteristic clinical picture. More precise diagnosis entails ruling out several other diseases.

The development of nanodevices will be of assistance in identifying these diseases and reducing the chances of false diagnosis.

The procedure can be as simple as placing a drop of the patient’s cerebrospinal fluid on a glass slide and observing its interaction with the nanobiosensor.

“If the interaction is low, we’ll be able to rule out multiple sclerosis with great confidence,” Leite said. “High interaction will indicate that the person is very likely to have the disease.” In this case, further testing would be required to exclude the possibility of a false positive.

“Different nervous system diseases have highly similar symptoms. Multiple sclerosis and neuromyelitis optica are just two examples. Even specialists experience difficulties or take a long time to diagnose them. Our technique would provide a differential diagnostic tool,” Leite said.

The next step for the group is to research biomarkers for these diseases that have not been completely mapped, including antibodies and antigens, among others. The group has begun tests for the detection of head and neck cancer.

Here’s a link to and a citation for the paper,

A Nanobiosensor Based on 4-Hydroxyphenylpyruvate Dioxygenase Enzyme for Mesotrione Detection by P. Soto Garcia, A.L.D Moreau, J.C. Magalhaes Ierich,  A.C Araujo Vig, A.M. Higa, G.S. Oliveira, F. Camargo Abdalla, M. Hausen, & F.L. Leite. Sensors Journal, IEEE  (Volume:15 ,  Issue: 4) pp. 2106 – 2113 Date of Publication: 20 November 2014 Date of Current Version: 27 January 2015 Issue Date: April 2015  DOI 10.1109/JSEN.2014.2371773

This paper is behind a paywall.

Knight Therapeutics, a Canadian pharmaceutical company, enters agreement with Russia’s (?) Pro Bono Bio, a nanotechnology product company

The June 27, 2015 news item on Nanotechnology Now includes two pieces of business news (I am more interested in the second),

Knight Therapeutics Inc. (TSX:GUD) (“Knight” or the “Company”), a leading Canadian specialty pharmaceutical company, announced today that it has (1) extended a secured loan of US$15 million to Pro Bono Bio PLC (“Pro Bono Bio”), the world’s leading healthcare nanotechnology company, and (2) entered into an exclusive distribution agreement with Pro Bono Bio to commercialize its wide range of nanotechnology products, medical devices and drug delivery technologies in select territories.

A June 26, 2015 Knight Pharmaceuticals news release, which originated the news item, provides a few more details about the loan and the license agreement,

The secured loan of US$15 million, which matures on June 25, 2018, will bear interest at 12% per annum plus other additional consideration. The interest rate will decrease to 10% if Pro Bono Bio meets certain equity-fundraising targets. The loan is secured by a charge over the assets of Pro Bono Bio and its affiliates which includes but is not limited to Flexiseq™, an innovative topical pain product that has sales of more than 3 million units since its U.K. launch last year.

As part of the license agreement, Knight obtained the exclusive Quebec and Israeli distribution rights to Pro Bono Bio’s innovative Flexiseq™ range of pain relief products and its promising SEQuaderma™ derma-cosmetic range of products, both of which are expected to launch in Quebec within the next 12 months. In addition, Knight obtained the exclusive Canadian and Israeli rights to two earlier stage product groups: blood factor products for the treatment of Hemophiliacs, and diagnostic devices designed for the automated detection of peripheral arterial disease. [emphasis mine]

John Mayo, Chairman and CEO of Pro Bono Bio, said, “We worked night and day to find a good distribution and strategic partner to help our North American team launch our existing products and drive growth. We welcome the good Knight on our quest to deliver to Canadian and American consumers’ best-in-class, drug-free nanotechnology products that are safe, effective and of the highest quality: truly the holy grail!”

“When you donate to charity, you always receive back more than you give. I hope this truism also holds true for this Pro Bono world!” said Jonathan Ross Goodman, President and CEO of Knight. “We look forward to the late 2015 launch of Flexiseq™ and SEQuaderma™ in La Belle Province.”

The news release also provides a description of the drugs and the companies, along with a disclaimer,

About Flexiseq™

Flexiseq™ is a topically applied drug-free gel which is clinically proven to safely relieve the pain and improve the joint stiffness associated with osteoarthritis (OA). Flexiseq™ is unique – it lubricates your joints to address joint damage. Pain is relieved and joint function improved because it lubricates away the friction and associated wear and tear on a user’s joints.

About SEQuaderma™

SEQuaderma™ Dermatology Products are a unique range of active dermatology solutions specifically designed to address the symptoms and, in some cases, the causes of the targeted conditions, leading to reduced recurrence. SEQuaderma™ Dermatology Products are suitable for long term use and can be used on their own or in between drug treatments to reduce exposure to adverse events; they will not compromise any other medication and are suitable for those with multiple conditions.

About Pro Bono Bio PLC

Pro Bono Bio PLC is the world’s leading healthcare nanotechnology company offering health and lifestyle products, headquartered in London with presence in Europe, Africa and Asia and due to launch in North America. [emphasis mine]

About Knight Therapeutics Inc.

Knight Therapeutics Inc., headquartered in Montreal, Canada, is a specialty pharmaceutical company focused on acquiring or in-licensing innovative pharmaceutical products for the Canadian and select international markets. Knight’s shares trade on TSX under the symbol GUD. For more information about Knight Therapeutics Inc., please visit the Company’s web site at www.gud-knight.com or www.sedar.com.

