Potential treatment for Ebola and other deadly viruses revealed

Ebola virusIllnesses caused by many of the world’s most deadly viruses cannot be effectively treated with existing drugs or vaccines. But this may all be about to change. Scientists have discovered several compounds that can inhibit the highly lethal Ebola virus, as well as the pathogens responsible for rabies, mumps, measles and other pathogenic viruses.

This finding, published in the journal Chemistry & Biology potentially opens up new therapeutic avenues for combating these diseases.

ebola-patientSuch treatments are desperately needed. Ebola virus, for example, can be transmitted through direct contact with blood or other body fluids of infected persons or animals, and even close contact with a deceased Ebola-infected body. And mortality rates from ebola can be as high as 90%.

The medical field currently does not have ideal antiviral therapies, often no therapeutics at all, and the development of broad-spectrum antivirals is a great way to provide treatment in the future,” says study author Claire Marie Filone PhD of Boston University School of Medicine. “Toward that end, we have identified a drug that targets multiple viruses – and may be developed into an antiviral treatment for known and emerging viruses.”

In contrast to the many antibiotics that work against a wide range of bacteria, there are currently no highly effective or safe broad-spectrum drug treatments for viral diseases.

virus cycleTo address this need, researchers screened thousands of diverse compounds for small molecules that showed strong antiviral activity against viruses.  They identified several that inhibited infection in cells exposed to either Ebola or vesicular stomatitis virus (VSV). These molecules, which are related to a class of plant-derived compounds called indoline alkaloids, share a common chemical structure that can be modified to enhance antiviral activity.

The most potent of these compounds demonstrated a consistent mechanism of action against genetically distinct viruses. It works by blocking viral transcription. Because it targets such a critical step in virus replication, in theory, scientists should be able to develop it into a therapeutic that could be used against many different types of viral infections.

As always, SRxA’s Word on Health will bring you further news as it develops.

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Putting the Hilarity in Charity

CUPIDS Undies 1Residents and visitors to the nation’s capital prepare for a big surprise.  No, we’re not talking about the upcoming inauguration, but something altogether more fun. So what could be more captivating than the swearing in of the 57th President you ask?

Well how about 1,000 scantily clad runners?  That’s right!  In less than a month, on Valentine’s day weekend to be exact, the streets of Washington, DC will be filled with belles in bras and boys in boxers.  All will be participating in the third annual Cupid’s Undie Run to raise donations for the Children’s Tumor Foundation (CTF).

Childrens-Tumor-FoundationThe Children’s Tumor Foundation is dedicated to ending neurofibromatosis (NF) through research. NF is a genetic disorder that causes tumors to grow on nerves throughout the body, causing blindness, deafness, learning disabilities and severe chronic pain. NF affects roughly 1:3,000 births in the U.S. Currently, there is no cure and there are frighteningly few treatment options. The Foundation’s mission is to advance peer-reviewed research to develop treatments and cures for NF; support persons with NF and their families by making thorough and accurate information readily available; to assist in developing clinical centers and best practices to improve access to quality healthcare for those who live with NF; and expand public awareness of NF to improve diagnoses, increase understanding of the challenges that NF presents, and encourage support for NF research.

Cupids founders

Cupid’s Undie Run founders Brendan Hanrahan, Chad Leathers, and Bobby Gill

Cupid’s Undie Run was born three years ago after Chad Leathers learned of his brother Drew’s diagnosis of neurofibromatosis.

Since then, the Cupid’s Undie Run has expanded into 17 cities across the US and to Sydney, Australia with the goal of raising more than one million dollars for neurofibromatosis research.  By 2012, they’d surpassed the $100k mark.  This year, their main is to spread Cupid’s love around the country and get folks in new cities excited about the event and the charity.

The Cupid’s Undie Run DC will take participants on a 1.5 mile run past the US Capitol and the Supreme Court.  Pre- and post-run festivities are held at Pour House and Capitol Lounge. Festivities start at noon on Saturday, February 9th 2013*, before runners strip down for the Undie Run at 2pm. Post-race, there will be numerous festivities and awards. Prizes include custom undies, VIP Open Bar, embroidered bathrobes, engraved iPod Nanos, and even romantic getaways.

cupids1Charitable cherubs can either fundraise as an individual or join a team.

