Category Archives: medicine

Like a starfish shell, facetless crystals

Made by accident, these facetless crystals could prove useful in applications for cells, medications, and more according to researchers at the University of Michigan in an Oct. 20, 2014 news item on Nanowerk,

In a design that mimics a hard-to-duplicate texture of starfish shells, University of Michigan engineers have made rounded crystals that have no facets.

“We call them nanolobes. They look like little hot air balloons that are rising from the surface,” said Olga Shalev, a doctoral student in materials science and engineering who worked on the project.

There is a video with the researcher, Olga Shalev, describing the nanolobes in more detail,

An Oct. 17, 2014 University of Michigan news release (also on EurekAlert*), which originated the news item, offers text for those who prefer to read about the science rather than receive it by video,

Both the nanolobes’ shape and the way they’re made have promising applications, the researchers say. The geometry could potentially be useful to guide light in advanced LEDs, solar cells and nonreflective surfaces. A layer might help a material repel water or dirt. And the process used to manufacture them – organic vapor jet printing – might lend itself to 3D-printing medications that absorb better into the body and make personalized dosing possible.

The nanoscale shapes are made out of boron subphthalocyanine chloride, a material often used in organic solar cells. It’s in a family of small molecular compounds that tend to make either flat films or faceted crystals with sharp edges, says Max Shtein, an associate professor of materials science and engineering, macromolecular science and engineering, chemical engineering, and art and design.

“In my years of working with these kinds of materials, I’ve never seen shapes that looked like these. They’re reminiscent of what you get from biological processes,” Shtein said. “Nature can sometimes produce crystals that are smooth, but engineers haven’t been able to do it reliably.”

Echinoderm sea creatures such as brittle stars have ordered rounded structures on their bodies that work as lenses to gather light into their rudimentary eyes. But in a lab, crystals composed of the same minerals tend either to be faceted with flat faces and sharp angles, or smooth, but lacking molecular order.

The U-M researchers made the curved crystals by accident several years ago. They’ve since traced their steps and figured out how to do it on purpose.

In 2010, Shaurjo Biswas, then a doctoral student at U-M, was making solar cells with the organic vapor jet printer. He was recalibrating the machine after switching between materials. Part of the recalibration process involves taking a close look at the fresh layers of material, of films, printed on a plate. Biswas X-rayed several films of different thicknesses to observe the crystal structure. He noticed that the boron subphthalocyanine chloride, which typically does not form ordered shapes, started to do so once the film got thicker than 600 nanometers. He made some thicker films to see what would happen.

“At first, we wondered if our apparatus was functioning properly,” Shtein said.

At 800 nanometers thick, the repeating nanolobe pattern emerged every time.

For a long while, the blobs were lab curiosities. Researchers were focused on other things. Then doctoral student Shalev got involved. She was fascinated by the structures and wanted to understand the reason for the phenomenon. She repeated the experiments in a modified apparatus that gave more control over the conditions to vary them systematically. She collaborated with physics professor Roy Clarke to gain a better understanding of the crystallization, and mechanical engineering professor Wei Lu to simulate the evolution of the surface.. She’s first author of a paper on the findings published in the current edition of Nature Communications.

“As far as we know, no other technology can do this,” Shalev said.

The organic vapor jet printing process the researchers use is a technique Shtein helped to develop when he was in graduate school. He describes it as spray painting, but with a gas rather than with a liquid. It’s cheaper and easier to do for certain applications than competing approaches that involve stencils or can only be done in a vacuum, Shtein says. He’s especially hopeful about the prospects for this technique to advance emerging 3D-printed pharmaceutical concepts.

For example, Shtein and Shalev believe this method offers a precise way to control the size and shape of the medicine particles, for easier absorption into the body. It could also allow drugs to be attached directly to other materials and it doesn’t require solvents that might introduce impurities.

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

Growth and modelling of spherical crystalline morphologies of molecular materials by O. Shalev, S. Biswas, Y. Yang, T. Eddir, W. Lu, R. Clarke,  & M. Shtein. Nature Communications 5, Article number: 5204 doi:10.1038/ncomms6204 Published 16 October 2014

This paper is behind a paywall.

* EurekAlert link added on Oct. 20, 2014 at 1035 hours PDT.

SLIPS (Slippery Liquid-Infused Porous Surfaces) technology repels blood and bacteria from medical devices

Researchers at Harvard University’s Wyss Institute for Biologically Inspired Engineering have developed a coating for medical devices that helps to address some of these devices’ most  troublesome aspects. From an Oct. 12, 2014 news item on ScienceDaily,

From joint replacements to cardiac implants and dialysis machines, medical devices enhance or save lives on a daily basis. However, any device implanted in the body or in contact with flowing blood faces two critical challenges that can threaten the life of the patient the device is meant to help: blood clotting and bacterial infection.

A team of Harvard scientists and engineers may have a solution. They developed a new surface coating for medical devices using materials already approved by the Food and Drug Administration (FDA). The coating repelled blood from more than 20 medically relevant substrates the team tested — made of plastic to glass and metal — and also suppressed biofilm formation in a study reported in Nature Biotechnology. But that’s not all.

The team implanted medical-grade tubing and catheters coated with the material in large blood vessels in pigs, and it prevented blood from clotting for at least eight hours without the use of blood thinners such as heparin. Heparin is notorious for causing potentially lethal side-effects like excessive bleeding but is often a necessary evil in medical treatments where clotting is a risk.

“Devising a way to prevent blood clotting without using anticoagulants is one of the holy grails in medicine,” said Don Ingber, M.D., Ph.D., Founding Director of Harvard’s Wyss Institute for Biologically Inspired Engineering and senior author of the study. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, as well as professor of bioengineering at Harvard School of Engineering and Applied Sciences (SEAS).

An Oct. 12, 2014 Wyss Institute news release (also on EurekAlert), which originated the news item, describes the inspiration for this work,

The idea for the coating evolved from SLIPS, a pioneering surface technology developed by coauthor Joanna Aizenberg, Ph.D., who is a Wyss Institute Core Faculty member and the Amy Smith Berylson Professor of Materials Science at Harvard SEAS. SLIPS stands for Slippery Liquid-Infused Porous Surfaces. Inspired by the slippery surface of the carnivorous pitcher plant, which enables the plant to capture insects, SLIPS repels nearly any material it contacts. The liquid layer on the surface provides a barrier to everything from ice to crude oil and blood.

“Traditional SLIPS uses porous, textured surface substrates to immobilize the liquid layer whereas medical surfaces are mostly flat and smooth – so we further adapted our approach by capitalizing on the natural roughness of chemically modified surfaces of medical devices,” said Aizenberg, who leads the Wyss Institute’s Adaptive Materials platform. “This is yet another incarnation of the highly customizable SLIPS platform that can be designed to create slippery, non-adhesive surfaces on any material.”

