Waving White Flag, Celladon Merges With Rare Disease Co. Eiger Bio

Xconomy San Diego — A slew of companies have gone public amidst gene therapy’s recent renaissance, and technological advances have gotten these types of treatments closer than they’ve ever been to impacting healthcare in the U.S.

But today, Celladon offered a reminder of how quickly it can all go wrong in gene therapy. The San Diego biotech and its once promising treatment for a genetic form of heart failure will now effectively disappear, thanks to a merger with a privately held company called Eiger BioPharmaceuticals.

Celladon (NASDAQ: CLDN) has agreed to a deal with Eiger that, if approved by shareholders, would see Eiger’s stockholders become the majority owners of the combined company. The entity would carry forward the Eiger name, and the Palto Alto, CA-based company’s strategic plan to develop treatments for a variety of rare diseases like lymphedema, pulmonary arterial hypertension, and hepatitis D. All of Celladon’s directors and executives will resign from their current positions once the deal is done. The new company will be run by Eiger’s team, which is lead by president and CEO David Cory, and be based in the Bay Area.

This is the type of deal that often happens after a publicly held biotech waves the white flag. In January, for instance, Regado Biosciences of Basking Ridge, NJ, merged with Tobira Therapeutics after safety concerns doomed its potential anticoagulant drug. The combined company is known as Tobira, is one third owned by Regado’s old shareholders, and is now developing drugs for inflammatory and liver diseases. A few years ago, a pain drug developer called Zalicus failed a big trial, and merged with a biosimilars company called Epirus Biopharmaceuticals. Targacept, after a string of clinical failures, merged with Catalyst Biosciences in August. These deals give shareholders of the failed biotech a chance to recoup some value after things go wrong—and a quick way for a private company to tap into the public markets.

Now here’s Celladon, which was a high-flying gene therapy company not too long ago. For those unfamiliar, gene therapy is a way of shuttling genetic instructions into the body via a virus, offering the potential for a long-lasting or even permanent fix for a genetic disease. That promise has tantalized scientists for decades, but as with any new science, the field has gone through a number of ups and downs trying to figure out the best way to safely and effectively deliver these treatments.

The progress of companies like UniQure (NASDAQ: QURE), which has the only approved gene therapy in the world, Spark Therapeutics (NASDAQ: ONCE), which could become the first to win FDA approval of a gene therapy next year, and Bluebird Bio (NASDAQ: BLUE)—not to mention academic groups pursuing treatments for hemophilia and other diseases—has helped bring gene therapy back from the depths. A number of gene therapy companies have gone public over the past few years, and Celladon was one of them. It had the financial support of a number of corporate venture arms, like Pfizer Ventures and Novartis Venture Funds, became the first company to win a “breakthrough therapy” designation from the FDA for a gene therapy, and raised $44 million in an IPO in January 2014.

But despite the progress, there have been some setbacks in gene therapy as well, and Celladon unfortunately became one of the prime examples. Its gene therapy, Mydicar, a proposed treatment for patients with severe heart failure, failed miserably in a mid-stage study in April. Shares immediately plummeted 80 percent, and Celladon was forced to begin layoffs and search for strategic alternatives. Celladon’s shares had closed as high as $27.26 apiece in March, leading up to the data release. They’ve been worth just over $1 over the past several months during the trial fallout.

Those shares roughly doubled this morning following the announcement of the Eiger deal. Through it, a syndicate of investors new to Eiger—RA Capital Management, Sabby Management, Sphera Global Healthcare, Perceptive Advisors, and Monashee Capital Partners—-has teamed with longtime Eiger backers ViVo Capital and InterWest Partners to put $39.5 million into the new company. Eiger will have over $60 million in cash after the merger is completed, though the deal has to be approved by Celladon’s shareholders first. The cash should be enough to get Eiger through Phase 2 trials for at least two of its four programs by late 2016.

