Month: October 2012

Billions are spent every year in advanced economies on drugs for Alzheimer’s disease, yet none of these drugs can halt or even delay its progression. The story is similar for schizophrenia: billions spent annually on drugs to treat the psychoses that torment schizophrenics, but no approved drugs for the cognitive impairment that is the real impediment to patients’ productive engagement in society.

Here are two enormous opportunities to help millions of patients and their families and to save billions in public health care costs. Everyone knows the largest international pharmaceutical companies – the so-called Big Pharma – are constantly looking for blockbuster drugs to replace revenue from others that continue to fall off their income statements – and these two opportunities certainly qualify. So what is our emerging company, Allon Therapeutics Inc., doing in the thick of this race?  Interestingly, we are not getting run over. In fact, we seem to be among the leaders at the front of the pack.

In numerous animal studies, we have shown that our drug, davunetide, halted brain cell degeneration and improved memory. In a clinical trial in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s, davunetide had a statistically significant positive impact on memory. In a clinical trial in schizophrenia patients, davunetide demonstrated it could improve the capacity for daily functioning of these patients. In that same study, we showed through imaging that davunetide had a statistically significant impact on an important chemical marker of brain cell health.

These trials were carried out by some of the top physicians and researchers in the world and reported at the leading scientific conferences and in journals. Our journey began six years ago when a number of us met the founder of Allon, Professor Illana Gozes.

Davunetide and related compounds were discovered by Prof. Gozes, of the Sackler Faculty of Medicine at Tel Aviv University. Her work was supported by visionary philanthropists, Tel Aviv University, and the US National Institutes of Health (NIH). Prof. Gozes derived davunetide from a naturally occurring neuroprotective brain protein that she discovered, known as activity dependent neuroprotective protein (ADNP). Prof. Gozes, with her colleagues at Tel Aviv and the NIH, demonstrated the significant potential of davunetide in numerous models of Alzheimer’s and neurodegeneration. It was clear then, and is even clearer today, that davunetide could be the leading therapy in the so-called tau pathway of Alzheimer’s and dementia. At the time, however, the generally accepted scientific focus was on other approaches.

We decided to build a business around the significant potential that we saw regardless of industry’s focus elsewhere. We made this decision based on the first principle of biotechnology: follow the data. These data were compelling then and have become even more so after numerous human clinical trials. While following the data is the first principle, we built a business based on common sense.  That is: it’s all about people. We assembled an outstanding team with deep scientific, drug development, and business experience. The team works effectively together, does what it says it’s going to do and, most importantly, shares a passion to help patients and families suffering from cruel and debilitating disease.

Over the past six years, our team has consistently produced animal studies with compelling data in models for Alzheimer’s, schizophrenia, frontotemporal dementias, peripheral neuropathy, and other learning and memory deficits. We’ve shown that our lead drug candidate works in humans, that it works in a way relevant to the patients we’re committed to helping, and we can measure its impacts directly in the human brain. We’ve worked with, and been supported by, the key opinion leaders and public institutions.  

Yet we still have to get this product approved, and studies in Alzheimer’s are long, difficult, and expensive. More disheartening is the fact that it has been about eight years since a novel therapy was approved in Alzheimer’s. In the meantime, there have been numerous high profile and expensive failures. There appear to be basic questions about the approval path, the heterogeneity of the Alzheimer’s population, and the tests used to prove efficacy.

We began to look for a unique and more rational approach – and that is when we learned about progressive supranuclear palsy (PSP), a type of frontotemporal dementia (FTD). Approximately 20,000 and 50,000 people are diagnosed with PSP annually in the US and EU respectively, and it is often characterised by progressive difficulty with balance and walking, eye movement abnormalities, and cognitive and personality changes. Patients are typically diagnosed when they are 45 to 65 years old. PSP is associated with progressive disability and death often a little more than three years following diagnosis.

FTD, including PSP, gradually damages or shrinks the front of the brain – the frontal and anterior temporal lobes. Patients gradually lose the ability to behave appropriately, empathise with others, learn, reason, make judgments, communicate and carry out daily activities. FTD affects approximately 200,000 people in the EU, and a similar number of Americans, or about 6.7 people per 100,000 among people ages 45 to 64.  In people under the age 60, FTD is the most common cause of early-onset dementia. FTD can be mistaken for Alzheimer’s disease, Parkinson’s disease, or a primarily psychiatric disorder like depression, manic-depression, obsessive-compulsive disease, or schizophrenia. There is no efficacious therapy for these patients.

