UK company wins global medicine award for its ground-breaking potential MS treatment

A leading scientist battling to halt the development of Multiple Sclerosis has revealed that clinical human trials will start by 2020, after her company was honoured with a major nano medicine award. Dr Su Metcalfe's regenerative nanomedicine company, LIFNano™, was named Most Promising Nanomedicine Project at the International Nano Medicine Awards in Berlin on Tuesday, November 7.

Founded by Dr. Metcalfe, LIFNano™ slowly releases nanoparticles which are forecast to trigger natural healing in the brain. They contain Leukaemia Inhibitory Factor (LIF), to counter the disease process as it attacks the brain and spinal cord.

Dr. Metcalfe, who earned a PhD in pathology at the University of Cambridge, launched the technology company LIFNano™in 2013 and has been recognised many times already in the last few years. She said, upon receiving this global award “It has always been about getting this to patients. We have found evidence in our animal trials showing significant healing of damaged brain tissue in addition to the potent protection of brain cells.” Dr Metcalfe, who is based in Cambridge, England went on to say, “We are honoured to have been selected for this international award, but our absolute focus is ensuring patients see the benefits through clinical trials in 2020.”

Dr. Su. Metcalfe (middle), picking up the Most Promising Nanomedicine Project at the International Nano Medicine Awards in Berlin on Tuesday, November 7.

Battling with Multiple Sclerosis

Multiple sclerosis (MS), is a neurological disease that attacks the brain and spinal cord. It affects more than 2.3 million people around the world and occurs when the immune system attacks the myelin sheath, the protective coating that encases nerve cells. This triggers symptoms such as vision problems, poor balance and muscle spasms. It could lead to total disability and dementia. The disease is forecast to cost in excess of $100 billion annually around the globe.

The issue with current treatments has been that they typically greatly diminish the activity of immune cells and they need to be used on a regular basis. Although these treatments prevent those immune cells from ravaging myelin within the brain, they also leave the body vulnerable to infection. None protects the brain. Metcalfe’s nanoparticles reset and correct the fault that causes MS as they deliver the natural stem cell growth factor LIF, directly and specifically to the sites of nerve damage, and keep the immune system from attacking myelin. They do not impair immunity and allow immune cellsto mobilize against harmful invaders when needed. What’s more, LIF can actually help repair damaged myelin within the brain.

If LIFNano™ holds up in clinical trials, “that would be a really significant addition to the treatments we have,” explained Bruce Bebo, executive vice president of research at the National Multiple Sclerosis Society, in an interview in October with OZY. Another benefit is its targeted approach which means fewer side effects expected, using the naturally occurring LIF.

For patients with MS, the potential of LIFNano™ could be profound once clinical trials have been successfully completed. Indeed, in addition to regulating immunity, a further key role of LIF is to sustain a healthy central nervous system, protecting nerves and maintaining myelin. LIFNano is therefore a powerful candidate for treatment of patients suffering from MS, providing a triple action for healing the brain and protecting nerves, repairing myelin and resettingself-tolerance. The beauty of the technology is its simplicity as it lets the body do what nature intended, slowly releasing LIF via the nanoparticles. Time really matters for MS sufferers, as early treatment is known to slow the course of the disease.

Dr Metcalfe's preclinical research has already found no toxicity of the LIF nanoparticles. Remarkably, LIF itself, the PLGA nanoparticles, as well as the anti-body fragment used to direct them have all been already used, separately, in various clinical trials. 

Quantum Leap Nanomedicine

The nanoparticle manufacture has originally been developed jointly by Dr. Metcalfe and Yale University. Ultimately, Yale granted an exclusive license to LIFNano™ to develop the platform for MS, and for other degenerative diseases such as dementia and for auto-immune conditions, for years to come. The company, which has been self-funded to date, uses safe and natural ingredients rather than synthetic drugs.

LIFNano™ has a stellar team and advisers who are now working with Dr Metcalfe, including its Chairman, Florian Kemmerich, who also heads up the Europe-based NanoMed. The company's CEO, Olivier Jarry, joined the company with executive experience at Novartis, Bayer and Bristol-Myers Squibb, in addition to having consulted for giants such as Pfizer, GSK and Sanofi. Commenting on the award Olivier said, “Our treatment has the curative potential to deal with the root cause of MS, rather than just addressing symptoms and we hope to prove this in our human trials.” He went on to say, “the delivery of LIF across the blood brain barrier could profoundly improve therapeutic outcomes, reducing costs and potentially increasing convenience and safety.”

