About CheckOrphan

Founder and President of CheckOrphan.org

What lies beneath the surface: examining water-borne parasites

Water is essential for life on Earth. It is crucial for environmental and human health, necessary for food and energy security, and indispensable for continued urbanization and industry. One in nine people lacks access to safe water, but what does this mean?

We often think about getting sick from drinking unsafe water, but what lives in the water can also affect our health. For eight years, University of Alberta researcher Patrick Hanington has been studying parasites that infest water and affect human and animal health locally and internationally.

Hanington’s research focuses on schistosomiasis. It is one of the world’s widely neglected diseases, yet it is second only to malaria in terms of overall public health impact for parasitic diseases. The disease is caused by parasitic worms called schistosomes that live in specific species of freshwater snails. Infected snails release cercariae, the form of the parasite infectious to humans. When released, the cercariae look for a host and are attracted to human secretions. If people are in nearby water, the cercariae can penetrate through the skin, causing infection.

“In Canada, the schistosomes that lead to human disease are absent. However, similar parasites that naturally infect other animals can be found within resident snails. Cercariae released from these snails can encounter people in the water, causing what is commonly known as swimmer’s itch. The result is a temporary, itchy rash, which eventually goes away within two to five days,” says Hanington, assistant professor with the School of Public Health. “But in tropical, developing countries where good sanitation is often lacking, three species of schistosome exist that specify in infecting humans. These parasites lead to much more serious health complications.”

Intestinal schistosomiasis leads to liver and spleen enlargement, intestinal damage and hypertension. Urinary schistosomiasis leads to progressive damage to the bladder, ureters and kidneys. For women, this can also cause lesions in the urinary tract, meaning an infected individual has a greater risk for acquiring or transmitting HIV.

To further explore schistosomiasis internationally, Hanington is collaborating with William Anyan, a researcher at the Noguchi Memorial Institute for Medical Research at the University of Ghana. Together, they are building on their combined expertise in the snail stage of the schistosome life cycle. They plan to integrate their research with existing chemotherapy-based control programs in small rural communities in Ghana.

There, schistosomiasis infection rates are the third highest in Africa, ranging between 10 and 20 per cent prevalence and as high as 40 per cent in the south. In many of the smaller rural communities, infection rates are even higher, sometimes reaching 100 per cent of the children in a community. Often, everyday activities in these communities revolve around water.

“Local people are in the water every day, whether they are using it for fishing, cleaning, drinking, playing or bathing,” explains Hanington. “Avoiding interactions with water to prevent schistosomiasis is not reasonable. We’ve had to ask ourselves, ‘What can we do to work both with the community and with the environment to improve health and reduce the burden of schistosomiasis?'”

Hanington and his team are developing tools to estimate the risk of schistosome transmission from snails. They are also evaluating the snail and schistosome population structures. If they are able to understand the rate of transmission and how quickly the schistosomes are reinfecting both people and snails, then they will be better able to tailor control strategies to prevent new infections, avoid reinfection and assist those currently infected.

Ultimately, the objective is to complement drug administration programs by providing tools for measuring treatment effectiveness and reducing schistosome prevalence in both snails and people.

Hanington says that his research in Ghana has just scratched the surface, and he is looking forward to further discovery.

As part of ongoing efforts to build closer relationships with communities and researchers, Anyan was recently invited to the School of Public Health.
“Health knows no boundaries,” says Hanington. “The more we can collaborate on a common issue, exchange knowledge and assist one another, the more likely we are to have a significant health impact and alleviate human suffering.”

University of Alberta
Tel: (780) 492-0437

Author: Rachel Harper
Source: University of Alberta

Rett Syndrome Revelation

Scientists have known for 15 years that mutations in a single gene lead to Rett syndrome, a severe neurological disorder that affects girls around their first birthdays. In the years since the MECP2 gene was pinpointed, researchers have struggled to understand how it functions in the brain in Rett syndrome.

Now the enigma of Rett syndrome and perhaps other disorders on the autism spectrum could be one step closer to being solved.

A Harvard Medical School team has discovered that when MECP2 is mutated in Rett syndrome, the brain loses its ability to regulate genes that are unusually long. Their finding suggests new ways to consider reversing the intellectual and physical debilitation this disruption causes with a drug that could potentially target this error. The team, led by Michael Greenberg, reported its findings in Nature.