A clear path to approval
We believe that an efficacy study in PSP is not just a unique approach – it is also the right one for Allon and davunetide. We are about to launch a robust human clinical trial in PSP because:

• Our existing data support the hypothesis that davunetide works on tau impairment (or “tauopathies”);
• PSP patients are an homogenous population all of whom have the tau pathology on which davunetide seems to work;
• Sadly these patients decline very quickly and there is no effective therapy; and
• There is a validated rating scale that measures clinically relevant outcomes.

Given these facts, we also believe that our study for davunetide in PSP can qualify for single study approval – meaning that this next study may well be the last required before we ask regulators to approve davunetide for PSP. And regulators have responded positively to this point: davunetide has been granted Orphan Drug status in the US and EU, and it has been given Fast Track status in the US as well. The medical community has responded similarly. We are pleased that one of the world’s leading FTD medical teams, from the University of California San Francisco Memory and Aging Center, as well as many other key medical leaders, has been actively engaged with us.

It is also important to note that this next trial will not just provide data for a potential approval,  it will also help define the opportunity in other tau-related diseases, such as several other types of FTD, as well as Alzheimer’s and schizophrenia. This unique approach may well lead to davunetide being the first approved therapy that actually modifies these diseases. More importantly, we believe that it may bring hope and relief to millions of people and families suffering with cruel and debilitating neurodegenerative disease.

Further information: www.allontherapeutics.com

New findings in people build on studies in rats that showed that reactivating a memory – by showing people objects that stimulate the fearful memory – opens up a specific time window in which the memory can be edited before it is stored again.

“Before memories are stored, there is a period where they are susceptible to being disrupted,” said Elizabeth Phelps of New York University, whose study appears in the journal Nature.

Earlier studies have shown that drugs can be used to block fearful memories, but the results were not long lasting.

Phelps and colleagues based their studies on findings in rats that showed that old memories can be changed or reconsolidated, but only during a specific window time after the rat is reminded of the fearful memory. That window of susceptibility is typically between 10 minutes after re∞exposure to the object to six hours later, when the memory stored once again in the brain.

The researchers applied these findings to people in a lab setting. First, they created a fearful memory by showing the volunteers a blue square, and then delivering a mild shock. Once they had created the fear memory, they simply showed a blue square, which reminded them of the fear memory.

The team waited 10 minutes and then started a training period where the volunteers were repeatedly exposed to the blue square without a shock.

Phelps said simply delaying the exposure training so that it falls within a period during which the memory is susceptible to being edited made a lasting difference in the ability to block the fear memory. A second group that was exposed to the blue square without the ten minute waiting period, continued to show fear when exposed to the blue square.

When they brought people back a year later, the group that got the training showed no fear response – tracked by changes in the skin – when exposed to the blue square, while other volunteers continued to have a fear response.
Phelps said the important aspect of the study is the time window.
   
“What we think is happening is because we did it at the right time, you are restoring the memory as safe as opposed to just creating a new memory that competes with the old memory,” Phelps said.

She said the findings are the first of their type in humans, and she cautioned that the findings cannot be immediately applied to people with severe anxiety problems, such as post traumatic stress disorder.

“We did a blue square with a mild shock,” she said. “Normal fear memories are way more complex than that.”

But she said, the findings do open up the possibility of new training methods that can be studied to help people overcome difficult memories.

“It’s really exciting for the potential of treating these disorders. It’s just a ways away,” Phelps said.

The study was supported through a grant by the National Institutes of Health’s National Institute of Mental Health.

Despite the advances that medical science has made over the years, new drugs are still tested in a very low-tech way: researchers give them to animals.

Animal experimentation still plays a key role in a wide range of scientific disciplines. This is hardly ideal. For one, we are not rats, mice or monkeys: we are people.

Just because a dog hasn’t reacted badly to a trial drug, that doesn’t mean that a human tester won’t. Animal experimentation is also expensive and, depending on your point of view, cruel.

Scientists using animals in their work frequently receive death threats and find it increasingly hard to secure private sector funding: anti-vivisection campaigners learned in the 1990s that targeting investors was an effective way of  
limiting research.

The demand for an alternative to animal testing is clear, and researchers from 13 European universities are working on what they believe will be the solution: a computer simulation of the entire human body.

The Virtual Physiological Human Project is being funded to the tune of €72m by the EU. The idea is to bring together the masses of patient-specific genetic data being gathered across European research institutions.

With advances in computing power and information technology, there is the potential to use a human simulation to develop tailored clinical treatments for patients, based on their unique genetic profile.