The company’s lead drug, lonafarnib (Sarasar), was originally developed by Schering Plough (now owned by Merck) and tested for a variety of cancers. Eiger licensed the drug from Merck, and is now developing it as a treatment for hepatitis D.

Celladon will issue about 85 million new shares to Eiger shareholders and the investors providing the financing. That’ll leave the new syndicate with 33 percent of the company, Eiger stockholders with 45 percent, and current Celladon equity holders with 22 percent.

Less effective antimalarial therapies can help fight malaria better

Oxford University scientists have found that the more effective way to beat malaria is to use less effective drugs some of the time.

The current drug of choice for malaria – artemisinin – is extremely effective at saving lives from the disease, but artemisinin-resistant malaria parasites are spreading as the drug is used more and more. A computer simulation study now suggests that treating malaria in a population by simultaneously using a non-artemisinin therapy amongst more effective artemisinin-based combinations is the best way to combat the disease, while still reducing the spread of drug-resistant malaria. Writing in the Lancet Global Health, scientists at the Nuffield Department of Clinical Medicine at Oxford University found that this combination worked best even when the non-artemisinin drug was only effective 85% of the time in treating malaria.

Currently, to stop the spread of artemisinin-resistant parasites, the World Health Organization (WHO) encourages the use of the drug in combination with other anti-malarials; the malaria parasite would have to become simultaneously resistant to both the drugs in order to survive this two-hit artemisinin combination therapy.

However, malaria parasites in South-East Asia have begun to acquire characteristics to help evade even this double hit, and these resistant strains are likely to spread over the next decade as the use of artemisinin combination therapies becomes more widespread.

Health policy makers are therefore in bind, having to decide whether to safeguard artemisinin effectiveness (by avoiding its overuse), or to encourage the use of artemisinin wherever possible to save people’s lives.

Professor Maciej Boni and his colleagues ran computer simulations to find out if there was an optimal strategy that could stop the spread of drug-resistant malaria parasites across populations, while still effectively treating malaria in individual patients. They found that simultaneously dosing a population with several artemisinin-combination therapies – say, by prescribing artemisinin in combination with different partner drugs on different days of the week – was more effective than either cycling between different artemisinin combination therapies, or by sticking to one specific combination until the combination started failing.

The simulation also found that if this simultaneous dosing also included a combination without artemisinin, malaria parasites that were resistant to artemisinin were slower to emerge, and slower to spread. Including this potentially less effective treatment option didn’t necessarily mean that many more people would not recover from malaria: in the worst case scenario of the non-artemisinin treatment being only 75% as effective as artemisinin combination therapy, fewer than 7% of malaria patients would still have post-treatment malaria parasites in their blood as a result of not being prescribed an artemisinin drug.

Professor Boni said, ‘For this subgroup of patients, second-line treatment with an artemisinin combination therapy would be recommended. The ethical implications of such a treatment policy will need to weighed against the benefit of delaying and slowing down the spread of artemisinin resistance.

‘But the nightmare we all want to avoid is the establishment of artemisinin resistance in Africa, where hundreds of millions of individuals rely on artemisinin-based therapies as their first-line antimalarial treatment. By deploying different antimalarial therapies simultaneously – including non-artemisinin-based therapies – national malaria control programs in Africa should be able to slow down the spread of artemisinin-resistant parasites when they are imported into the continent.’

Tom Calver

Top 10 Costliest Medical Drugs in the World

Top 10 Costliest Medical Drugs in the World

There are some of the pharmaceutical drugs that are very costly and are used to cure some of the rare diseases that may happen to the human beings. There drugs are so much expensive that it requires a very large amount of money if you are in a need of these drugs for medication purpose. We hope that no one requires these drugs ever. So here is the list of the top ten costliest drugs in the world.