“The longer the gene, the more disrupted it becomes when you lose MECP2,” said Greenberg, the Nathan Marsh Pusey Professor of Neurobiology at HMS. “Rett syndrome may be a defect in this process of fine-tuning the expression of long genes.”

Scientists, including Greenberg, have figured out over the last 10 years that MECP2 plays a role in sculpting the connections between neurons in the developing brain. These synapses are refined by exposure to sensory experiences, just the sort of stimulation a one-year-old would encounter as she learns to walk and talk.

MECP2 is present in all cells in the body, but when the brain is forming and maturing its synapses in response to sensory input, MECP2 levels in the brain are almost 10 times as high as in other parts of the body. The new study connects MECP2 mutations to long genes, which may be more prone to errors simply because their length leaves more room for mistakes.
Speed Bump

“Normally, MECP2 may act like a speed bump, fine-tuning long genes by slowing down the machinery that transcribes long genes,” said Harrison Gabel, a postdoctoral fellow in the Greenberg lab and co-first author of the Nature paper. In transcription, the information in a strand of DNA is copied onto a new molecule of messenger RNA, which is then turned into a protein. “Without MECP2, the machinery may be moving too fast, making too much mRNA from these genes, resulting in problems for the neurons.”

Finding this effect of MECP2 on long genes was no small feat. In a typical search for the mechanism behind a genetic mutation, mice are engineered to lack the normal gene so that its absence reveals how it functions. However, work in many different labs has shown that knocking out MECP2 had only subtle effects when analyzed across the genome. The changes in gene expression were inconsistent, small and, using Gabel’s word, “fuzzy.”

Gabel took another approach, querying massive genomic databases such as ENCODE to ask a simple question: What do genes that are affected by mutated MECP2 have in common?

Answer: They are long. Most of them are at least five times longer than the average gene, with many of them more than 50 times longer than the average. It is important to note that the genes identified across dozens of data sets were very long, giving the researchers a common finding where previous conclusions from these data sets had lacked a common theme.

Harrison and co-first author Benyam Kinde, an MD-PhD student in the Greenberg lab, found the long-gene misregulation in multiple mouse models of Rett syndrome and confirmed it in the brain tissue of deceased Rett patients.

For MECP2 to function normally as a speed bump, it binds to a form of methylated DNA found in long genes in the brain. Methyl groups are chemical modifiers of gene activity, and in other parts of the body MECP2 binds methylated CG sites on genes. The methylation pattern that appears to be important for MECP2 in regulating long genes is known as methylated CA, and there appears to be a special mechanism operating as synapses are forming.

“It seems that evolution has used MECP2 and methylated CA to put in place this speed bump so that the expression of long genes is restrained in the brain,” Greenberg said. “As far as Rett syndrome, the thought is now that this subtle but widespread overexpression of long genes might be contributing to the disorder.”
Corrective Strategy

The scientists can’t be sure of what these overexpressed long genes do, but many of them appear to be very important to the function of the brain. This suggests that if they could correct the defect in long-gene expression, they might be able to reverse at least some of the symptoms of Rett syndrome. As a first attempt at a corrective strategy, the researchers selected a cancer drug called topotecan because it blocks an enzyme known to be important for long-gene transcription.

In a lab dish, they added topotecan to neurons lacking MECP2. The drug reversed the long-gene misregulation, suggesting that restoring normal long-gene expression might be a way to correct neurological dysfunction in Rett syndrome and in other autism spectrum disorders with long genes, such as fragile X syndrome. Topotecan, a chemotherapeutic agent, is too toxic, Greenberg said, but derivatives of topotecan might be a worthwhile avenue to pursue.

“We think this issue of long-gene misregulation may be more generally occurring in other disorders of human cognition,” Greenberg said. “The potential is pretty significant because one now has a common regulatory mechanism to target with drugs.”

This work was supported by grants from the Rett Syndrome Research Trust and the National Institutes of Health (1RO1NS048276 and T32GM007753), the Damon Runyon Cancer Research Foundation (DRG-2048-10), the William Randolf Hearst fund and the Howard Hughes Medical Institute

Source: Harvard Medical School

Study sheds light on how malaria parasites grow exponentially

A University of South Florida College of Public Health professor and his team of researchers have become the first to uncover part of the mysterious process by which malaria-related parasites spread at explosive and deadly rates inside humans and other animals.

As drug-resistant malaria threatens to become a major public health crisis, the findings could potentially lead to a powerful new treatment for malaria-caused illnesses that kill more than 600,000 people a year.