The Chairman of the company, Florian Kemmerich, said, “We have great partners, solid patents and exclusive licenses. This platform technology could go on to have profound impacts on other diseases such as Alzheimer's. We have received a lot of support and more is coming due to the scalability of the platform. We believe that, by successfully delivering these LIF nanoparticles to the brain, we will enable cells damaged by 'rogue' white blood cells to be repaired. This should then re-balance the body, using the natural reparative immune system we all have.”

The EU's European Technology Platform Awards honour firms that have developed a nanomedicine solution “that could bring significant benefits to patients, changing the way diseases are treated or diagnosed or providing new tools for physicians.” It further supports our drive to reach people with MS quickly. The award has previously been won by the Merck group, for a project aiming to develop a nanomedicine oncology product for mucosal therapeutic vaccination.

LIFNano™ and Dr. Metcalfe can add this to several other awards they have won or have been shortlisted for, including the UK government-backed Innovate UK Smart Award, the Merck Serono GMSI award, the Rolex Award for Enterprise and Business Weekly's Woman Entrepreneur of the Year Award.

The company is currently securing investment to complete GMP manufacturing, and secure authorizations to start clinical trials, aiming at generating a ‘proof of concept’ (Phase IIa) in 2020.

To contact the company or to find out more about the technology go to www.lifnano.com or contact investor-relations@lifnano.com

https://nano-magazine.com/news/2017/11/7/uk-company-wins-global-medicine-award-for-its-ground-breaking-potential-ms-treatment/?email=donpatent@gmail.com

Targeting a single protein might treat a broad range of viruses

November 8, 2017

The measles virus is suppressed (right) when a key protein, SPCA1, is decreased in the host. Credit: Hans-Heinrich Hoffmann

Most drugs that fight viruses are designed to target individual pathogens. But scientists at The Rockefeller University have identified a protein that a broad range of viruses require to spread within a host—a discovery that could lead to fighting viruses as varied as parainfluenza, West Nile, and Zika with a single drug.

All viruses use proteins from the host's cellsin order to replicate. A team in Charles M. Rice's lab has identified a calcium-transporting protein that is needed by many viruses during the later stages of their life cycles. The researchers showed that depleting this protein in host cells significantly impairs the viruses' ability to spread, without harming the cells.

By indicating a way that a single medicine could fight many infections, these advances have the potential to multiply the return on time and effort invested in drug development. The researchers' findings were reported this month in Cell Host & Microbe.

"There's been a push to get broader antivirals, and that's difficult because viruses tend to be very different in what they do, exactly," says Hans-Heinrich Hoffmann, the lead author of the study. "The key to creating a broad antiviral medicine is to find a host protein that many viruses need but that is not essential to the cell's survival. And that's exactly what we found here."

From RSV to Zika

The researchers launched their study by trying to find a host protein required by the human respiratory syncytial virus (RSV), a major virus that is particularly dangerous to children and the elderly, causing an estimated 3.4 million hospitalizations a year. There are currently no vaccines against RSV or specific antivirals that fight it.

Even a partial loss of the protein, the calcium pump SPCA1, limited the ability of many viruses to mature and spread, the scientists found. Cells that lack the protein were also less susceptible to initial infection.

After finding that RSV requires SPCA1, the researchers determined that many other viruses, both insect-borne and respiratory, need the protein. Among those is Zika, the mosquito-borne virus linked to brain malformation in infants. As with RSV, there are no approved antivirals for Zika.

Patients lacking proteins

It is one thing to study whether individual cells can survive without a protein. But to be useful as a therapy, researchers would need to understand how a lack of SPCA1 affects an entire organism—such as an actual patient.

There are, in fact, individuals who have reduced levels of SPCA1, as a result of a rare genetic disorder known as Hailey-Hailey disease. The disease causes skin problems, such as blisters and lesions, but is not life-threatening. Furthermore, cell cultures derived from patients with Hailey-Hailey disease indicate that their cells are less susceptible to certain infections, including RSV—a result that correlates with the researchers' other findings.