In addition to the DC event, there will be Cupid’s undies runs in NYC, Atlanta, Seattle, Denver and Cincinnati, LA, San Fran, Chicago, Austin, Nashville, Orlando, Minneapolis, Philly, Cleveland, St. Louis and Detroit.  Get ready!

So if you’re ready to run 1.5 miles in your bedroom-best click here for more information.

See you in your skivvies!

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Diabetes Drug may Repair Injured Brains

Here’s a good brain teaser for a Wednesday.  What do an old diabetes drug, brain injury and Alzheimer’s Disease have in common?

Here’s some clues to help you solve the riddle.

(i)           Metformin is a widely used treatment for type II diabetes

(ii)          An increasing proportion of people with Alzheimer’s Disease also have diabetes

(iii)         Hyperinsulinemia (excess levels of insulin in the blood) may enhance the onset and progression of neurodegeneration

Have you solved it?  If so, congratulations!

If not, the answer, according to data just published in the journal Cell Stem Cell is that the former may hold the clue to treating the latter.

In other words, the study suggests that metformin, an anti-diabetes drug first discovered in the 1920’s, is able to help activate the mechanism that signals stem cells to generate brain cells.

Principal investigator, Freda Miller, a Professor from the Department of Molecular Genetics at the University of Toronto
says “If you could take stem cells that normally reside in our brains and somehow use drugs to recruit them into becoming appropriate neural cell types, then you may be able to promote repair and recovery in at least some of the many brain disorders and injuries for which we currently have no treatment.”

The research involved laboratory experiments using both mouse and human brain stem cells, as well as learning and memory tests performed on live mice given the drug.

Miller and her colleagues started by adding metformin to stem cells from the brains of mice, then repeated the experiment with human brain stem cells generated in the lab. In both cases, the stem cells gave rise to new brain cells.

They then tested the drug in lab mice and found that those given daily doses of metformin for two or three weeks had increased brain cell growth and outperformed rodents not given the drug in learning and memory tasks.

In the key experiment, mice were forced to learn the position of a platform hidden under the surface of a water-filled maze and then asked rapidly to learn a new position.

Mice were injected with either metformin or saline for 38 days. On days 22 through 38, they learned the initial position of the platform, which provided an escape from the water-filled maze.  Then the platform was moved to the opposite side of the maze, and the animals were asked again to learn its position. In both tasks, the mice learned the platform positions with equivalent speed.

But when they were put back in the maze – this time with the platform removed – control mice spent more time searching for it in the original position, while the metformin-treated animals preferentially looked in the new region.

The implication  is that metformin helped the mice form their new memories of the second platform position. Further analysis showed that their enhanced ability was paralleled by an increase in the number of  neurons.

In a separate study researchers have shown that metformin can increase lifespan and delay the onset of cognitive impairment in a mouse model of Huntington’s disease.

Taken together, these findings raise the possibility that metformin’s ability to enhance neurogenesis might have a positive impact in some nervous system disorders.

Miller’s team is already planning a pilot study to test metformin in young patients with acquired brain damage, either as result of treating a childhood brain tumor or from a traumatic head injury.

We will report back to you with results, as they are published.

The King Provides Clues to Human Emotion

Last year, while waiting to catch a plane from Washington DC to San Antonio TX, I was joined by a young gentleman, around 24 or 25 years of age and his super-glamorous mom. Initially I was somewhat surprised that they had chosen to sit right next to me, given that the departure area was otherwise empty.

Within seconds he had struck up a conversation, within minutes I was practically his new BFF and before the flight was called he was holding my hand, whispering in my ear and grinning like a teenager.

Before you start thinking “wedding bells” or “cougar time”, what I learned from his mom, was that he had Williams syndrome. What I learned later, after googling the condition, was that people with Williams syndrome have an unusually gregarious personality. They view everyone as their friend, and it’s not unusual for them to rush up to total strangers and strike up conversations as though they are old acquaintances.

Those with the disorder look at the world through a unique lens. Despite their desire to befriend people they have high levels of generalized anxiety poor social judgment, disturbed peer relationships and altered responses to fearful and happy faces.  Their average IQ is 60, they experience severe spatial-visual problems, and suffer from cardiovascular and other health issues. They also have an affinity for music.