In a study published online March 3 in the high-impact journal PLOS Biology, the USF researchers and their colleagues at the University of Georgia discovered how these ancient parasites manage to replicate their chromosomes up to thousands of times before spinning off into daughter cells with perfect similitude – all the while avoiding cell death.

“How these parasites preserve fidelity in this seemingly chaotic process is one of the great mysteries of this pathogen family,” said USF Health’s Michael White, PhD, a professor in the Department of Global Health who partnered on the study with fellow USF researcher Elena Suvorova, PhD, in the USF Departments of Molecular Medicine & Global Health and the Florida Center for Drug Discovery and Innovation, as well as with two researchers from the University of Georgia.

In studying the malaria-relative Toxoplasma gondii, the team found an explanation for that puzzle.

To understand it, consider that malaria-related parasites are professional multipliers, unlike plant and animal species and single-cell organisms like yeast – where chromosomes get one shot at replication or else the cell dies or turns into cancer, Dr. White explained.

With malaria-related parasites, once transmitted into an animal or human, they can hide out in a single cell in many different tissues replicating silently tens, hundreds or even thousands of times before the host’s immune system can detect that they are there.

Then with the stealth of a Trojan horse, they burst forth as “daughter cells,” which are unleashed in massive quantities in waves, like a small army into the host’s system – quickly overwhelming a patient’s immune response, Dr. White explained.

What the study found was that the Toxoplasma parasites pull this off thanks to a “modified ‘control room’ called the centrosome that imposes order on the replication chaos,” Dr. White said. “Unlike the comparatively simple centrosome present in human cells, the parasite ‘control room’ has two distinct operating machines; one machine controls chromosome copying, while the other machine regulates when to form daughter cell bodies. Working together, but with independent responsibilities, parasite centrosome machines can dictate the scale and timing of pathogen replication.”

This groundbreaking understanding and novel discovery of the centrosome’s function leads to a critical conclusion: disruption of the centrosome machines – like cutting the cables between two computer systems – kills the parasite, Dr. White said.

Breaking any part of the highly efficient but highly fragile replication functions shuts everything down.

“They are literally Humpty Dumpty,” he added. “If they break, they can’t be put back together.”

With these findings and the new knowledge of the parasites’ vulnerabilities, Dr. White and his fellow researchers will delve into drug development.

That process could take anywhere from four to 10 years of further research and clinical trials before a new drug is on the market, he said. The length of time depends on whether the researchers hit upon effective application of prior-FDA approved cancer-related drugs or develop a new treatment from scratch.

Whatever treatment they develop, Dr. White stressed that it will be used in conjunction with other types of drug therapies.

Currently drugs used to treat malaria go after the pathogens’ metabolism, while the new research will seek to undermine the parasite’s foundation in enough of the spreading cells in order to allow the human immune system to fight back and not become overwhelmed, Dr. White said.

A major challenge today in parts of the world is the lack of access to drug treatments at all or until it is too late and the patient succumbs to malaria-related illnesses and brain hemorrhaging.

Because of the parasite’s high-adaptability, current drug treatments are constantly susceptible to the development of drug resistance, Dr. White said.

A potential global health crisis is unfolding as drug-resistant malaria continues to move across Burma, reaching the Indian border, according to British newspaper The Independent, commenting on a recent study in the journal Lancet. Doctors fear it will continue to spread and enter Africa, home to 90 percent of the world’s malaria cases.

Malaria caused about 207 million cases and 627,000 deaths in 2012, according to the Centers for Disease Control and Prevention. About 3.2 billion people, or half the world’s population, are at risk of malaria, according to the World Health Organization.

Dr. White said that this study, which he called the first for a USF Health laboratory in publishing original research in PLOS Biology, will help get more potential treatments in the pipeline.

“The more we understand their vulnerability,” he said of the parasites, “the better chance we can keep that pipeline full.”

The study was supported by a grant from the National Institute of Allergies and Infectioius Disease (NAID), National Institutes of Health.

“A Novel Bipartite Centrosome Coordinates the Apicoplexan Cell Cycle,” Elena S. Suvorova, Maria Francia, Boris Striepen and Michael W. White, PLOS Biology, March 3, 2015; DOI:10.1371/journal.pbio.1002093.