10. Aldurazyme

Aldurazyme Top 10 Costliest Medical Drugs in the World

Our list starts with the drug Aldurazyme which is at the number tenth spot in our list of the top ten costliest drugs in the world. The name of the company that produces this drug is Genzyme and BioMarin Pharmaceutical. The annual cost of this life saving drug is 200,000 US dollars. This drug is also named as the Laronidase. This drug was approved in May 2003 for sale in different parts of the world. This pharmaceutical drug is used for the treatment of Mucopolysaccharidosi I. This medicine is given to the patients who has age between 5 & 65 and suffer with the Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I.

9. Cerezyme

Cerezyme Top 10 Costliest Medical Drugs in the World

The next pharmaceutical drug in our list is named as Cerezyme. To get this life saving drug one will have to pay 200,000 US dollar annually. This drug is manufactured by the pharmaceutical company named as Genzyme. The main ingredient of this drug  is Imiglucerase and it was first approved by the FDA on 23rd May 1994 and from then on the commercial sale of this drug got started.  This medicine is used for the treatment of a disease which is named as Gaucher. This medicine is actually the recombinant DNA which is produced as the analogue of human glucocerebrosidase. This medicine is sold in the market in the bottles of 200 units/vial and 400 units/vial.

8. Fabrazyme 

Fabrazyme Top 10 Costliest Medical Drugs in the World

Fabrazyme is the next drug in our list of the top ten costliest drugs in the world. This drug is manufactured by the pharmaceutical company named as Genzyme. The man ingredient of this drug is Agalsidase Beta. This drug was approved by the FDA for sale in the market on 24th April 2003. This drug which is one of the costliest in the market is used for the treatment of the disease called as Fabry. This drug is available in the form of injections of 35mg and 5mg. It is also sold in the form of Vial which are of 35mg/vial and 5mg/vial.

7. Arcalyst

Arcalyst Top 10 Costliest Medical Drugs in the World

The next medicine which is costliest in the world and is in our list is named as Arcalyst. This drug is manufactured by the pharmaceutical company named as Renege Pharmaceuticals. The other names of this drug are Rilonacept and IL-1 Trap. This medicine is used for the treatment of disease named as the Cryopyrin and its associated periodic syndromes. And also for the treatment of Muckle-Wells syndrome, familial cold autoinflammatory syndrome and neonatal onset multisystem inflammatory disease. If you are in need of this drug then you will have to pay 250,000 US dollars per year which is too much for a common man. This drug has been named as the Orphan Drug by the United States Food and Drug Administration. This drug was approved by the FDA on 8th May 2012.

6. Myozyme

Myozyme Top 10 Costliest Medical Drugs in the World

Myozyme is the next drug that we have in our list of the top ten costliest drugs in the world. The scientific name of this life saving drug is Alglucosidase alfa. Again Genzyme is the pharmaceutical company that manufactures this drug for sale in different parts of the world. This drug is actually an enzyme replacement therapy orphan drug which is used by the people who suffer from a deadly disease named as Pompe. Pompe is a disease which causes the rare lysosomal storage disorder. This drug is a type of substitute given to the human body so as to compensate the deficiency of enzyme which causes Pompe. For this drug you will have to pay 300,000 US dollars per year.

5. Cinryze

Cinryze Top 10 Costliest Medical Drugs in the World

Cinryze is the next drug in our list of the top ten costliest drugs in the world. For this drug one will have to pay 350,000 US dollars per year which is too much. This drug is manufactured by the pharmaceutical companies named as ViroPharma and Lev Pharmaceutical. This life saving drug was approved by the FDA in October 2008 and since then it is available in the market for sale. This drug is used in case of angioedema attacks in adolescents and also for the adults with Hereditary Angioedema. The area where this drug affects is the immune system and the paediatrics. For this drug one has to pay 350,000 US dollars every year.