The Wyss team developed a super-repellent coating that can be adhered to existing, approved medical devices. In a two-step surface-coating process, they chemically attached a monolayer of perfluorocarbon, which is similar to Teflon. Then they added a layer of liquid perfluorocarbon, which is widely used in medicine for applications such as liquid ventilation for infants with breathing challenges, blood substitution, eye surgery, and more. The team calls the tethered perfluorocarbon plus the liquid layer a Tethered-Liquid Perfluorocarbon surface, or TLP for short.

In addition to working seamlessly when coated on more than 20 different medical surfaces and lasting for more than eight hours to prevent clots in a pig under relatively high blood flow rates without the use of heparin, the TLP coating achieved the following results:

  • TLP-treated medical tubing was stored for more than a year under normal temperature and humidity conditions and still prevented clot formation
  • The TLP surface remained stable under the full range of clinically relevant physiological shear stresses, or rates of blood flow seen in catheters and central lines, all the way up to dialysis machines
  • It repelled the components of blood that cause clotting (fibrin and platelets)
  • When bacteria called Pseudomonas aeruginosa were grown in TLP-coated medical tubing for more than six weeks, less than one in a billion bacteria were able to adhere. Central lines coated with TLP significantly reduce sepsis from Central-Line Mediated Bloodstream Infections (CLABSI). (Sepsis is a life-threatening blood infection caused by bacteria, and a significant risk for patients with implanted medical devices.)

Out of sheer curiosity, the researchers even tested a TLP-coated surface with a gecko – the superstar of sticking whose footpads contain many thousands of hairlike structures with tremendous adhesive strength. The gecko was unable to hold on.

“We were wonderfully surprised by how well the TLP coating worked, particularly in vivo without heparin,” said one of the co-lead authors, Anna Waterhouse, Ph.D., a Wyss Institute Postdoctoral Fellow. “Usually the blood will start to clot within an hour in the extracorporeal circuit, so our experiments really demonstrate the clinical relevance of this new coating.”

While most of the team’s demonstrations were performed on medical devices such as catheters and perfusion tubing using relatively simple setups, they say there is a lot more on the horizon.

“We feel this is just the beginning of how we might test this for use in the clinic,” said co-lead author Daniel Leslie, Ph.D., a Wyss Institute Staff Scientist, who aims to test it on more complex systems such as dialysis machines and ECMO, a machine used in the intensive care unit to help critically ill patients breathe.

I first featured SLIPS technology in a Jan. 15, 2014 post about its possible use for stain-free, self-cleaning clothing. This Wyss Institute video about the latest work featuring the use of  SLIPS technology in medical devices also describes its possible use in pipelines and airplanes,

You can find research paper with this link,

A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling by Daniel C Leslie, Anna Waterhouse, Julia B Berthet, Thomas M Valentin, Alexander L Watters, Abhishek Jain, Philseok Kim, Benjamin D Hatton, Arthur Nedder, Kathryn Donovan, Elana H Super, Caitlin Howell, Christopher P Johnson, Thy L Vu, Dana E Bolgen, Sami Rifai, Anne R Hansen, Michael Aizenberg, Michael Super, Joanna Aizenberg, & Donald E Ingber. Nature Biotechnology (2014) doi:10.1038/nbt.3020 Published online 12 October 2014

This paper is behind a paywall but there is a free preview available via ReadCube Access.

Gold nanorods and mucus

Mucus can kill. Most of us are lucky enough to produce mucus appropriate for our bodies’ needs but people who have cystic fibrosis and other kinds of lung disease suffer greatly from mucus that is too thick to pass easily through the body. An Oct. 9, 2014 Optical Society of America (OSA) news release (also on EurekAlert) ‘shines’ a light on the topic of mucus and viscosity,

Some people might consider mucus an icky bodily secretion best left wrapped in a tissue, but to a group of researchers from the University of North Carolina at Chapel Hill, snot is an endlessly fascinating subject. The team has developed a way to use gold nanoparticles and light to measure the stickiness of the slimy substance that lines our airways.  The new method could help doctors better monitor and treat lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

“People who are suffering from certain lung diseases have thickened mucus,” explained Amy Oldenburg, a physicist at the University of North Carolina at Chapel Hill whose research focuses on biomedical imaging systems. “In healthy adults, hair-like cell appendages called cilia line the airways and pull mucus out of the lungs and into the throat. But if the mucus is too viscous it can become trapped in the lungs, making breathing more difficult and also failing to remove pathogens that can cause chronic infections.”

Doctors can prescribe mucus-thinning drugs, but have no good way to monitor how the drugs affect the viscosity of mucus at various spots inside the body. This is where Oldenburg and her colleagues’ work may help.

The researchers placed coated gold nanorods on the surface of mucus samples and then tracked the rods’ diffusion into the mucus by illuminating the samples with laser light and analyzing the way the light bounced off the nanoparticles. The slower the nanorods diffused, the thicker the mucus. The team found this imaging method worked even when the mucus was sliding over a layer of cells—an important finding since mucus inside the human body is usually in motion.

“The ability to monitor how well mucus-thinning treatments are working in real-time may allow us to determine better treatments and tailor them for the individual,” said Oldenburg.

It will likely take five to 10 more years before the team’s mucus measuring method is tested on human patients, Oldenburg said. Gold is non-toxic, but for safety reasons the researchers would want to ensure that the gold nanorods would eventually be cleared from a patient’s system.

“This is a great example of interdisciplinary work in which optical scientists can meet a specific need in the clinic,” said Nozomi Nishimura, of Cornell University … . “As these types of optical technologies continue to make their way into medical practice, it will both expand the market for the technology as well as improve patient care.”

The team is also working on several lines of ongoing study that will some day help bring their monitoring device to the clinic. They are developing delivery methods for the gold nanorods, studying how their imaging system might be adapted to enter a patient’s airways, and further investigating how mucus flow properties differ throughout the body.

This work is being presented at:

The research team will present their work at The Optical Society’s (OSA) 98th Annual Meeting, Frontiers in Optics, being held Oct. 19-23 [2014] in Tucson, Arizona, USA.

Presentation FTu5F.2, “Imaging Gold Nanorod Diffusion in Mucus Using Polarization Sensitive OCT,” takes place Tuesday, Oct. 21 at 4:15 p.m. MST [Mountain Standard Time] in the Tucson Ballroom, Salon A at the JW Marriott Tucson Starr Pass Resort.

People with cystic fibrosis tend to have short lives (from the US National Library of Medicine MedLine Plus webpage on cystic fibrosis),

Most children with cystic fibrosis stay in good health until they reach adulthood. They are able to take part in most activities and attend school. Many young adults with cystic fibrosis finish college or find jobs.