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit http://www.health.usf.edu


Anne DeLotto Baier
Tel: 813-974-3303

Catching Up With 3 Rare Disease Families

Four-year-old Eliza O’Neill’s viral videos, the subject of my last two blog posts, continue to dominate the news media with another appearance on The Today Show June 17. Hopefully, her family’s fight to fund gene therapy for her rare disease, Sanfilippo syndrome type A, will focus more attention on the entire rare disease community – 30 million people in the U.S. alone. That’s a lot of families. Four years ago, I spent the summer getting to know the families whose stories became my gene therapy book. Thanks to social media we’ve stayed in touch, and I’ve met many others. All continue to astonish me. Here’s a catch-up with three families featured in past posts. Laura King Edwards ran the Thunder Road half marathon blindfolded, in honor of her sister Taylor. Beside her is Dr. Steve Gray, PI of gene therapy trials for two brain diseases. RUNNING BLIND TO BATTLE BATTEN DISEASE Laura King Edwards posted at DNA Science a year ago about her younger sister Taylor, now 15, who was diagnosed with ceroid lipofuscinosis, neuronal type 1 – aka Batten disease – when she was 7. Recalls Laura: “In the worst hour of our lives, we learned that my bright-eyed, golden-haired, intelligent sister – a second grader who loved to sing and dance and run and play – would go blind, have seizures, and lose the ability to walk, talk, and swallow food. She would deteriorate … confined to a wheelchair. She would have to have a feeding tube. Eventually, she would die – blind, bedridden, and unable to communicate.” Laura eloquently captures her sister’s life and her family’s efforts to help fund a gene therapy clinical trial at her blog, Write the Happy Ending. A post from last week is particularly heartbreaking. Rather than charting her sister’s decline with brain scans or mobility tests, Laura notes that in the 6 weeks between haircuts, Taylor lost the ability to walk. Last week, she had to be carried up the stairs to the hairdresser. This week, she’s in the hospital. To better get into her sister’s head, Laura runs races blindfolded. “I do the runs for a variety of reasons. I’ve always been a runner, and running helped me face Taylor’s illness when she was first diagnosed. After watching her run the first of two 5Ks with her Girls on the Run team despite battling Batten disease (and she was already blind at that point), I started running in her honor. I mainly run for Taylor to raise awareness, but my runs have also raised money for Taylor’s Tale. The Thunder Road half marathon I ran with Dr. Steve Gray in November raised money for the (gene therapy) project at the University of North Carolina. I’ve run 18 races for Taylor. Thunder Road was the only race I ran blind, but I went on 18 blind training runs to get ready for it. 635205790291677074During my months of training to become a blind runner and far more so in the months following the race, my sister slipped farther down the chasm of Batten disease. It is a deep, dark chasm. There are no footholds for climbing out, and some days, no light reaches her ledge. And yet, each day she teaches me something new about courage; each day, she imparts some great piece of wisdom without having to say anything at all. My next challenge is to run a race in all 50 states for Taylor to continue spreading awareness of Batten disease and build support for the rare disease community. I’m kicking it off this summer!” HANNAH’S HOPE AND LOVE BALL Ten-year-old Hannah Sames also has a very rare inherited disease of the nervous system, giant axonal neuropathy (GAN). DNA Science told her story about a year ago too. In GAN, intermediate filaments composed of a protein called gigaxonin overgrow and run askew, hampering nerve function. Hannah is very slowly losing mobility, and suffers from kidney stones and visual loss, as the lack of gigaxonin in various body parts makes its presence known in ebbing motor and sensory functions. Dr. Gray (behind Laura in the photo above) began working on gene therapy for GAN before he took on the Batten disease project, and the GAN trial is set to begin within the next few months at the NIH Clinical Center. The trial is largely possible due to the constant networking, meeting-holding, and fundraising efforts of Hannah’s family – parents Lori and Matt, and sisters Reagan and Madison. Their Hannah’s Hope Fund (HHF) was born in the days following the diagnosis in 2008. The highlight is the annual ball, held in February in snowy Albany, NY, near the Sames (and my) home. From Lori: Doris Buffett's Sunshine Lady Foundation donated $500,000 in matching funds to Hannah's Hope Fund for GAN. “The Hope and Love Ball began 5 years ago when friends, Todd and Beth Silaika and Tim and Lee Wilson, approached us with the idea. The first formal gala in 2010 netted $90,000 and was a Valentine theme, fitting for February. Other themes followed: Monte Carlo, Mardi Gras, Midnight in Paris, and Candyland this year, which netted more than $165,000. In 2010, HHF was awarded a $500,000 all-or-nothing matching challenge grant from Doris Buffett’s Sunshine Lady Foundation. The deadline to raise the funds was the night of the Ball. Snow kept Ms. Buffett (Warren’s sister) away the evening when more than 450 HHF supporters celebrated the success of the $1.2 million, 6-month “Hope for a Million” fundraising campaign. Ms. Buffett was the highlight of the event the following year. To date, HHF has raised $6 million in 6 years, grassroots, with the vast majority of funds spent on the GAN gene delivery Investigational New Drug (IND) work. The FDA placed the protocol on “Active” status at the end of May, awaiting IRB approval of the GAN gene delivery system. Then trial recruitment can begin. Unfortunately, Hannah, the inspiration of HHF, has a homozygous deletion mutation. She isn’t a candidate for the phase 1 trial because only missense mutation patients will initially be included. Hannah is awaiting the results of a non-human primate study aimed at inducing tolerance to an intracellular transgene in the CNS. If tolerance is achieved, it will likely be 10 months to a year before Hannah can receive gene delivery.” (Hannah doesn’t make gigaxonin at all, and so introducing it into her spinal cord, via healthy genes in viral vectors, could trigger an explosive immune response. The other kids who will be in the trial make abnormal forms of the protein, and so their immune systems are already alerted that gigaxonin is a “self” protein.)