This week, I learned that the latter trait is helping scientists shed light on the mystery of emotion and human interaction. Social and emotional responses are so fundamental to human behavior that they are often taken for granted. However, the genetic and neurobiological bases of social behavior are largely unknown, as are the mechanisms for disruptions in social behavior and emotional regulation that appear throughout the lifespan as features of mental illnesses.

In a study led by Julie R. Korenberg, Ph.D., M.D. one of the world’s leading experts in genetics, brain, and behavior of Williams syndrome, people with and without Williams syndrome listened to music while researchers  gauged emotional response by measuring the release of oxytocin and arginine vasopressin – two hormones associated with emotion.

The study, published in PLoS One, signals a paradigm shift both for understanding human emotional and behavioral systems and expediting the treatments of illnesses such as Williams syndrome, post-traumatic stress disorder, anxiety, and possibly even autism.

The study is also the first to reveal new genes that control emotional responses and to show that arginine vasopressin is involved in the response to music.

The trial involved  21 participants – 13 with Williams syndrome and a control group of 8 without the disorder. Before the music was played, participants’ blood was drawn to determine a baseline level for oxytocin. Those with Williams syndrome had three times as much of the hormone as those without the syndrome.

Blood also was drawn at regular intervals while the music played and was analyzed afterward to check for real-time changes.

While other studies have examined how oxytocin affects emotion when artificially introduced into people through nasal sprays, this is the one of the first significant studies to measure naturally occurring changes in oxytocin levels in rapid, real-time as people undergo an emotional response.

Researchers asked the first participant to listen to the 1950’s Elvis Presley classic, “Love Me Tender.” The woman showed no outward response to the song. So, to elicit a greater response from the remaining study participants, the researchers invited them to bring along their favorite music.  Many of them chose heavy metal, but again, there was little outward response to the music.

However, when the blood samples were analyzed, they showed that oxytocin levels, and to a lesser degree arginine vasopressin (AVP), had not only increased but begun to bounce among the William syndrome group. In contrast, both oxytocin and AVP levels remained largely unchanged as those without Williams syndrome listened to music.

Interestingly, the oxytocin level in the woman who’d listened to “Love Me Tender” skyrocketed compared to the levels of participants who listened to different music.

Korenberg believes the blood analyses strongly indicate that oxytocin and AVP are not regulated correctly in people with Williams syndrome, and that the behavioral characteristics unique to people with the condition are related to this problem.

To ensure accuracy of results, study participants were also asked to place their hands in 60° Fahrenheit water to test for negative stress. The same results were produced as when they listened to music. Those with Williams syndrome experienced an increase in oxytocin and AVP, while those without the syndrome did not.

In addition, study participants took three standard social behavior tests that evaluated willingness to approach and speak to strangers, emotional states, and various areas of adaptive and problem behavior. Those test results suggest that increased levels of oxytocin are linked to both increased desire to seek social interaction and decreased ability to process social cues.

The association between abnormal levels of oxytocin and AVP and altered social behaviors found in people with Williams Syndrome points to surprising, entirely unsuspected deleted genes involved in regulation of these hormones and human sociability,” Korenberg said. “It also suggests that the simple characterization of oxytocin as ‘the love hormone’ may be an overreach. The data paint a far more complicated picture.”

However, the results of the study offer great hope. By regulating levels of oxytocin and vasopressin it should be possible to relieve suffering and improve the lives of those with Williams syndrome.

In the meantime, this study certainly brings new meaning to the phrase “mood music.”

The biggest-selling drug in 2018 will be…

EvaluatePharma, a UK based company specializing in pharma and biotech analysis has been gazing long and hard into its crystal ball.

Having scrutinized the world’s leading 3,500 pharmaceutical and biotech companies they have come up with a list of what, they believe, will be the top 10 selling drugs in 2018.

  1. Januvia       (diabetes) – $9.7 billion
  2. Humira        (arthritis) – $8.2 billion
  3. Avastin        (cancer) – $7.5 billion
  4. Enbrel          (arthritis)  – $7.2 billon
  5. Revlimid     (myelodysplastic syndrome) – $6.75 billion
  6. Prevnar 13  (pneumococcal vaccine) – $6.72 billion
  7. Rituxan         (cancer) – $6.3 billion
  8. Lantus           (diabetes) – $5.9 billion
  9. Remicade     (arthritis) – $5.8 billion
  10. Advair            (COPD)  – $5.7 billion

Surprised?  No conventional molecules, no cholesterol lowering agents, no blood pressure meds and not a single new drug among the top ten.  However, they predict the #11 best seller will be GS-7977 – the much anticipated oral hepatitis C drug from Gilead Sciences .