If it works, the project could revolutionise medical science in the 21st century. And this is not just a long-term goal, the researchers working in this field say.

They expect to make substantial advances in this field over the next ten years in a range of diseases, from cancer to HIV/AIDS. It could mean the end of animal testing and eventually even clinical patient drug trials.

Kelly BéruBé, a cell biologist from Cardiff University, told a recent conference that the advances in this technology were now moving very fast, and offered the prospect of enough quantitative data to allow much greater use of “virtual tests” in the next decade.

Steven Manos, a computational scientist at University College London, agreed that the project will lead to more effective treatments.

But he cautioned that even the most sophisticated computer models represented only a small fraction of the complexity of animals.

Real reduction in the use of animal experimentation would, therefore, be a long-term goal, he said.

At just 28, Duncan Casey has already been from the university science bench to the world of Big Pharma research and back again. Now working in an Imperial College lab tucked behind London’s famous Science Museum, he has no illusions about the prospects for researchers in the pharmaceutical industry

“The unit I used to work in – GlaxoSmithKline’s place in Harlow – has been closed down now,” says Casey, dressed in signature protective goggles and white coat as he works on synthetic chemistry. “It used to be a job for life. Now it’s a job until the next restructuring.”

Across the western world, Big Pharma is cutting back on the number of scientists it employs in its labs and the money it spends on research and development. The hunt for new drugs continues, but the men and women in white coats – traditionally viewed as the lifeblood of the industry – are not as untouchable as they once were.

It’s a similar story at GlaxoSmithKline’s research laboratories in Verona, where lunchtime conversations can be decidedly gloomy. Glaxo is axing the Italian facility, shedding 500 jobs as part of a programme of cuts designed to improve returns on R&D. Many scientists feel stranded or wonder why they entered the profession at all.

“It’s a sad but true fact that science really doesn’t pay any more,” says one young researcher who would not give her name for fear of jeopardising her future prospects in the industry. “The lunchtime discussion today was about what we’d go back and study if we were 18 again and choosing university courses. There were only a few of us who said they’d still go for a science degree.”

Across the Atlantic in Cambridge, Mass., Adrian Ivinson, director of Harvard’s NeuroDiscovery Centre, is reminded of the shifts underway in the industry every time he looks out of his window. Over the road, the “gorgeous, state of the art labs” no longer house Merck & Co Inc’s neuroscience team. “They only built it a few years ago and had this wonderful neuro group in there,” Ivinson says. “Now they’re gone.”

The magnitude of the changes is hard to ignore.

US drug giants Pfizer Inc and Merck have slashed thousands of jobs since acquiring smaller rival firms last year. British-Swedish firm AstraZeneca has plans to close its research labs at Charnwood in central England by the end of 2011, with the loss of up to 1,200 jobs; its Swedish research unit in Lund will also shut. In Japan, Astellas Pharma Inc has announced plans to limit its research expenditure.

Sam Isaly, managing partner at OrbiMed Advisors – with some $5bn under management it is one of the world’s largest healthcare investment firms – expects employment in the 14 Big Pharma companies across the US, Europe and Japan to fall around 20 percent between 2009 and 2015. That means some 200,000 jobs will disappear across the drugs business – not only in research but also in sales and back office functions. “The management of these companies have to deliver to their shareholders, so they are downsizing or making acquisitions or diversifying,” says Isaly.

New products, new markets
One factor forcing Big Pharma to rethink its business model is the huge number of patents that are set to expire over the next five years. As patents run out on blockbuster prescription tablets like Pfizer’s $12bn-a-year cholesterol medicine Lipitor and AstraZeneca’s $5bn heartburn pill Nexium, cut-price generics are sure to rush in and slash margins. Between now and 2015 products with sales of more than $142bn will face copycat competition, according to IMS Health, the leading global supplier of prescription drug data. It is the biggest “cliff” of patent expiries in the history of the pharmaceuticals industry.

Add in tougher regulatory hurdles and a brutal squeeze on healthcare budgets as cash-strapped governments push austerity programmes and it’s little wonder that drug companies are cutting back and shifting focus.

The strategy so far has been to buy promising new drugs from outside developers and boost investment in the relative safety of non-prescription consumer products. Big drugmakers are also moving into new markets – with Asia at the top of everybody’s list. It all adds up to a redesign of the multinational pharmaceutical company. In the 21st century, says Isaly, Big Pharma will primarily be a distribution business.