4. Folotyn

Folotyn Top 10 Costliest Medical Drugs in the World

Pralatrexate is the drug that we have at the number forth spot in our list of the top ten costliest drugs in the world. This drug is sold by the brand name if Folotyn all over the world. If you are in a need of this drug then you will have to pay 360,000 US dollars annually. This is a drug which is used in the anti-cancer therapy. This drug is also used for the treatment of the refractory peripheral T-cell lymphoma disease. This drug was approved by the United States Food and Drug Administration in September 2009 and since then the commercial sale of this drug started.

3. Naglazyme

Naglazyme Top 10 Costliest Medical Drugs in the World

Naglazyme is the drug that we have at the number third spot in our list. This drug is manufactured by the BioMarin Pharmaceutical named company. For this drug one will have to pay 365,000 US dollars per year and so it becomes the third costliest drug in the whole world. The FDA approved this drug in May 2005 for sale in various parts of the world. This drug is used for the treatment of a disease named as Mucopolysaccharidosis VI and it affects the musculoskeletal part of the human body. This drug is also used for the Maroteaux-Lamy syndrome condition that may happen in any human beings.

2. Elaprase

Elaprase Top 10 Costliest Medical Drugs in the World

Idursulfase is the costliest drug that we have at the number second spot in our list. This drug is sold throughout the world by the brand name of Elaprase. For this life saving drug one will have to pay 375,000 US dollars per year. This drug is manufactured by the pharmaceutical company named as Shire Pharmaceuticals. This drug is used for the treatment of the disease named as Hunter syndrome which is also known as the Mucopolysaccharoidosis II.

1. Soliris

Soliris Top 10 Costliest Medical Drugs in the World

The costliest drug which is manufactured in any part of the world is undoubtedly Soliris. Eculizumab is the actual name of this life saving drug and it is traded by the name of Soliris throughout the world. This drug is actually a monoclonal antibody which is directed against the protein named as C5. This drug is manufactured by the pharmaceutical company named as Alexion Pharmaceuticals. If you are in need of this drug then you will have to pay 409,500 US dollars every year which is far more than any other drug in the whole world. This drug helps in the treatment of diseases such as hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria.

Huntington’s Patients Often Also Suffer from Psychiatric Disorders

Psychiatric manifestations develop more often than previously thought in Huntington’s disease prodrome, according to findings of a recent study published in The American Journal of Psychiatry. Moreover, it appears that symptoms also increase with disease severity.

Early features of Huntington’s disease can include personality changes, mood swings, fidgety movements, irritability and altered behavior, although these are often overlooked and attributed to something else. To better understand the progression and longitudinal course of psychiatric symptoms in patients carrying the Huntington’s disease mutation, in the study entitled “Longitudinal Psychiatric Symptoms in Prodromal Huntington’s Disease: A Decade of Data,” Dr. Jane Paulsen, from the Departments of Psychiatry and Neurology, Carver College of Medicine, University of Iowa, and colleagues used longitudinal assessment measures for up to 10 years of psychiatric indicators from the Symptom Checklist–90–Revised (SLC-90-R) in 1,305 participants (1,007 patients carrying the Huntington’s disease mutation, 298 controls without it; 1,235 companions were also assessed).

Participants were part of the longitudinal Neurobiological Predictors of Huntington’s Disease study (PREDICT-HD), which was conducted in 33 research sites across six countries (the United Kingdom, Canada, the United States, Germany, Australia and Spain). Eligible participants were tested for the Huntington’s disease gene mutation, and those who carried it were categorized into three clusters according to likelihood of motor diagnosis within five years.

The team examined the differences in psychiatric symptoms at baseline and over time between the mutation-positive groups and the controls, with the results demonstrating that 19 of 24 psychiatric assessments were higher at baseline and revealed a longitudinal increase in patients carrying the Huntington’s disease mutation when compared to controls.

“The results reported here provide initial information regarding psychiatric symptoms that occur in individuals who will develop Huntington’s disease and the importance of obtaining assessments from companions. This is critical to consider in future studies that assess behavioral manifestations and psychiatric symptoms, including those that investigate their underlying pathophysiology in Huntington’s disease and in therapeutic trials, as well as clinical assessment and management of persons who will develop Huntington’s disease,” the researchers concluded.