"We know that these patients get by with only half the normal amount of the protein, and we have evidence that this may even offer a protective effect," says Rice, who is the Maurice R. and Corinne P. Greenberg Professor in Virology and head of the Laboratory is Virology and Infectious Disease. "It's a promising avenue for drug development."

Explore further: 'Exciting' discovery on path to develop new type of vaccine to treat global viruses

More information: H.-Heinrich Hof Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread, Cell Host & Microbe (2017). DOI: 10.1016/j.chom.2017.09.002

Journal reference: Cell Host & Microbe

Provided by: Rockefeller University

Read more at: https://phys.org/news/2017-11-protein-broad-range-viruses.html#jCp

Study Gives Rare Look at Genetics of HSV1 Transmission from Father to Son

Friday, October 20, 2017

A new study explores how herpes simplex virus might change when passed from one individual to another, information that may prove useful in future development of therapeutics and vaccines.

This rare glimpse into a transmission event reveals nearly perfect genetic transmission of the virus from a father to his son and lays the foundation for future studies exploring the genetic diversity of this virus. A paper describing the study appears online October 20, 2017, in the journal Scientific Reports. It was conducted by scientists at Penn State, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati. 

https://www.nature.com/articles/s41598-017-13936-6

“Millions of people worldwide have herpes simplex virus,” said Moriah Szpara, PhD, assistant professor of biochemistry and molecular biology at Penn State and an author of the paper. “We see locally distinct variants of the virus with distinct genetic fingerprints in different regions around the world, and, with the prevalence of international travel, we’re starting to see a lot of different variants of the virus appearing in one place. This could have implications for how the virus evolves and how we design therapeutics to combat it. Studies of a related virus – human cytomegalovirus – suggest that the virus diversifies after transmission, and we wanted to see if this was also the case for herpes simplex virus.”

Herpes simplex virus type 1 (HSV-1) is a highly contagious infection that commonly causes oral and genital lesions. More severe symptoms can also occur, such as eye disease and, in rare cases, encephalitis -- inflammation of the brain that can cause flu-like symptoms, confusion, seizures, or problems with movement. Although some medications can reduce the severity and frequency of the symptoms, there is no cure for HSV-1 and no guaranteed way to prevent transmission. HSV-1 can be transmitted through contact with sores or saliva around the mouth –  as is often the case in familial transmission – or sexually.

“Capturing transmission of herpes simplex virus is incredibly difficult,” said Szpara, “in part because the social stigma associated with having the virus makes it unlikely for sexual partners to admit when they transmit it. The virus also lasts a lifetime. Unlike the flu, which comes and goes, HSV remains in an individual’s body for the remainder of their life. Periods of latency and reactivation make it hard to know exactly when the virus was first transmitted.” 

“In this study, we had a known case of familial transmission,” said Nancy Sawtell, PhD, professor in Infectious Diseases at Cincinnati Children’s and paper co-author. “Samples from a father and son were cultured in the lab, enabling us to investigate potential differences of the virus after transmission. To gain a comprehensive look at the results of transmission, we used genetic sequencing, and we examined each virus in an animal model to compare the level of virulence, or the ability to cause disease. Animal models have the ability to reflect the interactions of all the body’s systems at once — the outer surface, the immune system, and the nervous system all interact during the response to herpes simplex virus infection.”

Genetically, the viruses taken from the father and son were a near-perfect match. The viruses also had similar pathology when tested in mice – they grew at a similar rate and had a similar ability to set up long-term infection in the brain. Although the viruses from the father and son were not completely identical, these results suggest that HSV-1 may not change much when transmitted between closely related individuals. However, the researchers suspect that transmission between unrelated hosts may provide a more dramatic opportunity for change.

“An individual’s immune system exerts selection pressure on a virus,” said Utsav Pandey, graduate student at Penn State and first author of the study. “The son got at least half of his immune system from his father, so it was probably a similar selective environment. Unrelated individuals likely differ more in their immune system, which could shape the virus.”

The research team also compared the performance of the viruses from the father and son to two separate clinical cultures of HSV-1. The variants from the father and son were less virulent — less severe — when tested in mice. Additionally, the genome sequence of the viruses in the father and son, who were from the United States, did not fit in as expected with other HSV-1 genomes that have been genetically sequenced from the United States or Europe.