Lung disease eventually worsens to the point where the person is disabled. Today, the average life span for people with CF who live to adulthood is about 37 years.

Death is most often caused by lung complications.

I hope this work proves helpful.

Nanoparticle-based radiogenetics to control brain cells

While the title for this post sounds like an opening for a zombie-themed story, this Oct. 8, 2014 news item on Nanowerk actually concerns brain research at Rockefeller University (US), Note: A link has been removed,

A proposal to develop a new way to remotely control brain cells from Sarah Stanley, a Research Associate in Rockefeller University’s Laboratory of Molecular Genetics, headed by Jeffrey M. Friedman, is among the first to receive funding from the BRAIN initiative. The project will make use of a technique called radiogenetics that combines the use of radio waves or magnetic fields with nanoparticles to turn neurons on or off.

An Oct. 7, 2014 Rockefeller University news release, which originated the news item, further describes the BRAIN initiative and the research (Note: Links have been removed),

The NIH [National Institutes of Health]  is one of four federal agencies involved in the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative. Following in the ambitious footsteps of the Human Genome Project, the BRAIN initiative seeks to create a dynamic map of the brain in action, a goal that requires the development of new technologies. The BRAIN initiative working group, which outlined the broad scope of the ambitious project, was co-chaired by Rockefeller’s Cori Bargmann, head of the Laboratory of Neural Circuits and Behavior.

Stanley’s grant, for $1.26 million over three years, is one of 58 projects to get BRAIN grants, the NIH announced. The NIH’s plan for its part of this national project, which has been pitched as “America’s next moonshot,” calls for $4.5 billion in federal funds over 12 years.

The technology Stanley is developing would enable researchers to manipulate the activity of neurons, as well as other cell types, in freely moving animals in order to better understand what these cells do. Other techniques for controlling selected groups of neurons exist, but her new nanoparticle-based technique has a unique combination of features that may enable new types of experimentation. For instance, it would allow researchers to rapidly activate or silence neurons within a small area of the brain or dispersed across a larger region, including those in difficult-to-access locations. Stanley also plans to explore the potential this method has for use treating patients.

“Francis Collins, director of the NIH, has discussed the need for studying the circuitry of the brain, which is formed by interconnected neurons. Our remote-control technology may provide a tool with which researchers can ask new questions about the roles of complex circuits in regulating behavior,” Stanley says.

Here’s an image that Rockefeller University has used to illustrate the concept of radio-controlled brain cells,

 

BRAIN control: The new technology uses radio waves to activate or silence cells remotely. The bright spots above represent cells with increased calcium after treatment with radio waves, a change that would allow neurons to fire. [downloaded from: http://newswire.rockefeller.edu/2014/10/07/rockefeller-neurobiology-lab-is-awarded-first-round-brain-initiative-grant/]

BRAIN control: The new technology uses radio waves to activate or silence cells remotely. The bright spots above represent cells with increased calcium after treatment with radio waves, a change that would allow neurons to fire. [downloaded from: http://newswire.rockefeller.edu/2014/10/07/rockefeller-neurobiology-lab-is-awarded-first-round-brain-initiative-grant/]

You can find out more about the US BRAIN initiative here.

Nanotechnology for better treatment of eye conditions and a perspective on superhuman sight

There are three ‘eye’-related items in this piece, two of them concerning animal eyes and one concerning a camera-eye or the possibility of superhuman sight.

Earlier this week researchers at the University of Reading (UK) announced they have achieved a better understanding of how nanoparticles might be able to bypass some of the eye’s natural barriers in the hopes of making eye drops more effective in an Oct. 7, 2014 news item on Nanowerk,

Sufferers of eye disorders have new hope after researchers at the University of Reading discovered a potential way of making eye drops more effective.

Typically less than 5% of the medicine dose applied as drops actually penetrates the eye – the majority of the dose will be washed off the cornea by tear fluid and lost.

The team, led by Professor Vitaliy Khutoryanskiy, has developed novel nanoparticles that could attach to the cornea and resist the wash out effect for an extended period of time. If these nanoparticles are loaded with a drug, their longer attachment to the cornea will ensure more medicine penetrates the eye and improves drop treatment.

An Oct. 6, 2014 University of Reading press release, which originated the news item, provides more information about the hoped for impact of this work while providing few details about the research (Note: A link has been removed),

The research could also pave the way for new treatments of currently incurable eye-disorders such as Age-related Macular Degeneration (AMD) – the leading cause of visual impairment with around 500,000 sufferers in the UK.

There is currently no cure for this condition but experts believe the progression of AMD could be slowed considerably using injections of medicines into the eye. However, eye-drops with drug-loaded nanoparticles could be a potentially more effective and desirable course of treatment.

Professor Vitaliy Khutoryanskiy, from the University of Reading’s School of Pharmacy, said: “Treating eye disorders is a challenging task. Our corneas allow us to see and serve as a barrier that protects our eyes from microbial and chemical intervention. Unfortunately this barrier hinders the effectiveness of eye drops. Many medicines administered to the eye are inefficient as they often cannot penetrate the cornea barrier. Only the very small molecules in eye drops can penetrate healthy cornea.

“Many recent breakthroughs to treat eye conditions involve the use of drugs incorporated into nano-containers; their role being to promote drug penetration into the eye.  However the factors affecting this penetration remain poorly understood. Our research also showed that penetration of small drug molecules could be improved by adding enhancers such as cyclodextrins. This means eye drops have the potential to be a more effective, and a more comfortable, future treatment for disorders such as AMD.”

The finding is one of a number of important discoveries highlighted in a paper published today in the journal Molecular Pharmaceutics. The researchers revealed fascinating insights into how the structure of the cornea prevents various small and large molecules, as well as nanoparticles, from entering into the eye. They also examined the effects any damage to the eye would have in allowing these materials to enter the body.

Professor Khutoryanskiy continued: “There is increasing concern about the safety of environmental contaminants, pollutants and nanoparticles and their potential impacts on human health. We tested nanoparticles whose sizes ranged between 21 – 69 nm, similar to the size of viruses such as polio, or similar to airborn particles originating from building industry and found that they could not penetrate healthy and intact cornea irrespective of their chemical nature.

“However if the top layer of the cornea is damaged, either after surgical operation or accidentally, then the eye’s natural defence may be compromised and it becomes susceptible to viral attack which could result in eye infections.

“The results show that our eyes are well-equipped to defend us against potential airborne threats that exist in a fast-developing industrialised world. However we need to be aware of the potential complications that may arise if the cornea is damaged, and not treated quickly and effectively.”