Horlicks helps CEO sleep at night
A peek inside the bag of free goodies handed out to shareholders at Glaxo’s annual meeting in London gives an idea of one direction the industry is headed. Aquafresh toothpaste, Corsodyl mouthwash, Breathe Right nasal strips and Lucozade energy drink are not exactly at the cutting edge of bioscience, yet they are all products that now enjoy top billing under Glaxo’s youthful Chief Executive Andrew Witty.

Under Witty, who has been in the top job for two years, over-the-counter remedies, oral care and health drinks have become a key pillar of Glaxo’s drive to reduce reliance on traditional prescription pharmaceuticals. As if to emphasise that fact, the one new hire highlighted by the CEO in his address to the meeting was Emma Walmsley – an executive poached from French cosmetics group L’Oreal SA and heir apparent to run Glaxo’s reinvigorated consumer healthcare business.

Glaxo may be working on groundbreaking treatments for cancer, but one of Witty’s favourite products is Horlicks, a malted milk powder best known in Britain as a bedtime drink for the elderly. Horlicks is a huge seller in the key emerging market of India. The brand clocked up £146m ($214m) in Indian sales in 2009, bagging an enormous 48 percent of the hot drinks market there.

The latest in a string of deals in developing markets gives Glaxo a portfolio of branded generics covering therapeutic areas such as cardiovascular, gastroenterology, metabolic and urology.

Phoenix also brings Glaxo a factory near Buenos Aires, a primary care sales force and pipeline of additional branded generic medicines.

Emerging markets are the new battleground for the world’s top drugmakers as sales stall in Western markets – and Glaxo has vowed to increase its business, partly by moving into the sale of off-patent branded medicines.

Phoenix had sales last year of around £70m ($102m), ranking it number eight in Argentina’s pharmaceutical market, while Glaxo’s Argentine business had revenue of £100m. Combined, GSK Argentina and Phoenix would rank third in the Argentine market.

“This is an important step forward in our strategy to grow our business in Latin America – a key group of emerging markets for GSK,” said Abbas Hussain, the company’s head of emerging markets.

Following the acquisition, GSK Argentina and Phoenix will remain separate legal entities.

In May, Glaxo agreed to buy a 9.9 percent stake in South Korean group Dong-A Pharmaceuticals for £73.9m, the latest of a string of deals designed to increase its share in up-and-coming markets worldwide.

Other deals have included the acquisition of branded generics from both Bristol-Myers Squibb and UCB, as well as product development and distribution deals with Dr Reddy’s of India and South Africa’s Aspen Pharmacare, it which it also has an equity stake.

The balance of the pharmaceutical market is expected to shift significantly toward emerging markets in the next five years.

IMS Health, a leading provider of prescription drug data, forecasts drug sales growth in leading emerging markets will average 14-17 percent annually, while major developed markets grow three to six percent.

Argentina is the eighth largest of the emerging markets for drugs, with a total market value of $3bn and the third highest growth rate at 22 percent, according to IMS.

Eisai’s eribulin added an average of two and a half months to the lives of patients dying of breast cancer, which is a big improvement in such seriously ill cancer patients, the international team of researchers said.

The results of the Phase III trial, presented to a meeting of the American Society of Clinical Oncology in Chicago, have been anticipated after Eisai was given priority review June 1 for US Food and Drug Administration approval of the drug.

“This is potentially practice changing,” ASCO president Dr Douglas Blayney said in a telephone interview.

Dr Christopher Twelves of St James Hospital in Leeds in Britain and an international team studied 762 breast cancer patients with different types of tumor.

All had cancer that had spread and been through at least two rounds of chemotherapy. Two-thirds got two doses of eribulin while getting standard treatment, usually with one other chemotherapy drug but occasionally with just supportive care to treat pain and other symptoms.

The other third got either a third round of chemotherapy or supportive care. “Once this treatment fails, the patient often died,” Blayney said.

The patients given eribulin did considerably better, the researchers told the meeting. The eribulin patients lived a median of 13 months, compared to just under 11 months for patients who did not get eribulin.

Longer lives
Most cancer trials look for what is called progression-free survival, meaning the doctors are looking to see if the tumors start growing back, or sometimes just response rate, to see if the tumors shrink at all.

This one looked to see how long the patients actually lived.

“This study is the first to compare overall survival with this new chemotherapeutic agent to real-life choices in heavily pretreated patients with metastatic breast cancer,” Twelves and colleagues said in their written presentation.

The drug works on the same principle, but with a slightly different mechanism, as older cancer drugs called taxanes and is infused intravenously.

Other experts said eribulin could be one of the last new chemotherapy drugs, which typically target fast-growing cells that include tumors but also healthy cells.