“This study broadens our knowledge of what herpes simplex virus variants are circulating in the U.S.,” said Szpara. “It’s not just the United States/European variants that are used in vaccine development and clinical studies. When we think about designing therapeutics and vaccines, we need to know how the virus can differ or we may design something that only controls the virus from a particular region.”

To further understand how genetic diversity of HSV-1 is generated, the researchers plan to turn their attention to studying transmission of the virus between unrelated individuals. “If we could understand how much the virus changes when passed between unrelated individuals and how the virus’ genetics influences the level of virulence or level of harm the virus can do,” said Szpara, “then hopefully we can design better treatments for HSV-1.”

In addition to Szpara and Sawtell, the research team includes Utsav Pandey, graduate student at Penn State; Daniel Renner, computational scientist at Penn State; and Richard Thompson, professor of molecular genetics, biochemistry, and microbiology at the University of Cincinnati. The work was funded by the National Institutes of Health and the Pennsylvania Department of Health Commonwealth Universal Research Enhancement (CURE) program and supported by the Huck Institutes of the Life Sciences at Penn State.

Contact Information

Nick Miller
513-803-6035
nicholas.miller@cchmc.org

https://www.cincinnatichildrens.org/news/release/2017/herpes-simplex-virus

Vivien Boniuk presentation

Will that Vivien Boniuk presentation be published? I hope so - I want to see what the iHub shilling crowd have to say. Besides "It's a scam and a fraud." Ref: shill SHil/ NORTH AMERICAN noun 1. an accomplice of a hawker, gambler, or swindler who acts as an enthusiastic customer to entice or encourage others. verb 1. act or work as a shill. Shill - Wikipedia en.wikipedia.org A shill, also called a plant or a stooge, is a person who publicly helps or gives credibility to a person or organization without disclosing that they have a close relationship with the person or organization.

Reuters VNTH background

NANO MOBILE HEALTHCARE INC

https://www.reuters.com/finance/stocks/overview/VNTH.PK

Uncovering bacterial cell wall secrets to combat antibiotic resistance

NanoViricides has proven it works on viruses so let's see it work on bacteria next!

November 6, 2017

In the battle against drug-resistant bacteria, Marcos Pires studies the chemical biology of bacterial cell surfaces to better understand how they function -- and possibly how to manipulate them Credit: Hvass & Hannibal courtesy of Lehigh University

Cell walls—the jacket-like structures that surround all known bacteria—may turn out to be bacteria's undoing , holding the key to developing new drugs that target it for destruction.

That perspective is shared by many in the medical and scientific communities, including Marcos Pires . Pires, a biochemist at Lehigh University, is spearheading a novel approach to understanding bacterial cell wall changes in response to antibiotics that could be critical to new drug design—an urgent need in light of the growing threat of antibiotic resistance. His approach is so promising it has recently been recognized by the National Institutes of Health with a Maximizing Investigators' Research Award (MIRA).

Antibiotic resistance occurs when bacterial cells adapt to evade a drug designed to kill it. Making changes to the cell wall is one way bacteria accomplish this. Little is known, however, about just how these structures respond when under attack.

With the 5-year $1.94 million MIRA grant, Pires's group will delve deeply into this process through a unique approach that essentially tricks bacteria into revealing where its cell wall is most vulnerable. Such knowledge could help scientists design next-generation antibiotics that circumvent drug resistance mechanisms.

The centerpiece of the research is a process that Pires and his team conduct facilitating live bacteria's absorption of synthetic cell wall fragments constructed in the lab. These fragments are modified with reporter units which then allow researchers to observe, in live bacteria, components of the cell wall machinery under various conditions.

"Bacterial cell walls are unique in their structure and function and are essential to bacterial cells—making them unique targets for the development of antibiotics," said Pires, assistant professor in the Department of Chemistry. "By 'tricking' bacteria into using some of our cell wall building blocks, we get an unprecedented perspective on how they change when challenged with antibiotics."

MIRA is a program of the National Institute of General Medical Science (NIGMS), a division of NIH that provides support for basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention. According NIGMS, the goal of MIRA is to increase the efficiency of NIGMS funding by providing investigators with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs.

Identifying bacterial cell wall changes that cause antibiotic resistance

The stakes for drug design breakthroughs to treat drug-resistant bacteria are high. Every year in the United States, more than 2 million people are afflicted with resistant bacterial infections. An estimated 23,000 American lives—and 700,000 lives worldwide—are lost yearly as a result of bacterial infections resistant to current antibiotic treatments. These numbers are only expected to grow.