Rise of the Microglia

Microglia, the immune cells of the brain, have long been the underdogs of the glia world, passed over for other, flashier cousins, such as astrocytes. Although microglia are best known for being the brain’s primary defenders, scientists now realize that they play a role in the developing brain and may also be implicated in developmental and neurodegenerative disorders. The change in attitude is clear, as evidenced by the buzz around this topic at this year’s Society for Neuroscience (SfN) conference, which took place from October 17 to 21 in Chicago, where scientists discussed their role in both health and disease.

Activated in the diseased brain, microglia find injured neurons and strip away the synapses, the connections between them. These cells make up around 10 percent of all the cells in the brain and appear during early development. For decades scientists focused on them as immune cells and thought that they were quiet and passive in the absence of an outside invader. That all changed in 2005, when experimenters found that microglia were actually the fastest-moving structures in a healthy adult brain. Later discoveries revealed that their branches were reaching out to surrounding neurons and contacting synapses. These findings suggested that these cellular scavengers were involved in functions beyond disease.

The Brain’s Sculptors
The discovery that microglia were active in the healthy brain jump-started the exploration into their underlying mechanisms: Why do these cells hang around synapses? And what are they doing?

During early development, the brain starts off with many more synapses than it needs. Then, through pruning, these networks are refined. Microglia are critical to this process: they gobble up synapses, thus helping to sculpt the brain by eliminating unwanted connections. But how do microglia know which synapses to get rid of and which to leave alone?

New evidence suggests that a protective tag that keeps healthy cells from being eaten by the body’s immune system may also shield against microglial activity in the brain. Emily Lehrman, a doctoral candidate in neuroscientist Beth Stevens’s laboratory at Boston’s Children’s Hospital, presented these unpublished findings at this year’s SfN. The researchers found that this protective tag is highly expressed in the visual system in mice at five days after birth, when synaptic pruning peaks. Removing this protective tag in mice led to excess engulfment by microglia and overpruning of neuronal connections.

But pruning is not always a bad thing. Other molecules work to ensure that microglia remove weak connections, which can be detrimental to brain function. Cornelius Gross, a neuroscientist at the European Molecular Biology Laboratory, and his research group have been investigating the activity of fractalkine, a key molecule in neuron-microglia signaling whose receptors are found exclusively on microglia. “Microglia mature in a way that matches synaptogenesis, which sets up the hypothesis that neurons are calling out to microglia during this period,” Gross says.

His lab found that removing the receptor for fractalkine created an overabundance of weak synaptic contacts caused by deficient synaptic pruning during development in the hippocampus, a brain area involved in learning and memory. These pruning problems led to decreased functional connectivity in the brain, impaired social interactions and increased repetitive behavior—all telltale signs of autism. Published last year in Nature Neuroscience (Scientific American is part of Springer Nature), this work was also presented at the conference.

When Pruning Goes Awry
Studies have also found evidence for increased microglial activation in individuals with schizophrenia and autism; however, whether increased microglial activity is a cause or effect of these diseases is unclear. “We still need to understand whether pruning defects are contributing to these developmental disorders,” Stevens says.

Some findings are emerging from studies on Rett syndrome, a rare form of autism that affects only girls. Dorothy Schafer, now at the University of Massachusetts Medical School, studied microglia’s role in Rett syndrome while she was a postdoctoral researcher in Stevens’s lab. Using mice with mutations in MECP2, the predominant cause of the disease, she found that while microglia were not engulfing synapses during early development, the phagocytic capacity (or the gobbling ability) of these cells increased during the late stages of the disease. These unpublished results suggest that microglia were responding secondarily to a sick environment and partially resolve a debate going on about what microglia do in Rett syndrome—in recent years some studies have shown that microglia can arrest the pathology of disease, whereas others have indicated that they cannot. “Microglia are doing something, but in our research, it seems to be a secondary effect,” Shafer says. “What’s going on is still a huge mystery.”