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

On the Barrier Properties of the Cornea: A Microscopy Study of the Penetration of Fluorescently Labeled Nanoparticles, Polymers, and Sodium Fluorescein by Ellina A. Mun, Peter W. J. Morrison, Adrian C. Williams, and Vitaliy V. Khutoryanskiy. Mol. Pharmaceutics, 2014, 11 (10), pp 3556–3564 DOI: 10.1021/mp500332m Publication Date (Web): August 28, 2014

Copyright © 2014 American Chemical Society

There’s a little more information to be had in the paper’s abstract, which is, as these things go, is relatively accessible,

[downloaded from http://pubs.acs.org/doi/abs/10.1021/mp500332m]

[downloaded from http://pubs.acs.org/doi/abs/10.1021/mp500332m]

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase.

The paper is behind a paywall. No mention is made in the abstract or in the press release as to how the bovine (ox, cow, or buffalo) eyes were obtained but I gather these body parts are often harvested from animals that have been previously slaughtered for food.

This next item also concerns research about eye drops but this time the work comes from the University of Waterloo (Ontario, Canada). From an Oct. 8, 2014 news item on Azonano,

For the millions of sufferers of dry eye syndrome, their only recourse to easing the painful condition is to use drug-laced eye drops three times a day. Now, researchers from the University of Waterloo have developed a topical solution containing nanoparticles that will combat dry eye syndrome with only one application a week.

An Oct. 8, 2014 University of Waterloo news release (also on EurekAlert), which originated the news item, describes the results of the work without providing much detail about the nanoparticles used to deliver the treatment via eye drops,

The eye drops progressively deliver the right amount of drug-infused nanoparticles to the surface of the eyeball over a period of five days before the body absorbs them.  One weekly dose replaces 15 or more to treat the pain and irritation of dry eyes.

The nanoparticles, about 1/1000th the width of a human hair, stick harmlessly to the eye’s surface and use only five per cent of the drug normally required.

“You can’t tell the difference between these nanoparticle eye drops and water,” said Shengyan (Sandy) Liu, a PhD candidate at Waterloo’s Faculty of Engineering, who led the team of researchers from the Department of Chemical Engineering and the Centre for Contact Lens Research. “There’s no irritation to the eye.”

Dry eye syndrome is a more common ailment for people over the age of 50 and may eventually lead to eye damage. More than six per cent of people in the U.S. have it. Currently, patients must frequently apply the medicine three times a day because of the eye’s ability to self-cleanse—a process that washes away 95 per cent of the drug.

“I knew that if we focused on infusing biocompatible nanoparticles with Cyclosporine A, the drug in the eye drops, and make them stick to the eyeball without irritation for longer periods of time, it would also save patients time and reduce the possibility of toxic exposure due to excessive use of eye drops,” said Liu.

The research team is now focusing on preparing the nanoparticle eye drops for clinical trials with the hope that this nanoparticle therapy could reach the shelves of drugstores within five years.

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

Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentallyinduced dry eye syndrome by Shengyan Liu, Chu Ning Chang, Mohit S. Verma, Denise Hileeto, Alex Muntz, Ulrike Stahl, Jill Woods, Lyndon W. Jones, and Frank X. Gu. Nano Research (October 2014) DOI: 10.1007/s12274-014-0547-3

This paper is behind a paywall. There is a partial preview available for free. As per the paper’s abstract, research was performed on healthy rabbit eyes.

The last ‘sight’ item I’m featuring here comes from the Massachusetts Institute of Technology (MIT) and does not appear to have been occasioned by the publication of a research paper or some other event. From an Oct. 7, 2014 news item on Azonano,

All through his childhood, Ramesh Raskar wished fervently for eyes in the back of his head. “I had the notion that the world did not exist if I wasn’t looking at it, so I would constantly turn around to see if it was there behind me.” Although this head-spinning habit faded during his teen years, Raskar never lost the desire to possess the widest possible field of vision.

Today, as director of the Camera Culture research group and associate professor of Media Arts and Sciences at the MIT Media Lab, Raskar is realizing his childhood fantasy, and then some. His inventions include a nanocamera that operates at the speed of light and do-it-yourself tools for medical imaging. His scientific mission? “I want to create not just a new kind of vision, but superhuman vision,” Raskar says.

An Oct. 6, 2014 MIT news release, which originated the news item, provides more information about Raskar and his research,

He avoids research projects launched with a goal in mind, “because then you only come up with the same solutions as everyone else.” Discoveries tend to cascade from one area into another. For instance, Raskar’s novel computational methods for reducing motion blur in photography suggested new techniques for analyzing how light propagates. “We do matchmaking; what we do here can be used over there,” says Raskar.

Inspired by the famous microflash photograph of a bullet piercing an apple, created in 1964 by MIT professor and inventor Harold “Doc” Edgerton, Raskar realized, “I can do Edgerton millions of times faster.” This led to one of the Camera Culture group’s breakthrough inventions, femtophotography, a process for recording light in flight.

Manipulating photons into a packet resembling Edgerton’s bullet, Raskar and his team were able to “shoot” ultrashort laser pulses through a Coke bottle. Using a special camera to capture the action of these pulses at half a trillion frames per second with two-trillionths of a second exposure times, they captured moving images of light, complete with wave-like shadows lapping at the exterior of the bottle.

Femtophotography opened up additional avenues of inquiry, as Raskar pondered what other features of the world superfast imaging processes might reveal. He was particularly intrigued by scattered light, the kind in evidence when fog creates the visual equivalent of “noise.”

In one experiment, Raskar’s team concealed an object behind a wall, out of camera view. By firing super-short laser bursts onto a surface nearby, and taking millions of exposures of light bouncing like a pinball around the scene, the group rendered a picture of the hidden object. They had effectively created a camera that peers around corners, an invention that might someday help emergency responders safely investigate a dangerous environment.

Raskar’s objective of “making the invisible visible” extends as well to the human body. The Camera Culture group has developed a technique for taking pictures of the eye using cellphone attachments, spawning inexpensive, patient-managed vision and disease diagnostics. Conventional photography has evolved from time-consuming film development to instantaneous digital snaps, and Raskar believes “the same thing will happen to medical imaging.” His research group intends “to break all the rules and be at the forefront. I think we’ll get there in the next few years,” he says.

Ultimately, Raskar predicts, imaging will serve as a catalyst of transformation in all dimensions of human life — change that can’t come soon enough for him. “I hate ordinary cameras,” he says. “They record only what I see. I want a camera that gives me a superhuman perspective.”

Following the link to the MIT news release will lead you to more information about Raskar and his work. You can also see and hear Raskar talk about his femtophotography in a 2012 TEDGlobal talk here.

Murdoch University (Australia) encourages* bone formation in sheep

It’s time to finally publish this which has been languishing in drafts folder: from a Sept. 16, 2014 news item on Nanowerk (Note: A link has been removed),

Murdoch University [Australia] nanotechnology researchers have successfully engineered synthetic materials which encouraged bone formation in sheep (“The synthesis, characterisation and in vivo study of a bioceramic for potential tissue regeneration applications”).