“This is the era of targeted therapy. It’s not an era of chemotherapy,” said Dr Eric Winer of Harvard’s Dana-Farber Cancer Institute in Boston, who was not involved in the study.

“I don’t know that there are going to be many more chemotherapy agents approved for women with breast cancer. That said, this may be one of the last, and potentially provide women with an additional option and maybe an option to be used in combination with targeted therapies in the future.”

Three other studies presented to the meeting showed eribulin was effective and tolerated in a different group of patients with breast cancer, as well as colon cancer and urinary cancer patients.

Eisai has filed in Japan, the US and Europe for approval of eribulin. The company hopes it will become a blockbuster, with global earnings of $1bn a year.

“I think there is a reasonable chance that this drug will actually get approved,” Winer said. “There aren’t many drugs that show a survival advantage in this setting.”

Exact’s test is non-invasive and will be significantly less expensive than a colonoscopy, the current screening gold standard. As President and CEO Kevin Conroy explains in addition to saving lives, conservative estimates show a potential US market of more than $1bn.

Inside the laboratories bustling with activity at Exact Science’s
Madison, WI headquarters, my team’s mission is clear – to save lives by
making the detection of colorectal cancer patient-friendly and accurate.
Everyone who works at Exact Sciences knows the terrible statistics;
more than six hundred thousand people around the world die each year of
colorectal cancer. That’s the equivalent of fifteen hundred 747s
crashing with no survivors. The numbers are enormous, but each case also
represents a person, a parent, a spouse, a sibling, and that is
something that is never far from our minds.

Despite the enormous death toll from colorectal cancer, there is reason for hope. If detected at early stages before symptoms occur, cure rates are very high. And if pre-cancerous polyps can be detected, colorectal cancer can be effectively prevented. The tumour starts as a precancerous polyp, which typically grows over ten to 15 years before becoming a cancer. So, if such polyps can be detected, colorectal cancer can be prevented.

Today, more than half of all colorectal cancers are detected because the patient is experiencing symptoms. In most of these cases the tumours are at advanced stages, survival odds are decreased and treatment options are more costly and severe. The bottom line is that outcomes from this dreaded disease can be greatly improved with effective screening. We believe that a patient-friendly test that reliably detects cancers and pre-cancers will help save countless lives and create shareholder value in the process.

Recent data suggest that roughly 15 million colorectal cancer screening tests are performed each year in the US, which is just a fraction of the nearly 100 million Americans who under the current guidelines should be screened.

Exact Sciences has developed an advanced, affordable and patient-friendly means of detecting colorectal cancer and pre-cancerous polyps.  In fact, it is the only non-invasive way to reliably detect pre-cancers. Unlike colonoscopy, the Exact test requires no bowel preparation or medication restrictions. Patients will be able to use our test in the comfort and privacy of their own homes. There is no need for sedation or missed days of work. Access to the test will be virtually unlimited, as sample collection kits could be distributed to patients and returned to the laboratory by mail.

The Exact Sciences test is designed to detect altered DNA from pre-cancer and cancer, leading to early diagnosis and in many cases the actual prevention of colorectal cancer. By performing our test at regular intervals, most pre-cancers could be detected before cancer develops. As with the Pap smear test, which has nearly eliminated cervical cancer among those regularly screened, it is our ultimate goal to eradicate colorectal cancer with regular and widespread application of an effective and user-friendly screening tool.

We believe the market opportunity in the US alone is more than $1bn annually. This assumes only 30 percent of people over age 50 will receive one test every third year. We own exclusive rights to this test, which we fully expect will detect more than 85 percent of cancers and more than 50 percent of pre-cancers. There is no other test in molecular diagnostics that has as great a market potential as this one.

Currently, Exact Sciences is making tremendous progress toward bringing this test to patients.  Our scientists have been working in close collaboration with doctors at Mayo Clinic in Rochester, MN. In July, Exact Sciences released tissue data that showed using our unique combination of four methylated biomarkers we could detect 100 percent of both colorectal cancers and pre-cancers with 100 percent specificity.

We are unaware of any other markers or combination of markers that has achieved such complete discrimination. The early validation began this fall and we plan to begin our multi-site clinical trial in the second quarter of 2011 with a goal of submission to the Food and Drug Administration in 2012.

We plan to launch the product shortly after FDA approval. Exact Sciences is working with the Centers for Medicaid and Medicare Service to secure coverage of our test upon FDA approval. We are laying the groundwork to commercialise our test. There remain several significant tasks to complete before our test is launched, and these will be carefully planned and executed. The company has engaged key physicians, laboratorians, and payers.