BIKE THE BASIN FOR CURING BLINDNESS Michael and Mitchell Smedley and their friends brainstormed the Bike the Basin event. A few months ago at DNA Science, Kristen Smedley told how she and her husband Mike assembled a research team to pursue gene therapy for the CRB1 form of Leber congenital amaurosis, which has robbed their sons Michael and Mitchell of sight. But the boys are more interested in having fun than recruiting researchers, so they dreamed up the hugely successful Bike the Basin event, a half-mile race at the Northampton Civic Center Basin in Bucks County, PA. Kristen continues. “Back in summer 2011 when the Curing Retinal Blindness Foundation launched, I asked my kids to come up with a fundraiser that could get their friends involved and start getting the word out about our big mission. I wanted my boys to take the lead because while it’s nice that so many people want to help them due to their blindness, my guys need to be able to show the world that they can help themselves. We gathered about 15 of their closest friends at my kitchen table and the boys pitched their idea of a bike event fundraiser. The kids brainstormed ideas of how to make it work (with parents taking notes and serving lots of ice cream) and Bike the Basin was born! Just under three months later, the first event raised $20,000. The first three BTB events raised just over $200,000 combined, and the goal for 2014 (Oct 5th) is $250,000. We’ve raised about $80K so far!” LOOKING AHEAD Hannah and her sisters and parents. The families who raise funds for gene therapy clinical trials begin with their own relatives in mind and perhaps as a way to channel their anxiety and fear into something productive. But their generosity extends much farther. As rare disease-based communities form and strengthen, certain individuals emerge as catalysts. Laura King Edwards, Lori Sames, and Kristen Smedley are three. Gene therapy will almost certainly be too late for Taylor, and possibly for Hannah. But the Smedley boys may one day be able to see. And Eliza O’Neill may find her way into a clinical trial before Sanfilippo syndrome darkens her sunny childhood, thanks to the efforts of the media to share her story, and the kindness of so many strangers. But Eliza is one child, representing one unicorn. There are so many more. Whatever the future holds, the efforts of these brave families will reverberate for years to come, measured in the numbers of lives improved or saved.

Irish Americans warned about Tay-Sachs disease striking community

The Irish American community is being warned about the risks and realities of Tay-Sachs disease, a fatal neurodegenerative disease for which an estimated one in 50 Irish and Irish Americans are carriers.

Tay-Sachs has a 25% chance of being passed on to children when both parents are carriers of an altered gene. Babies born with Tay-Sachs disease appear normal at birth, and symptoms of the disease do not appear until the infants are about four to six months of age when they begin to lose previously attained skills, such as sitting up or rolling over. Children then gradually lose their sight, hearing and swallowing abilities, and usually die by the age of five.

Currently, the only hope against Tay-Sachs is genetic screening. This is a common practice in the Ashkenazi Jewish community, where Tay-Sachs is prevalent. Because of this it was at one point believed to be a disease primarily affecting people of Jewish descent, but the volume of cases among those of Irish descent has proven that Tay-Sachs is found in groups where marrying within the community is common.