Bacterial cell walls are the target of some of the most powerful antibiotics discovered to date. Cell wall-targeting antibiotics include some commonly prescribed treatments such as penicillin and amoxicillin. Drugs that target bacteria's cell walls are also among the safest as human cells do not have cell walls and are thus unaffected by the treatment.

According to Pires, individual components of the bacterial cell wall machinery are key to bacteria's adaptation response and, therefore, to drug-resistance. One of his team's goals is to identify the cell wall components that bacteria need to successfully adapt and evade the drugs designed to destroy it.

"If we can identify these 'weak spots', said Pires, "we should be able to find ways to inactivate or circumvent them."

 Explore further: Even bacteria have baggage—and understanding that is key to fighting superbugs

Provided by: Lehigh University

Read more at: https://phys.org/news/2017-11-uncovering-bacterial-cell-wall-secrets.html#jCp

On the way to a universal antibacterial and antiviral agent

Posted: Jul 11, 2017

Selectively killing bacteria with magnetic nanoparticles (Nanowerk News) Based on previous investigations of nanoparticles as effective antibacterial coating ingredients, scientists at Clemson University hypothesized that multianchored magnetic nanoparticles conjugated with sialic-acid moieties that mimic host-cell receptors specific for Escherichia coli strain K99 (EC K99) adhesins would induce rapid clustering of EC K99 in the presence of these nanoparticles, and when such bacteria-nanoparticles aggregates are exposed to an alternating magnetic field (AMF), it would result in enhanced and selective inactivation/killing of EC K99.

Reporting their findings in Advanced Functional Materials ("Multianchored Glycoconjugate-Functionalized Magnetic Nanoparticles: A Tool for Selective Killing of Targeted Bacteria via Alternating Magnetic Fields"), they demonstrated proof-of-concept multianchored glycoconjugate (Neu5Ac(α2-3)-Gal-(β1-4)Glcβ-sp) GM3-magnetic nanoparticles (GM3-MNPs) that have high affinity to adhesin of EC K99.

TEM images of GM3-MNPs induced bacterial membrane damage of E. coli strains: A,B,E,F) before AMF, and C,D,G,H) after AMF treatment for 120 min. Concentration of MNPs: 650 µg Fe mL-1. Scale bar is 500 nm. (click on image to enlarge)

The team's nanoparticle system can specifically interact with adhesin molecules of EC K99 and cause agglutination through nanoparticle–bacteria complex. Applying treatment with an alternating magnetic field to such complex caused significant reduction in viability of targeted bacteria EC K99 in both pure-culture and mixedcultures settings due to possible highly localized temperature increase.

Exposure to such conditions resulting in compromised membrane integrity of EC K99. Moreover, GM3-MNPs coupled with AMF resulted in significant decrease in the overall intracellular ATP levels of the bacterium.

These results demonstrate that the unique multianchored nanoparticle system in the presence of AMF can be effectively used as novel nonantibiotic platform for local and selective inactivation of the target bacteria in biological systems without affecting the viability of nearby cells/tissues.

This study therefore serves as proof-of-concept that a high degree of selective bacterial killing can be obtained without using traditional antibiotics.

In the event of gastrointestinal tract infections caused by enterotoxigenic E. coli pathogens, administered antibiotics can disrupt/destroy beneficial gut microflora in addition to pathogens. It could cause various side effects in the human body along with giving rise to antibiotic-resistant bacterial strains.

The Clemson team's system can find useful applications in treating such infections in animals and humans and in conditions when administered antibiotics, especially those of the last-line-of-defense drugs, fail to eradicate the infections due to drug-resistance.

"Future studies will involve optimization of particle parameters including nanoparticle core-size and polymer coatings, as well as a detailed investigation on the effects of field strength and frequency to maximize killing rate of clinically relevant multidrug resistant bacterial pathogens," the authors conclude their report. "Additionally, biocompatibility of our nanoparticle system will be evaluated in human cell-lines and small animal models."

By Michael Berger – Michael is author of two books by the Royal Society of Chemistry: Nano-Society: Pushing the Boundaries of Technology and Nanotechnology: The Future is Tiny.

Read more: Selectively killing bacteria with magnetic nanoparticles