Return of the Pruning Shears
As the resident immune cells, microglia act as sentinels, sensing and removing disturbances in the brain. When the brain is exposed to injury or disease, microglia surround the damaged areas and eat up the remains of dying cells. In Alzheimer’s disease, for example, microglia are often found near the sites of beta-amyloid deposits, the toxic clumps of misfolded proteins that appear in the brain of affected people. On one hand, microglia may delay the progression of disease by clearing cellular debris. But it is also possible that they are contributing to disease.

Early synapse loss is a hallmark of many neurodegenerative disorders. Growing evidence points to the possibility that microglial pruning pathways seen in early development may be reactivated later in life, leading to disease. Unpublished data from Stevens’s lab presented at the conference suggest that microglia are involved in the early stages of Alzheimer’s and that blocking microglia’s effects could reduce the synapse loss seen in Huntington’s disease.

As a newly burgeoning field, there are still more questions than answers. Next year’s conference is likely to bring us closer to understanding what these dynamic cells are doing in the brain. Once the underdogs, microglia may be the key to future therapeutics for a wide variety of psychiatric and neurodegenerative disorders.

Laughing through the pain: A comedy writer’s experience with chronic illness

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, on a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from a Los Angeles woman with Ehlers-Danlos Syndrome.

woman laughing2When you fall down at least once a week, you learn to laugh it off. No matter how much it hurts, you laugh because you know it makes other people more comfortable with what’s going on. If they believe you’re all right, your story is a comedy rather than a tragedy. I’m quite sure that this lesson I learned as a child (and have called on hundreds of times since) had a big part in my decision to become a comedy writer and performer, a career I began a decade before I was finally diagnosed with Ehlers-Danlos Syndrome.

Everyone with my rare connective tissue disorder knows the routine of explaining our condition to others. I like to gauge at what point a healthy person’s eyes glaze over and they check out completely; it’s usually around when I get to my issues that are caused by EDS, like arthritis and gastroparesis. After my first few monotonous rundowns of what ails me failed to enthrall anyone, I began weaving elements of humor into my explanations: “I have hip dysplasia, so I can’t be in the Westminster dog show… My joints hyperextend, which is great for sex but terrible for JV soccer… I tore my hamstring in Greece, but it’s not like that’s the worst thing that ever happened there.” Once engaged, people are much more likely to find some aspect of my condition that interests them and ask about that. This type of light interaction is far more comfortable than feeling like I’m teaching an NIH seminar on some disease nobody cares about.

In my experience, the people who really appreciate someone with a sense of humor are those I rely on most: Doctors and nurses. Just after my diagnosis, I was so confused and in so much pain that I was relatively curt with medical professionals. I also thought that if I even smiled, they would think I was faking my illness. But once my symptoms started to improve a bit and I understood more about what was happening, I tried being open and jovial with those who were treating me. The result was great; it should not have come as a surprise that a doctor who likes his patient is more likely to pay attention to her. Regardless of how badly I feel or how much I think something devastating may be happening to my body, I now try my hardest to make whatever dumb jokes I can manage in the hospital or at the doctor’s office. The staff members, many of whom somehow make it through day after day of maudlin events and miserable people, respond quite positively to my Tommy Boy quotes and ridiculous metaphors about how the exam room smells like a robot dog’s pee. (In fact, I would like to think I get better treatment because of David Spade.)