Two Philadelphia women – one Irish, one Jewish – have made it their mission to increase awareness about Tay-Sachs. Amybeth Weaver, a licensed genetic counselor with Einstein Healthcare Network, and Dr. Adele Schneider, head of the clinical genetics program at Einstein Medical Center, are campaigning fiercely to spread knowledge about Tay-Sachs within the Irish American community. All that is required for the screening is a basic blood test.

In a further effort, two mothers from the Philadelphia area recently spoke out about their heartbreaking experiences with Tay-Sachs.

In an interview with Mainline Today, Nancy Donegan and Eileen Kenny spoke about their experiences with Tay-Sachs. Donegan’s daughter Stefanie, was diagnosed 26 years ago at the age of two. By three-and-a-half she had lost the ability to walk and was put on a feeding tube. She lived to be eight, spending the last three years of her life in a vegetative state. Donegan recalled how her daughter “suffered unbelievably. I miss her every day.”

Kenny’s son Danny, now three years old, was diagnosed when he was just six months old. He lost the ability to walk at the age of two. Today, he no longer has control over his limbs and facial muscles. He has lost the ability to swallow, with his parents now responsible for suctioning the saliva out of his mouth. Kenny explained, “Danny used to babble, but he doesn’t anymore… He doesn’t laugh; he doesn’t cry; he doesn’t smile. He’s 3 years old, and he doesn’t make any noise. He’s just quiet.”

Though their children’s diagnoses came almost three decades apart, Donegan and Kenny were equally unaware of the risks of Tay-Sachs. Donegan is of Irish, English, French Canadian, and Italian heritage, and her ex-husband was of Irish descent. Kenny is a first-generation Irish American on both sides of her family and her husband had Irish grandparents on one side. Neither of them had any idea they could be carriers of Tay-Sachs. This is why they are helping to spread awareness.

“I can’t imagine life without Danny. He gives us love, and we love him. But Tay-Sachs disease is a horrible thing. It’s devastating to watch him suffer,” Kenny said.

In order to gather more accurate data on Tay-Sachs among people of Irish descent, Weaver and Dr. Schneider are conducting the Irish Tay-Sachs Carrier Study, through which they offer free genetic testing to people with at least three grandparents of Irish descent. The study is a joint project of Einstein and the National Tay-Sachs & Allied Diseases Association of Delaware Valley.


Amybeth Weaver
Tel: (484) 636-4197(484) 636-4197

Author: By Casey Egan
Source: Irish Central

A New Indiegogo Campaign

On Tuesday 17th February we will be launching a new crowdfunding campaign on Indiegogo! In 2013 we raised over $100,000 thanks to your generosity and support. In this week’s blog we explain why it is time for another campaign. In just 6 days time we will be launching a new crowdfunding campaign. As many of you will know, our last campaign was to raise money for the launch of an international clinical trial testing a promising drug called nitisinone. This trial is now well underway. We have completed recruitment, with over 135 patients taking part, and our doctors and scientists are pleased with the progress so far. This time we need your help to raise money to research the best age for patients to begin treatment.

Why the New Campaign? As you all know, AKU is a genetic disease, meaning it is with patients through their whole lives. From an early age urine is a dark colour, staining nappies. Unfortunately, symptoms get more serious with time. Patients develop crippling back and joint pain, resulting in many having to give up work. Older patients may need serious operations to replace or fuse their broken joints. If given at the correct age, nitisinone could prevent all the debilitating impacts of this disease. At the moment, the clinical trial is for adults only. This is because our scientists are worried there may be side effects if the drug is given at too young an age. However, the damage caused by AKU could be starting on a microscopic level from birth. Our research teams still don’t know exactly how the disease changes over a patient’s lifetime. Our SOFIA study will recruit patients from across Europe. Our researchers will compare patients in different age groups to assess when damage really begins. They will do this using a variety of tools, from assessing how patients walk, to taking blood, urine and ear cartilage samples. This research is very important- if we give the drug early enough, we may be able to prevent patients from ever experiencing any of the painful symptoms of AKU.

We Need Your Support Our new campaign, ‘Help us Cure Black Bone Disease: Time is Running Out’, will launch next week, on Tuesday 17th February. To make this campaign a success we need your support! But how can you help?

Sign up to our Thunderclap now

      Everyone who signs up to the Thunderclap will send out an automatic tweet or Facebook post simultaneously on the day of our campaign launch, spreading awareness over social media.

 You can sign up here Spread the word. 