These leaders continue to provide us with valuable insight into the market and how they expect it to change. We are coupling these important perceptions with a thorough review of several cancer screening success stories in our industry, including Digene and Cytyc.

Investors and analysts have been responding favourably to our focus and the preliminary scientific data we have been able to provide regarding our assay.  Piper Jaffray initiated coverage of Exact Sciences in June with an overweight rating.

“Our overweight rating reflects expectations for management’s successful execution of Exact’s next-generation colorectal cancer screening assay commercialisation strategy and we expect investors will be rewarded as near-term milestones are realied,” wrote Piper Jaffray Senior Research Analyst William Quirk. Four other analysts have also initiated coverage of Exact Sciences, each one listing the company as a buy for investors.

I am confident that Exact Sciences is on the right path toward successfully developing and marketing a non-invasive patient-friendly colon cancer screening test. And my confidence grows each time I speak with members of the Exact Sciences team, who have in a short time proven that they have the intellect, desire and commitment to achieve our plan. Working together, we can achieve our goal of reducing colorectal cancer incidence and mortality in the US and around the world.

Research into the effects of psychedelics, used in the past in psychiatry, has been restricted in recent decades because of the negative connotations of drugs, but the scientists said more studies into their clinical potential were now justified.

The researchers said recent brain imaging studies show that psychedelics such as lysergic acid diethylamide (LSD), ketamine and psilocybin – the psychoactive component in recreational drugs known as magic mushrooms – act on the brain in ways that could help reduce symptoms of various psychiatric disorders.

The drugs could be used as a kind of catalyst, the scientists said, helping patients to alter their perception of problems or pain levels and then work with behavioural therapists or psychotherapists to tackle them in new ways.

“Psychedelics can give patients a new perspective – particularly when things like suppressed memories come up – and then they can work with that experience,” said Franz Vollenweider of the Neuropsychopharmacology and brain imaging unit at Zurich’s University Hospital of Psychiatry, who published a paper on the issue in Nature Neuroscience journal.

Depending on the type of person taking the drug, the dose and the situation, psychedelics can have a wide range of effects, experts say, from feelings of boundlessness and bliss at one end of the spectrum to anxiety-inducing feelings of loss of control and panic at the other.

Low doses
Vollenweider and his colleague Michael Kometer, who also worked on the paper, said evidence from previous studies suggests such drugs might help ease mental health problems by acting on the brain circuits and neurotransmitter systems that are known to be altered in people with depression and anxiety.

But if doctors were to use them to treat psychiatric patients in future, it would be important to keep doses of the drugs low, and ensure they were given over a relatively short time period in combination with therapy sessions, they said.

“The idea is that it would be very limited, maybe several sessions over a few months, not a long-term thing like other types of medication,” Vollenweider said in a phone interview.

A small study published by US scientists found that an infusion of ketamine – an anaesthetic used legally in both human and veterinary medicine, but also abused by people who use it recreationally – can lift the mood within minutes in patients with severe bipolar depression.

Mental illnesses such as depression are a growing health problem around the world and Vollenweider and Kometer said many patients with severe or chronic psychiatric problems fail to respond to medicines like the widely-prescribed selective serotonin reuptake inhibitors, or SSRIs, like Prozac or Paxil.

“These are serious, debilitating, life-shortening illnesses, and as the currently available treatments have high failure rates, psychedelics might offer alternative treatment strategies that could improve the well-being of patients and the associated economic burden on patients and society,” they wrote.

Researchers said the find may help doctors to give more personalised care to transplant patients and to modify the amount of powerful immunosuppressant drugs they have to take to prevent their bodies from rejecting a new kidney.

The scientists, led by Maria Hernandez-Fuentes at King’s College London, studied various groups of kidney transplant patients in Europe, including 11 patients who had stopped taking their drugs after the transplant but did not reject the donor organ since they appeared to have a natural “tolerance” for it.

They carried out detailed tests of blood samples and found differences in the immune systems particular to these patients.

“We hope that now we can start to look at screening other patients to see if they also have similar markers in their blood,” said Rachel Hilton, a renal consultant at Guy’s Hospital in London and co-author of the study.

“There may be many more patients out there who potentially could reduce or stop their medication if we can screen them to see if their immune systems looks similar,” she said in a telephone interview.