Forward-Looking Statement [disclaimer]

This document contains forward-looking statements for the Company and its subsidiaries. These forward looking statements, by their nature, necessarily involve risks and uncertainties that could cause actual results to differ materially from those contemplated by the forward-looking statements. The Company considers the assumptions on which these forward-looking statements are based to be reasonable at the time they were prepared, but cautions the reader that these assumptions regarding future events, many of which are beyond the control of the Company and its subsidiaries, may ultimately prove to be incorrect. Factors and risks, which could cause actual results to differ materially from current expectations are discussed in the Company’s Annual Report and in the Company’s Annual Information Form for the year ended December 31, 2014. The Company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information or future events, except as required by law.

While Pro Bono Bio is headquartered in London (UK), the BloombergBusiness website lists the company as Russian,

Pro Bono Bio, an international pharmaceutical company, develops and commercializes new medicines in the Russian Federation. Its products include FLEXISEQ, a pain relieving gel containing absorbing nanostructures (Sequessomes) for the treatment of pain associated with osteoarthritis; EXOSEQ, which delivers Sequessomes to the upper dermal layers of the skin for the treatment of inflammatory conditions, such as eczema and seborrhoeic dermatitis; and ROSSOSEQ, which distributes Sequessome vesicles into lower dermal tissues in the skin to treat psoriasis and atopic eczema conditions. The company also develops blood products, CV diagnostics, anti-infectives, and biological drugs. Pro Bono Bio was …

Detailed Description

Moscow,

Russia

Founded in 2011

www.probonobio.com
Key Executives for Pro Bono Bio
Mr. John Mayo
Chief Executive Officer
Mr. Michael Earl
Chief Operating Officer
Compensation as of Fiscal Year 2014.

Pro Bono Bio Key Developments

Pro Bono Bio Appoints Jason Flowerday as CEO of North American Operations

Jun 26 15

Pro Bono Bio launched its North American operations with headquarters based in Toronto, Canada and secured USD 15 million in funding to accelerate the global launches of FLEXISEQ and SEQUADERMA as well as help fund its ambitious research and development programs that continue to place Pro Bono Bio at the forefront of nanotechnology healthcare development. Pro Bono Bio has recently appointed a North American CEO, Jason Flowerday, to build-out the North American operations and set its strategy for entering both the Canadian and US markets over the next three quarters.

Pro Bono Bio Launches its North American Operations
Jun 26 15

These are interesting developments for both Montréal (Québec) and Toronto (Ontario). As for whether or not Pro Bono Bio is Russian or British, I imagine the legal entity which is the company is Russian while the operations (headquarters as previously noted) are based in the UK.

Labeling 5nm gold nanoparticles with gold isotopes (soft core, hard shell)

There’s a lot of talk about using gold nanoparticles (and others) to deliver drugs to specific locations in the body but this research at Helmholtz Zentrum Muenchen (Munich, Germany) and the University of Marburg (Marburg, Germany) appears to be the first successful attempt at tracking how this potential delivery system might actually work. From a June 23, 2015 news item on Azonano,

Nanoparticles are the smallest particles capable of reaching virtually all parts of the body. Researchers use various approaches to test ways in which nanoparticles could be used in medicine – for instance, to deliver substances to a specific site in the body such as a tumor.

For this purpose, nanoparticles are generally coated with organic materials because their surface quality plays a key role in determining further targets in the body. If they have a water-repellent shell, nanoparticles are quickly identified by the body’s immune system and eliminated.

How gold particles wander through the body

The team of scientists headed by Dr. Wolfgang Kreyling, who is now an external scientific advisor at the Institute of Epidemiology II within the Helmholtz Zentrum Muenchen, and Prof. Wolfgang Parak from the University of Marburg, succeeded for the first time in tracking the chronological sequence of such particles in an animal model. To this end, they generated tiny 5 nm gold nanoparticles radioactively labeled with a gold isotope*. These were also covered with a polymer shell and tagged with a different radioactive isotope. According to the researchers, this was, technically speaking, a very demanding nanotechnological step.

A June 22, 2015 Helmholtz Zentrum Muenchen press release, which originated the news item, provides more detail,

After the subsequent intravenous injection of the particles, however, the team observed how the specially applied polymer shell disintegrated. “Surprisingly, the particulate gold accumulated mainly in the liver,” Dr. Kreyling recalls. “In contrast, the shell molecules reacted in a significantly different manner, distributing themselves throughout the body.” Further analyses conducted by the scientists explained the reason for this: so-called proteolytic enzymes** in certain liver cells appear to separate the particles from their shell. According to the researchers, this effect was hitherto unknown in vivo, since up to now the particle-conjugate had only been tested in cell cultures, where this effect had not been examined sufficiently thoroughly.

“Our results show that even nanoparticle-conjugates*** that appear highly stable can change their properties when deployed in the human body,” Dr. Kreyling notes, evaluating the results. “The study will thus have an influence on future medical applications as well as on the risk evaluation of nanoparticles in consumer products and in science and technology.”

* Isotopes are types of atoms which have different mass numbers but which represent the same element.

** Proteolytic enzymes split protein structures and are used, for example, to nourish or detoxify the body.

*** Conjugates are several types of molecules that are bound in one particle.

Here’s a link to and a citation for the paper,

In vivo integrity of polymer-coated gold nanoparticles by Wolfgang G. Kreyling, Abuelmagd M. Abdelmonem, Zulqurnain Ali, Frauke Alves, Marianne Geiser, Nadine Haberl, Raimo Hartmann, Stephanie Hirn, Dorleta Jimenez de Aberasturi, Karsten Kantner, Gülnaz Khadem-Saba, Jose-Maria Montenegro, Joanna Rejman, Teofilo Rojo, Idoia Ruiz de Larramendi, Roser Ufartes, Alexander Wenk, & Wolfgang J. Parak. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.111 Published online 15 June 2015

This paper is behind a paywall.