      When our campaign launches, spread the word to your friends, and promote it over social media.

Send us your story. 

      Our capaign is all about helping patients, so we want you to get involved. If you would like to write an update for us about your experience living with AKU, please send it tosorsha@akusociety.org.

Fundraise and donate. 

      We are aiming to raise $30,000 (about £20,000) to support this important research. If you can help us meet this target by fundraising in your local area and donating, we would love to hear from you.

Last Time Last time we were overwhelmed by your support. The original Cure Black Bone Disease campaign exceeded our funding expectations, raising in total $121,012 from 1,470 donors. Your money is helping patients in three key ways. Firstly we have been able to run identification campaigns across Europe, helping us find many new patients. This gave patients the opportunity to take part in the trial, and helped us recruit enough patients to make the trial a success. Much of the money is also being spent on patient and carer travel. Many patients are unable to travel alone, and need to have a carer with them. We wanted to ensure there was always enough money to make this possible, improving the patient experience. One of the most important uses of money has been for patient support. This trial is for the benefit of patients, and we want patients to feel supported every step of the way. We ensure we have continuous contact with patients, before, during, and between visits to make sure they always have someone to speak to about concerns or worries.

Your Money This time your money will be used in a similar way. We want patients to be fully informed about the study, and be able to take part no matter what their circumstances, or where in Europe they live. Please help us to make this important research a reality by supporting our campaign when it launches on Tuesday 17th February.

If you have any questions about the campaign, you can get in contact with Sorsha by emailing sorsha@akusociety.org.

Plant extract fights brain tumor

Cushing Disease, not to be confused with Cushing’s Syndrome, is caused by a tumour in the pituitary gland in the brain. The tumour secrets increased amounts of the stress hormone adrenocorticotropin (ACTH) followed by cortisol release from the adrenal glands leading to rapid weight gain, elevated blood pressure and muscular weakness. Patients are prone to osteoporosis, infections and may show cognitive dysfunction or even depression. In 80 to 85 % of the patients the tumour can be removed by uncomfortable brain surgery. For inoperable cases, there is currently only one targeted therapy approved which unfortunately causes intense side effects such as hyperglycemia in more than 20 % of the patients.

Scientists around Günter Stalla, endocrinologist at the Max Planck Institute of Psychiatry in Munich, now discovered in cell cultures, animal models and human tumour tissue that a harmless plant extract can be applied to treat Cushing Disease. “Silibinin is the major active constituent of milk thistle seeds. It has an outstanding safety profile in humans and is already used for the treatment of liver disease and poisoning,” explains Marcelo Paez-Pereda, leading scientist of the current study published in the renowned scientific journal Nature Medicine. After silibinin treatment, tumour cells resumed normal ACTH production, tumour growth slowed down and symptoms of Cushing Disease disappeared in mice.

In 2013, the Max Planck scientists filed a patent on a broad family of chemical and natural compounds, including silibinin, to treat pituitary tumours. Compared to humans, of which only 5.5 in 100,000 people worldwide develop Cushing Disease, this condition is very common in several pets. For example, 4 % of dogs and even 7 % of horses suffer from Cushing Disease. Thus, the researchers now plan to test special formulations with a very pure substance and slow release of the active component silibinin in clinical trials.

Silibinin: Mode of action

“We knew that Cushing Disease is caused by the release of too much ACTH. So we asked ourselves what causes this over production and how to stop it,” says Paez-Pereda. In their first experiments the researchers found tremendously high amounts of the heat shock protein 90 (HSP90) in tumour tissue from patients with Cushing Disease. In normal amounts HSP90 helps to correctly fold another protein, the glucocorticoid receptor which in turn inhibits the production of ACTH. “As there are too many HSP90 molecules in the tumour tissue, they stick to the glucocorticoid receptor,” explains Paez-Pereda. “We found that silibinin binds to HSP90 thus allowing glucocorticoid receptor molecules to dissolve from HSP90. With silibinin we might have discovered a non-invasive treatment strategy not only for the rare Cushing Disease but also for other conditions with the involvement of glucocorticoid receptors such as lung tumours, acute lymphoblastic leukaemia or multiple myeloma,” concludes Paez-Pereda.

Riebold M, Kozany C, Freiburger L, Sattler M, Buchfelder M, Hausch F, Stalla GK and Paez-Pereda M. A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease. Nature Medicine, 9 February 2015


Marcelo Paez-Pereda
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