The need to laugh off my issues has become so innate that it is now my first response when I go into shock. My old roommate loves to tell the story of when I stepped onto our back porch and it looked like a sniper hit me: I was down in an instant. She ran out to see what was wrong and found me laughing hysterically, screaming, “I’m fine! Everything’s fine!” When I saw her worried, maternal expression, it made me even more afraid; I knew I had to alleviate her concern for both of our sakes, so I kept up my laughing and made jokes even as the unbelievable pain set in. As it turns out, I had ruptured my Achilles tendon and torn my calf muscle so badly that the orthopedic surgeon said it looked “like pulled pork; like a zipper went down the whole thing from top to bottom.” Looking back, I laughed and joked to make my roommate think everything was fine – the way you would treat a toddler who fell down and looks to you to gauge the severity of his injuries – but really I was the toddler, and making myself laugh got me through it.

I do not know where my life would be without my love of comedy, nor how I would have made it through the ups and downs of Ehlers-Danlos Syndrome. When it comes to relating to people, passing time in the hospital, or just convincing ourselves that there’s a lighter side to almost every situation, the most important part of the human body is the funny bone.

Paula Dixon is a comedy writer and photographer based in Los Angeles. She is a graduate of the USC School of Cinematic Arts and the Spéos Institute of Photography in Paris. She will be returning soon with her humorous podcast The Chronic Life, which covers chronic illness as well as pop culture and personal revelations.

Photo by bruna camargo

Genes linked with malaria’s virulence shared by apes, humans

The malaria parasite molecules associated with severe disease and death–those that allow the parasite to escape recognition by the immune system–have been shown to share key gene segments with chimp and gorilla malaria parasites, which are separated by several millions of years, according to a new study led by Harvard T.H. Chan School of Public Health. This new information about the origin and genetics of human malaria virulence factors could aid in basic understanding of the causes of malaria and provide targets for drugs and vaccines.

The study will be published online October 12, 2015 in Nature Communications.

“The evolution of these key virulence determinants doesn’t occur in the same way as in other pathogens. Instead of gradually changing by mutation, like the flu virus, these malaria parasites exchange intact gene segments, like shuffling a deck of cards,” said Caroline Buckee, assistant professor of epidemiology at Harvard Chan School and senior author of the study.

Malaria kills more than 500,000 people a year, mostly children in Sub-Saharan Africa. Severe disease syndromes in human malaria–including severe malarial anemia, pregnancy-associated malaria, and cerebral malaria–have been linked with the malaria parasite’s ability to cause infected red blood cells to bind to the inner lining of blood vessels. This ability of the infected cells to adhere in this way–which is key to malaria‘s virulence–is linked with certain genes called var genes.

Looking at hundreds of var sequence fragments using network analysis, the researchers discovered that short segments of these genes are shared across many different malaria parasites affecting humans, apes, and chimps. These segments are not recent adaptations, but rather reflect an ancient genomic structure.

“Astonishingly, we have found the very same shared sequence mosaics in these highly divergent species, implying that these short mosaic sequences, in spite of continual diversification, have an ancient origin,” Buckee said. “The origin of human malaria virulence factors is actually much older than previously thought.”

Lead author of the study was Daniel B. Larremore, former postdoctoral fellow in the Center for Communicable Disease Dynamics at Harvard Chan School and now an Omidyar fellow at the Santa Fe Institute.

Funding for the study came from the National Institutes of Health (R21 GM100207, R01 AI091595, R37 AI050529, R01 AI058715, T32 AI007532 and P30 AI045008) and the Wellcome Trust (grant #090851).

“Ape parasite origins of human malaria virulence genes,” Daniel B. Larremore, Sesh A. Sundararaman, Weimin Liu, William R. Proto, Aaron Clauset, Dorothy E. Loy, Sheri Speede, Lindsey J. Plenderleith, Paul M. Sharp, Beatrice H. Hahn, Julian C. Rayner, and Caroline O. Buckee, Nature Communications, October 12, 2015, doi: 10.1038/ncomms9368

Visit the Harvard Chan website for the latest news, press releases, and multimedia offerings.

Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people’s lives–not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America’s oldest professional training program in public health.


Marge Dwyer