The advancement means the successful use of synthetic materials in bone grafts for human patients is a step closer. The material could also have potential future applications in fracture repair and reconstructive surgery.

A Sept. 16, 2014 Murdoch University news release, which originated the news item, notes

Currently the patient’s own bone, donated bone or artificial materials are used for bone grafts but limitations with all these options have prompted researchers to investigate how synthetic materials can be enhanced.

Dr Eddy Poinern and his team from the Murdoch Applied Nanotechnology Research Group worked with powdered forms of the bio ceramic hydroxyapatite (HAP) to form pellets with a sponge-like structure which were then successfully implanted behind the shoulders of four sheep by collaborators from the School of Veterinary and Life Sciences at Murdoch University.

HAP is already being used in a number of biomedical applications such as bone augmentation in dentistry because of its similarity to the inorganic mineral component of human bone. But treatments of HAP so that it can be successfully used in a bone graft have yet to be developed because of the complexities involved with compatibility and HAP’s load bearing limitations.

The news release goes on to provide a few technical details,

Dr Poinern and his team prepared pellets with varying density and porosity using a variety of chemical methods including sintering, ultrasound and microwaves. Four pellets were implanted into muscles in each of the sheep, later demonstrating good bio-compatibility, including mixed cell colonisation after four weeks and even new bone formation 12 weeks after the surgery.

“Using synthetic materials in this way is difficult and complicated because they need to be engineered to be porous and to replicate the various physical, chemical and mechanical properties found in natural bone tissue,” explained Dr Poinern.

“They also need to be non-toxic and have a degradation rate which will allow for cells from the host to steadily recolonize the area and permit the formation of blood vessels necessary for the delivery of nutrients to the forming bone tissues.

“We already knew that synthetic HAP was a good material to study for possible use in bone-related medicine, but we needed to find out if the pellets we’d engineered were bio-compatible.

“Our results were very positive – our pellets acted as a scaffold for the growth of bone material, made possible because of its porous properties allowing cells to infiltrate.

“The pellets were also very cost effective to make.”

Although the study was small scale and originally intended to test the bio-compatibility of the HAP pellets, the bone growth was beyond what the interdisciplinary team expected.

Associate Professor Martin Cake, who surgically implanted the pellets into the sheep, described the results as “stunning” and said they boded well for the use of engineered HAP in bone implants.

“This material begins as a powder that can be theoretically moulded to any shape, or perhaps one day even 3D printed, then sintered to harden it,” he said.

Dr Poinern said he was hoping to improve and match the physical and mechanical properties of the pellets with those of natural bone tissue in a new study.

“Once these properties have been achieved, further implantation studies will be carried out to establish the feasibility of using this scaffold for bone grafts,” he said.

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

The synthesis, characterisation and in vivo study of a bioceramic for potential tissue regeneration applications by Gérrard Eddy Jai Poinern, Ravi Krishna Brundavanam, Xuan Thi Le, Philip K. Nicholls, Martin A. Cake, & Derek Fawcett. Scientific Reports 4, Article number: 6235 doi:10.1038/srep06235 Published 29 August 2014

This paper is open access.

This news release included information of a type I haven’t previously seen included,

The implantation study was carried out in non pregnant Merino ewes with the approval of Murdoch University’s Animal Ethics Committee and all experiments were conducted in accordance with the Australian National Health and Medical Research Council’s (NHMRC) Code of Practice for the care and use of animals for scientific purposes.

In accordance with the ethical principles of the Code, the sheep were simultaneously used in an unrelated trial involving surgery of the stifle joints.

After the pellets were removed, the sheep were humanely euthanased.

I’m glad to see the information and hope more research groups follow suit.

One final note, Murdoch University, Eddy Poinern, and Dereck Fawcett have been mentioned here before in an Aug. 1, 2014 posting about ‘green’ chemistry involving eucalyptus leaves, and gold nanoparticles.

* ‘encourage’ corrected to ‘encourages’ on Oct. 7, 2014 at 1315 hours PDT.

‘Glow in the dark’, paint-on bandage heals

Somewhat unexpectedly (to me), this research about a ‘smart’ paint-on bandage is being published by The Optical Society of America (OSA). Here’s more about the work from an Oct. 1, 2014 news item on Nanowerk,

Inspired by a desire to help wounded soldiers, an international, multidisciplinary team of researchers led by Assistant Professor Conor L. Evans at the Wellman Center for Photomedicine of Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) has created a paint-on, see-through, “smart” bandage that glows to indicate a wound’s tissue oxygenation concentration. Because oxygen plays a critical role in healing, mapping these levels in severe wounds and burns can help to significantly improve the success of surgeries to restore limbs and physical functions.

An Oct. 1, 2014 OSA news release (also on EurekAlert), which originated the news item, describes the interest in oxygenation in more detail,

“Information about tissue oxygenation is clinically relevant but is often inaccessible due to a lack of accurate or noninvasive measurements,” explained lead author Zongxi Li, an HMS research fellow on Evans’ team.

Now, the “smart” bandage developed by the team provides direct, noninvasive measurement of tissue oxygenation by combining three simple, compact and inexpensive components: a bright sensor molecule with a long phosphorescence lifetime and appropriate dynamic range; a bandage material compatible with the sensor molecule that conforms to the skin’s surface to form an airtight seal; and an imaging device capable of capturing the oxygen-dependent signals from the bandage with high signal-to-noise ratio.

This work is part of the team’s long-term program “to develop a Sensing, Monitoring And Release of Therapeutics (SMART) bandage for improved care of patients with acute or chronic wounds,” says Evans …

The news release goes on to briefly explain the technology,

For starters, the bandage’s not-so-secret key ingredient is phosphors—molecules that absorb light and then emit it via a process known as phosphorescence.

Phosphorescence is encountered by many on a daily basis—ranging from glow-in-the-dark dials on watches to t-shirt lettering. “How brightly our phosphorescent molecules emit light depends on how much oxygen is present,” said Li. “As the concentration of oxygen is reduced, the phosphors glow both longer and more brightly.” To make the bandage simple to interpret, the team also incorporated a green oxygen-insensitive reference dye, so that changes in tissue oxygenation are displayed as a green-to-red colormap.

The bandage is applied by “painting” it onto the skin’s surface as a viscous liquid, which dries to a solid thin film within a minute. Once the first layer has dried, a transparent barrier layer is then applied atop it to protect the film and slow the rate of oxygen exchange between the bandage and room air—making the bandage sensitive to the oxygen within tissue.

The final piece involves a camera-based readout device, which performs two functions: it provides a burst of excitation light that triggers the emission of the phosphors inside the bandage, and then it records the phosphors’ emission. “Depending on the camera’s configuration, we can measure either the brightness or color of the emitted light across the bandage or the change in brightness over time,” Li said. “Both of these signals can be used to create an oxygenation map.”  The emitted light from the bandage is bright enough that it can be acquired using a regular camera or smartphone—opening the possibility to a portable, field-ready device.