Not so surprising, given the obesity epidemic sweeping the western world that 2 of the front runners are diabetes drugs. Likewise, given the globally aging population – 3 are for arthritis.

#5 may be a surprise to many. Few people had ever heard of myelodysplastic syndrome before ABC news anchor Robin Roberts announced last week that she has the disease.  Still, it’s predicted number 5 status doesn’t mean that an epidemic is expected – it’s still relatively rare with only 10,000 or so new cases detected each year. Its lofty status on the list is more to do with the price. It costs a staggering $10,000 or so for a 28 day supply of the pills.

Other predictions from the EvaluatePharma World Preview 2018 report:

  • Worldwide prescription drug sales are forecast to total $885bn in 2018 an increase of 3.1% from 2011
  • Over $290bn of pharmaceutical sales are at risk from patent expirations between now and 2018
  • Pfizer was the top company for prescription drug sales in 2011, but  Novartis will top the list by 2018
  • Global pharmaceutical R&D spend forecast will grow by 1.5% per year to $149bn in 2018
  • Anti-coagulants (blood thinners) are set to record highest growth of major therapy categories to 2018

Interesting stuff. But the problem with such long term predictive models is that they are but a snapshot  trying to project out six years.

In reality, life is a movie, with a frequently changing plot. For example if J&J’s canagliflozin can reduce obesity and improve blood sugar levels better than Januvia then the projected No. 1 ranking is suspect, at best.

You Can Teach an Old Drug New Tricks

Drug discovery is a laborious process.

From initial discovery of a promising target to the final medication becoming available, is an expensive, and lengthy process. At present, the costs of bringing a single new drug to market is around $1.2 billion, an amount that doubles every five years.

Aside from the cost, it takes, on average, 12 years for an experimental drug to progress from bench through FDA approval to market.

Annually, North American and European pharmaceutical industries invest more than $40 billion to identify and develop new drugs. Even so, for every 5,000 compounds that enter pre-clinical testing, only five, on average, are tested in human trials, and only one of these five receives approval for therapeutic use.

So, it’s hardly surprising that many pharmaceutical companies are choosing to take a closer look at old drugs. Last week, SRxA’s Word on Health brought you news of a host of potential new uses for aspirin.

And aspirin is not alone.  Old drugs often get a surprising second shot at life. In the past few weeks, the news has buzzed about the skin cancer drug – bexarotene – that may cure Alzheimer’s; a common antimalarial drug – hydroxychloroquine – that may help to destroy cancerand, a leukemia drug that inhibits the Ebola virus.

Then, of course, there’s the personal favorite of many women – Latisse.  Originally developed as a glaucoma treatment , it was found to have the desirable side effect of making eyelashes fuller and longer and is now FDA approved for this purpose.

Testing drugs already approved for one use to see if they can treat other conditions, can reduce time and money. Since these known drugs have already undergone toxicology and safety testing, the clinical development program can be streamlined.

Sometimes it’s pure serendipity.

Take Viagra for example. Although these days it’s the stuff of pharmaceutical industry legend , in the early 1990s, it was just a chest pain drug that wasn’t performing very well in clinical trials. So how did the little blue pill go from heart to crotch?  Pfizer was ready to call it quits when they decided to look into one unexpected but common side effect: long-lasting erections. Then came the drug patent and the rest is history.

The discovery that lithium could be used to treat manic episodes in bipolar patients was equally fortuitous. In 1949, Australian psychiatrist John Cade was injecting guinea pigs with urine extracts from schizophrenia patients to try and isolate a compound that caused mental illness. By accident he happened to use a compound with lithium – which at the time was used as a treatment for gout, as the control. Although he didn’t find the compound that caused mental illness, he did find one that treated it!

Back in 2010 we reported on the repurposing of thalidomide. Although the drug caused serious birth defects when it was launched in the 1960’s as a morning sickness pill it has since been found to be useful in reducing severe and frequent bleeding in patients with  hemorrhagic telangiectasia (HHT); in the treatment of patients with newly diagnosed multiple myeloma when taken  in combination with dexamethasone; and for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum

The National Institutes of Health (NIH) recently established The Learning Collaborative (TLC) to study how to more easily repurpose known drugs to treat rare forms of blood cancers.