Kidney transplants are the most common type of major organ transplant worldwide – around 1,550 are carried out in Britain and around 18,000 in the US every year. The average lifespan of a transplanted kidney is 12 years, rising to around 20 years in some cases if the kidney is from a living donor.

For many patients, a kidney transplant opens up a new life, but it also means they must take immunosuppressants – which have a wide-range of side effects – for the rest of their lives to make sure the new organ is not rejected.

Novartis’s Neoral, Myfortic and Sandimmune, Roche’s Cellcept, Pfizer’s Rapamune and Prograf from Astellas Pharma are among some of the leading branded drugs given to prevent transplanted organ rejection.

“If you’re on these transplant drugs for life, then you have the side effects for life as well as the benefits,” said Hilton.

“The main side effects are increased risk of infection and a higher risk of future cancers, so they are very undesirable side effects in both the short- and the long-term.”

The European team compared the 11 patients who had a natural tolerance of the new kidney against patients who were taking varying amounts of immunosuppressants, as well as patients who were taking the drugs but also showing signs of rejecting the donor organ, and a group of healthy volunteers.

They described what they found what as a “full set” of markers which made “tolerance fingerprint” in some patients.

The findings were later corroborated in another study by the Immune Tolerance Network in the US and both studies were published by the Journal of Clinical Investigation.

But the findings do not mean transplant patients should stop taking their medication without talking to a doctor.

“It is vitally important..that transplant recipients do not stop taking their immunosuppression on the back of these research findings,” Hilton said. “Any reduction in medication needs to be very carefully managed and clinically monitored.”

Franco Cappuccio, head of the WHO’s collaborating centre for nutrition, said voluntary moves by the food industry had brought some progress, but lawmakers should now harness the scientific evidence on salt and seek to change the tastes of nations.

“There is now a total acceptance that salt is bad for us, we eat far too much of it, and it should be reduced,” Cappuccio told reporters in an interview.

“So there is great scope now to consider a regulatory approach to reinforce and sustain the voluntary moves.”

But Cappuccio, a professor of cardiovascular medicine at Warwick University, where the WHO’s nutrition centre is based, said powerful lobbying from the food and drink industry, whose profits are swelled by added salt, have slowed efforts to bring consumption levels down.

Cutting salt intake substantially reduces blood pressure, helping to lower the risk of heart attacks and strokes. High blood pressure is ranked as the the world’s number one killer, accounting for 7.5 million deaths a year.

A 2007 study which analysed all the available evidence at the time found that reducing salt intake around the world by 15 percent could prevent almost nine million deaths by 2015.

Another study in March found that cutting salt intake by just 10 percent in the US could prevent hundreds of thousands of heart attacks and strokes over decades and save the government $32bn in healthcare costs.

There is little doubt that we eat too much salt. In Britain, average adult intake is around 8.6 grams per day, while in the US it is around 10 grams, almost twice the amount suggested by the WHO.

Even the WHO recommendation of five grams a day is far more than we actually need, which is only around 1.5 grams.

Profits swelled by salt
“Most of the salt eaten in the western world – in fact around 80 percent of it – comes from salt added to food from food manufacturers, and only around 20 percent comes from the salt cellar or the salt we use in cooking,” Cappuccio said.

“In terms of consumer freedom we have effectively no choice. At the end of the day, multinationals feed most of the world.”

Food manufacturers use salt to enhance the flavour of food that might otherwise be tasteless, to increase thirst and then seek to quench it with fizzy drinks, and also to boost profits from meat products, which are injected with a solution of salted water to plump them up and add weight.

In the worst cases, Cappuccio said, injected salt water makes up as much as 30 percent of the weight of a product like a chicken breast fillet.

“That 30 percent is pure profit [for the manufacturer],” he said. “We need to start a programme of reformulation of food items. But that’s the really tricky part, because that requires the food industry coming on board.”

But he pointed to some positive steps.

In the US, the New York City Health Department is leading a “National Salt Reduction Initiative”, bringing cities, states and health organisations together to work with food manufacturers and restaurants to try to reduce Americans’ salt intake by 20 percent over five years.

In Britain, it is partly due to public health campaigns and the efforts of the Food Standards Agency (FSA) to work with food makers to cut salt and give clearer labelling that intake levels have come down to 8.6 grams per day average from around 10 grams a day around 10 years ago.

“We know from scientific studies that if you reduce your salt intake by a little amount every day or every week or every month…then you can retrain your taste buds,” Cappuccio said.

“So we really can retrain people – whole populations – to enjoy food with less salt in it.”