There are some immediate applications, as well as, plans for research that will yield applications (from the news release),

Immediate applications for the oxygen-sensing bandage include monitoring patients with a risk of developing ischemic (restricted blood supply) conditions, postoperative monitoring of skin grafts or flaps, and burn-depth determination as a guide for surgical debridement—the removal of dead or damaged tissue from the body.

“The need for a reliable, accurate and easy-to-use method of rapid assessment of blood flow to the skin for patients remains a clinical necessity,” said co-author Samuel Lin, an HMS associate professor of surgery at Beth Israel Deaconess Medical Center. “Plastic surgeons continuously monitor the state of blood flow to the skin, so the liquid-bandage oxygenation sensor is an exciting step toward improving patient care within the realm of vascular blood flow examination of the skin.”

What’s the next step for the bandage? “We’re developing brighter sensor molecules to improve the bandage’s oxygen sensing efficiency,” said Emmanuel Roussakis, another research fellow in Evans’ laboratory and co-author, who is leading the sensor development effort.  The team’s laboratory research will also focus on expanding the sensing capability of the bandage to other treatment-related parameters—such as pH, bacterial load, oxidative states and specific disease markers—and incorporating an on-demand drug release capacity.

“In the future, our goal for the bandage is to incorporate therapeutic release capabilities that allow for on-demand drug administration at a desired location,” says Evans. “It allows for the visual assessment of the wound bed, so treatment-related wound parameters are readily accessible without the need for bandage removal—preventing unnecessary wound disruption and reducing the chance for bacterial infection.”

Should you be interested, the researchers are looking for industry partners,

Beyond the lab, the team’s aim is to move this technology from the bench to the bedside, so they are actively searching for industry partners. They acknowledge research support from the Military Medical Photonics Program from the U.S. Department of Defense, and National Institutes of Health.

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

Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage by Zongxi Li, Emmanuel Roussakis, Pieter G. L. Koolen, Ahmed M. S. Ibrahim, Kuylhee Kim, Lloyd F. Rose, Jesse Wu, Alexander J. Nichols, Yunjung Baek, Reginald Birngruber, Gabriela Apiou-Sbirlea, Robina Matyal, Thomas Huang, Rodney Chan, Samuel J. Lin, and Conor L. Evans. Biomedical Optics Express, Vol. 5, Issue 11, pp. 3748-3764 (2014) http://dx.doi.org/10.1364/BOE.5.003748

This article is open access.

The researcher’s have provided an illustration of the bandage,

Caption: The transparent liquid bandage displays a quantitative, oxygenation-sensitive colormap that can be easily acquired using a simple camera or smartphone. Credit: Li/Wellman Center for Photomedicine.

Caption: The transparent liquid bandage displays a quantitative, oxygenation-sensitive colormap that can be easily acquired using a simple camera or smartphone. Credit: Li/Wellman Center for Photomedicine.

Wonders of curcumin: wound healing; wonders of aromatic-turmerone: stem cells

Both curcumin and turmerone are constituents of turmeric which has been long lauded for its healing properties. Michael Berger has written a Nanowerk Spotlight article featuring curcumin and some recent work on burn wound healing. Meanwhile, a ScienceDaily news item details information about a team of researchers focused on tumerone as a means for regenerating brain stem cells.

Curcumin and burn wounds

In a Sept. 22, 2014 Nanowerk Spotlight article Michael Berger sums up the curcumin research effort (referencing some of this previous articles on the topic) in light of a new research paper about burn wound healing (Note: Links have been removed),

Despite significant progress in medical treatments of severe burn wounds, infection and subsequent sepsis persist as frequent causes of morbidity and mortality for burn victims. This is due not only to the extensive compromise of the protective barrier against microbial invasion, but also as a result of growing pathogen resistance to therapeutic options.

… Dr Adam Friedman, Assistant Professor of Dermatology and Director of Dermatologic research at the Montefiore-Albert Einstein College of Medicine, tells Nanowerk. “For me, this gap fuels innovation, serving as the inspiration for my research with broad-spectrum, multi-mechanistic antimicrobial nanomaterials.”

In new work, Friedman and a team of researchers from Albert Einstein College of Medicine and Oregon State University have explored the use of curcumin nanoparticles for the treatment of infected burn wounds, an application that resulted in reduced bacterial load and enhancing wound healing.

It certainly seems promising as per the article abstract,

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent by Aimee E. Krausz, Brandon L. Adler, Vitor Cabral, Mahantesh Navati, Jessica Doerner, Rabab Charafeddine, Dinesh Chandra, Hongying Liang, Leslie Gunther, Alicea Clendaniel, Stacey Harper, Joel M. Friedman, Joshua D. Nosanchuk, & Adam J. Friedman. Nanomedicine: Nanotechnology, Biology and Medicine (article in press) published online 19 September 2014.http://www.nanomedjournal.com/article/S1549-9634%2814%2900527-9/abstract Uncorrected Proof

Burn wounds are often complicated by bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat burn wound infection are limited by toxicity, incomplete microbial coverage, inadequate penetration, and rising resistance. Curcumin is a naturally derived substance with innate antimicrobial and wound healing properties. Acting by multiple mechanisms, curcumin is less likely than current antibiotics to select for resistant bacteria.

Curcumin’s poor aqueous solubility and rapid degradation profile hinder usage; nanoparticle encapsulation overcomes this pitfall and enables extended topical delivery of curcumin.

In this study, we synthesized and characterized curcumin nanoparticles (curc-np), which inhibited in vitro growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in dose-dependent fashion, and inhibited MRSA growth and enhanced wound healing in an in vivo murine wound model. Curc-np may represent a novel topical antimicrobial and wound healing adjuvant for infected burn wounds and other cutaneous injuries.

Two things: This paper is behind a paywall and note the use of the term ‘in vivo’ which means they have tested on animals such as rats and mice for example, but not humans. Nonetheless, it seems a promising avenue for further exploration.

Interestingly, there was an attempt in 1995 to patent turmeric for use in wound healing as per my Dec. 26, 2011 posting which featured then current research on turmeric,

There has already been one court case regarding a curcumin patent,

Recently, turmeric came into the global limelight when the controversial patent “Use of Turmeric in Wound Healing” was awarded, in 1995, to the University of Mississippi Medical Center, USA. Indian Council of Scientific and Industrial Research (CSIR) aggressively contested this award of the patent. It was argued by them that turmeric has been an integral part of the traditional Indian medicinal system over several centuries, and therefore, is deemed to be ‘prior art’, hence is in the public domain. Subsequently, after protracted technical/legal battle USPTO decreed that turmeric is an Indian discovery and revoked the patent.