TLC is a dedicated collaboration between the NIH Chemical Genomics Center (NCGC) and its Therapeutics for Rare and Neglected Diseases (TRND) program, The Leukemia & Lymphoma Society (LLS), and Kansas University Cancer Center (KUCC) to discover and develop new drug therapies for rare blood cancers. TLC is creating a pipeline of new therapies to treat leukemia from both the discovery of new treatments as well as identifying new uses for approved and abandoned drugs.  For example, Auranofin, a drug originally used for rheumatoid arthritis, is now in clinical trials for treating chronic lymphocytic leukemia.

Word on Health will continue to follow the drug recycling trend and bring you news as it breaks. In the meantime if you have noticed any beneficial side effects from the medicines you’re taking, we’d love to know.

Rare but Strong Together

Happy February 29th!  A rare day that comes only once every 4 years. Talking about rare – today is also Rare Disease Day.

In the US, a rare disease is defined as one that affects fewer than 200,000 people.  However, as it turns out rare diseases are actually not all that rare.  In fact there are nearly 7,000 rare diseases affecting almost 30 million Americans. In other words, as many as one in ten Americans are suffering from a rare disease.

Most of my life, I have been involved in some capacity with rare diseases, some of them very rare indeed. While working in the field of transfusion medicine, I became something of an expert in factor II deficiency. This is is an inherited bleeding disorder caused by reduced activity of factor II (prothrombin). Characterized by muco-cutaneous bleeding symptoms, less than 50 people worldwide have been diagnosed.

My work has also brought me into contact with the patients and families affected by a number of rare primary immune deficiency diseases. Most notably among these – ataxia telangiectasia (A-T).  A-T is a progressive degenerative disease marked by ataxia (a lack of muscle control that results in wobbliness and slurred speech); telangiectasia (tiny red spider veins which appear in the eyes, ears or cheeks); immunodeficiencies (low levels of antibodies resulting in increased susceptibility to infections) and a predisposition to cancers such as lymphoma and leukemia.   A-T is thought to affect less than 100 families in the US, and I have been fortunate and humbled to meet most of them. The pictures of some of these children sit on my desk and serve as a daily reminder of why I do what I do. Their daily challenges remind me how inconsequential are my own.

More recently, my EMS work brought me into contact with Hunter syndrome (mucopolysaccharidosis type II). Hunter syndrome is an inherited disease in which the patient lacks an enzyme  (iduronate sulfatase) to break down complex sugar molecules (mucopolysaccharides). As such, sugars accumulate in various body tissues causing severe mental retardation, spasticity, enlarged organs, cardiac defects and deafness. Less than 2,000 people are affected worldwide, fewer than 500 of them in the United States.

Besides dealing with their specific medical problems, people with rare diseases often struggle to get a proper diagnosis and treatment.  Rare Disease Day is about increasing the recognition of rare diseases as a global health challenge and raising awareness of the common challenges and experiences faced by rare disease patients and families.

Rare Disease Day was first observed in Europe in 2008. In 2011, over 60 countries participated and it is hoped that even more will do so this year.

For 2012, the focus of rare disease day is solidarity and the official slogan is “Rare but Strong Together”.  The main aims include:

  • Extensive media coverage
  • Social networking blitz
  • Creating a Rare Disease Physician Database
  • Encouraging patients to share their stories, videos, photos, and blogs including to their local media and through social media
  • Joining hands with others worldwide
  • A three day advocacy and awareness event in Washington, DC at the FDA, NIH and on the Hill
  • Support in-school initiatives in high school biology classes and middle and elementary school classes to implement grade appropriate lesson plans for rare diseases
  • Create tool kits that can help individuals and organizations plan and implement events and awareness activities focused on rare disease day
  • Establishing online photo galleries for the “Handprints Across America” and “Visions of Solidarity” initiatives for patients to express their view of international solidarity in the rare disease community and show the support across the country for this day
  • Update a portal for a user-friendly system to send letters to Congressional Representatives so patients can teach their legislators “Rare Diseases 101”

To find out more about rare diseases and the activities going on today in your area please visit the Rare Disease Day Website.