The researchers found a new gene called New Delhi metallo-beta-lactamase, or NDM-1, in patients in Asia and in Britain. NDM-1 makes bacteria highly resistant to almost all antibiotics, including the most powerful class called carbapenems.

With international travel for healthcare on the rise, the scientists said they feared this new superbug could soon spread around the world.

In a study published in The Lancet Infectious Diseases journal, the researchers found that NDM-1 is becoming more common in Bangladesh, India, and Pakistan and is starting to be imported back to Britain in patients returning from these countries.

“India also provides cosmetic surgery for other Europeans and Americans, and it is likely NDM-1 will spread worldwide,” the scientists, led by Timothy Walsh from Britain’s Cardiff University, wrote in a report of their findings.

Multi drug-resistant bacteria are already a growing problem in hospitals across the world, marked by the rise of “superbug” infections like methicillin-resistant Staphyloccus aureus (MRSA).

Walsh and his international team collected bacteria samples from hospital patients in two places in India, Chennai and Haryana, and from patients referred to Britain’s national reference laboratory between 2007 and 2009.

They found 44 NDM-1-positive bacteria in Chennai, 26 in Haryana, 37 in Britain, and 73 in other sites in Bangladesh, India, and Pakistan.

Several of the British NDM-1 positive patients had recently travelled to India or Pakistan for hospital treatment, including cosmetic surgery, they said.

Most worryingly, NDM-1-producing bacteria are resistant to many antibiotics including carbapenems, the scientists said, a class of the drugs generally reserved for emergency use and to treat diseases caused by other multi-resistant bacteria such as MRSA and C-Difficile.

Experts commenting on Walsh’s findings said it was important to be alert to the new bug and start screening for it early.

“If this emerging public health threat is ignored, sooner or later the medical community could be confronted with carbapenem-resistant (bacteria) that cause common infections, resulting in treatment failures with substantial increases in healthcare costs,” Johann Pitout from the University of Calgary in Canada wrote in a commentary in the same journal.

They identified a piece of the virus that appears to be the same even among mutated strains, and found a way to make it into a vaccine.

Years of work lie ahead but if it works in people the way it worked in mice, the new vaccine might transform the way people are now immunised against influenza, the team at the Mount Sinai School of Medicine in New York reported.

“We now report progress toward the goal of an influenza virus vaccine which would protect against multiple strains,” Dr. Peter Palese, Dr. Adolfo Garcia-Sastre and colleagues report in a new journal mBio.

“Current influenza vaccines are effective against only a narrow range of influenza virus strains. It is for this reason that new vaccines must be generated and administered each year.”

Flu viruses mutate constantly and each year a cocktail of three flu vaccines is tweaked to try and hit the most common new mutations. Every few decades a new pandemic strain emerges – a year ago the new H1N1 swine flu strain started a pandemic and it has been added to the seasonal flu vaccine mix.

It takes months to make a new flu vaccine and governments and commercial drug companies struggled to get the new H1N1 vaccine out by last September. Having a universal flu vaccine could, in theory, prevent future pandemics and keep seasonal flu under better control.

Vulnerable neck

Palese’s team focused on an important piece of the flu virus called hemagglutinin. This mushroom-shaped structure helps the virus attach to the cells it infects and gives flu viruses the “H” in their names.

The “neck” of hemagglutinin does not mutate the way more visible bits of the virus do, and if there was an easy way to help the immune system to see it, this provides a good antigen – a target for a vaccine.

But the top, umbrella-shaped part of the hemagglutinin protein hides this vulnerable neck from the immune system. Palese’s team found a way to get to the neck, cut it out and make a vaccine out of it.

“A headless hemagglutinin molecule could form the basis for a broadly protective influenza virus vaccine,” the researchers wrote.

“This paper is more proof of concept,” Garcia-Sastre said in a telephone interview. “We don’t think we have yet the most optimal way to display the antigen.”

Tests in mice showed the vaccine protected them from otherwise lethal doses of multiple strains of influenza.

Garcia-Sastre’s team made a plasmid, a circular piece of DNA, for their vaccine but other ways to do it include a virus-like particle, used in other vaccines, or bits of DNA made by a baculovirus, he said. He said they are open to working with a drug company on this.

Flu infects up to 10 to 15 percent of the US population each year, more in a pandemic year, and kills an estimated 36,000.

Dozens of companies make influenza vaccines and bring in millions of dollars in revenues from them. The US, for instance, bought 162 million doses of H1N1 vaccine from five makers – Novartis, AstraZeneca unit MedImmune, Sanofi Aventis, GlaxoSmithKline and Australian vaccine maker CSL.