One last bit about curcumin, my April 22, 2014 posting featured work in Iran using curcumin for cancer-healing.

Tumerone

This excerpt from a Sept. 25, 2014, news item in ScienceDaily represents the first time that tumerone has been mentioned here,

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer’s disease.

A Sept. 25, 2014 news release on EurekAlert provides more information,

The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone’s impact on the brain’s capacity to self-repair was unknown.

Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.

To test the effects of ar-turmerone on NSC in vivo, the researchers injected adult rats with ar-turmerone. Using PET imaging and a tracer to detect proliferating cells, they found that the subventricular zone (SVZ) was wider, and the hippocampus expanded, in the brains of rats injected with ar-turmerone than in control animals. The SVZ and hippocampus are the two sites in adult mammalian brains where neurogenesis, the growth of neurons, is known to occur.

Lead author of the study, Adele Rueger, said: “While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal.”

Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties

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

Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo by Joerg Hucklenbroich, Rebecca Klein, Bernd Neumaier, Rudolf Graf, Gereon Rudolf Fink, Michael Schroeter, and Maria Adele Rueger. Stem Cell Research & Therapy 2014, 5:100  doi:10.1186/scrt500

This is an open access paper.

Treatment for patients infected with the ebola virus (a response to crisis in West African countries)

I’ve not actively kept up with the situation in the West African countries suffering an outbreak of the ebola virus other than to note that it is ongoing. My Aug. 15, 2014 post provides a snapshot of the situation and various new treatments, including one based on tobacco, which could be helpful but appeared not to have been tested and/or deployed. There was a lot of secrecy (especially from Medicago, a Canadian company) regarding the whole matter of treatments and vaccines.

There seem to have been some new developments on the treatment side, involving yet another Canadian company, Tekmira, according to a Sept. 23, 2013 news item on Azonano,

Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, today announced that the FDA [US Food and Drug Administration] has authorized Tekmira to provide TKM-Ebola for treatment under expanded access protocols to subjects with confirmed or suspected Ebola virus infections.

A Sept. 22, 2014 Tekmira news release, which originated the news item, expands on the topic of regulatory issues associated with bringing this treatment to the areas suffering the outbreak,

“Tekmira is reporting that an appropriate regulatory and clinical framework is now in place to allow the use of TKM-Ebola in patients. We have worked with the FDA and Health Canada to establish this framework and a treatment protocol allowing us to do what we can to help these patients,” said Dr. Mark J. Murray Tekmira’s President and CEO.

“We have insisted on acting responsibly in the interest of patients and our stakeholders,” added Dr. Murray. “Today we are reporting that, working closely with regulators in the United States and Canada, we have established a framework for TKM-Ebola use in multiple patients. In the US, the FDA has granted expanded access use of TKM-Ebola under our Investigational New Drug application (IND) and Health Canada has established a similar framework, both of which allow the use of our investigational therapeutic in more patients.”

“We have already responded to requests for the use of our investigational agent in several patients under emergency protocols, in an effort to help these patients, a goal we share with the FDA and Health Canada. TKM-Ebola has been administered to a number of patients and the repeat infusions have been well tolerated. However, it must be kept in mind that any uses of the product under expanded access, does not constitute controlled clinical trials. These patients may be infected with a strain of Ebola virus which has emerged subsequent to the strain that our product is directed against, and physicians treating these patients may use more than one therapeutic intervention in an effort to achieve the best outcome,” said Dr. Murray. “Our TKM-Ebola drug supplies are limited, but we will continue to help where we can, as we continue to focus on the other important objectives we have to advance therapies to meet the unmet needs of patients.”

TKM-Ebola is an investigational therapeutic, being developed under an FDA approved IND, which is currently the subject of a partial clinical hold under which the FDA has allowed the potential use of TKM-Ebola in individuals with a confirmed or suspected Ebola virus infection.

About FDA Expanded Access Program

Expanded access is the use of an investigational drug outside of a clinical trial to treat a patient, with a serious or immediately life-threatening disease or condition, who has no comparable or satisfactory alternative treatment options. FDA regulations allow access to investigational drugs for treatment purposes on a case-by-case basis for an individual patient, or for intermediate-size groups of patients with similar treatment needs who otherwise do not qualify to participate in a clinical trial. (Source: www.fda.com)

About TKM-Ebola, an Anti-Ebola Virus RNAi Therapeutic

TKM-Ebola, an anti-Ebola virus RNAi therapeutic, is being developed under a $140 million contract with the U.S. Department of Defense’s Medical Countermeasure Systems BioDefense Therapeutics (MCS-BDTX) Joint Product Management Office. Earlier preclinical studies were published in the medical journal The Lancet and demonstrated that when siRNA targeting the Ebola virus and delivered by Tekmira’s LNP [Lipid Nanoparticle] technology were used to treat previously infected non-human primates, the result was 100 percent protection from an otherwise lethal dose of Zaire Ebola virus (Geisbert et al., The Lancet, Vol. 375, May 29, 2010). In March 2014, Tekmira was granted a Fast Track designation from the U.S. Food and Drug Administration for the development of TKM-Ebola.

About Joint Project Manager Medical Countermeasure Systems (JPM-MCS)

This work is being conducted under contract with the U.S. Department of Defense Joint Project Manager Medical Countermeasure Systems (JPM-MCS). JPM-MCS, a component of the Joint Program Executive Office for Chemical and Biological Defense, aims to provide U.S. military forces and the nation with safe, effective, and innovative medical solutions to counter chemical, biological, radiological, and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance biodefense response capability. For more information, visit www.jpeocbd.osd.mil.

About Tekmira

Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle (LNP) delivery technology to pharmaceutical partners. Tekmira has been working in the field of nucleic acid delivery for over a decade and has broad intellectual property covering LNPs. Further information about Tekmira can be found at www.tekmira.com. Tekmira is based in Vancouver, B.C. Canada.

Forward-Looking Statements and Information

This news release contains “forward-looking statements” or “forward-looking information” within the meaning of applicable securities laws (collectively, “forward-looking statements”). Forward-looking statements in this news release include statements about Tekmira’s strategy, future operations, clinical trials, prospects and the plans of management; an appropriate regulatory and clinical  framework for emergency use of TKM-Ebola in subjects with confirmed or suspected Ebola infections; FDA grant of expanded access use of TKM-Ebola under Tekmira’s IND; Health Canada’s establishment of a similar framework for TKM-Ebola; Tekmira’s response to requests for the use of TKM-Ebola in several patients under emergency protocols and the results thereon; the current supply of TKM-Ebola drug; the partial clinical hold on the TKM-Ebola IND by the FDA (enabling the potential use of TKM-Ebola in individuals with a confirmed or suspected Ebola virus infection); the quantum value of the contract with the JPM-MCS; and Fast Track designation from the FDA for the development of TKM-Ebola.

With respect to the forward-looking statements contained in this news release, Tekmira has made numerous assumptions regarding, among other things, the clinical framework for emergency use of TKM-Ebola. While Tekmira considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies.

Additionally, there are known and unknown risk factors which could cause Tekmira’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained herein. Known risk factors include, among others: TKM-Ebola may not prove to be effective in the treatment of Ebola infection under the emergency use framework, or at all; any uses of TKM-Ebola under emergency INDs are not controlled trails, and TKM-Ebola may be used on Ebola strains that have diverged from the strain to which TKM-Ebola is directed, and physicians treating patients may use more than one therapeutic intervention in addition to TKM-Ebola; the current supply of TKM-Ebola is limited, and Tekmira may not be able to respond to future requests for help in the current Ebola outbreak; the FDA may not remove the partial clinical hold on the TKM-Ebola IND; the FDA may refuse to approve Tekmira’s products, or place restrictions on Tekmira’s ability to commercialize its products; anticipated pre-clinical and clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the tested drug candidate; and Tekmira may not receive the necessary regulatory approvals for the clinical development of Tekmira’s products.

A more complete discussion of the risks and uncertainties facing Tekmira appears in Tekmira’s Annual Report on Form 10-K and Tekmira’s continuous disclosure filings, which are available at www.sedar.com or www.sec.gov. All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Tekmira disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law.

In the midst of all those ‘cover your rear end’ statements to investors, it’s easy to miss the fact that people are actually being treated and the results are promising, if not guaranteed,

Tekmira has distributed a Sept. 23, 2014 news release touting its membership in a new consortium, which suggests that in parallel with offering treatment, human clinical trials will  also be conducted,

Tekmira Pharmaceuticals Corporation (Nasdaq:TKMR) (TSX:TKM), a leading developer of RNA interference (RNAi) therapeutics, today reported that it is collaborating with an international consortium to provide an RNAi based investigational therapeutic for expedited clinical studies in West Africa.

Led by Dr. Peter Horby of the Centre for Tropical Medicine and Global Health at the University of Oxford and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), the consortium includes representatives from the World Health Organization (WHO), US Centers for Disease Control, Médecins Sans Frontières – Doctors without Borders (MSF), ISARIC, and Fondation Mérieux, among others.

The Wellcome Trust has announced it has awarded £3.2 million to the consortium to fund this initiative. The award will include funds for the manufacture of investigational therapeutics as well as the establishment of an operational clinical trials platform in two or more Ebola Virus Disease (EVD) treatment centers in West Africa. RNAi has been prioritized as an investigational therapeutic and may be selected for clinical trials at these centers.

The objective of the clinical trials is to assess the efficacy and safety of promising therapeutics and vaccines, reliably and safely, in patients with EVD by adopting strict protocols that comply with international standards.  It is hoped this initiative will permit the adoption of safe and effective interventions rapidly.

The genetic sequence of the Ebola virus variant responsible for the ongoing outbreak in West Africa is now available. Under this program, Tekmira will produce an RNAi based product specifically targeting the viral variant responsible for this outbreak.  The ability to rapidly and accurately match the evolving genetic sequences of emerging infectious agents is one of the powerful features of RNAi therapeutics.

“We commend the Wellcome Trust for their leadership in providing the necessary funds to launch and expedite this ground breaking initiative. We are gratified that RNAi has been prioritized as a potential investigational therapeutic to assist in the ongoing public health and humanitarian crisis in Africa,” said Dr. Murray, Tekmira’s President and CEO.

“We are an active collaborator in this consortium and through our ongoing dialogue with the WHO, NGOs and governments in various countries; we have been discussing the creation of appropriate clinical and regulatory frameworks for the potential use of investigational therapeutics in Africa. This initiative goes a long way towards achieving this aim.  Many complex decisions remain to fully implement this unique clinical trial platform.  At this time, there can be no assurances that our product will be selected by the consortium for clinical trials in Africa,” said Dr. Murray.

About Wellcome Trust

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. For more information, visit www.wellcome.ac.uk

I’m glad they’re being careful while giving people treatment, i. e., trying to do something rather than waiting to conduct human clinical trials as has sometimes been the case in the past. This business of running the trials almost parallel to offering treatment suggests an agility not often associated with the international health care community.

ETA Sept. 23 2014 1200 hours PDT: For more information about the status of the Ebola outbreak read Tara Smith’s Sept. 22, 2014 article Slate titled, Here’s Where We Stand With Ebola; Even experienced international disaster responders are shocked at how bad it’s gotten (Note: Links have been removed).

Now, terms like “exponential spread” are being thrown around as the epidemic continues to expand more and more rapidly. Just last week, an increase of 700 new cases was reported, and the case count is now doubling in size approximately every three weeks.

A Doctors Without Borders worker in Monrovia, Liberia, named Jackson Naimah describes the situation in his home country, noting that patients are literally dying at the front door of his treatment center because it lacks patient beds and assistance; the sufferers are left to die a “horrible, undignified death” and potentially infect others as they do so: …

… Health care workers who are treating the sick are dying because they also lack basic protective equipment, or because they have been so overwhelmed by taking care of the ill and dying that they begin to make potentially fatal errors. They have gone on strike in Liberia because they are not being adequately protected or even paid for their risky service.

Fear and misinformation are as deadly as the virus itself. Eight Ebola workers were recently murdered in Guinea, in the area where the virus first came to the world’s attention in March. Liberia’s largest newspaper featured a story describing Ebola as a man-made virus being purposely unleashed upon Africans by Western pharmaceutical companies. Reports abound of doctors and other workers being chased away, sometimes violently, by fearful families. …

It’s not a pleasant read but, I think, a necessary one. For anyone who may think the panic and fear are unique to this situation, I once worked with a nurse who described being lifted by her neck after someone came through the door of a clinic demanding a vaccine and had been refused. He was in such a panic and so fearful he wasn’t going to take a ‘no’. The incident took place in Vancouver (Canada) in a ‘nice’ part of town.

ETA Sept. 24, 2014: Kelly Grant has written a Sept. 22, 2014 article for the Globe and Mail which provides more information about Tekmira, some of which contradicts the details I have here about TKM-Ebola and clinical trials in Africa although the key points remain the same. She also provides more information about the ZMapp therapy mentioned in my Aug. 15, 2014 post mentioning yet a third Canadian connection. Canada’s National Microbiology Laboratory was somehow involved in developing ZMApp, unfortunately, Grant does not or is not able to provide more details about that involvement.

ETA Oct. 16, 2014: David Bruggeman recommends a digital journalism site Ebola Deeply for some in depth reporting in his Oct. 16, 2014 posting.