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

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

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
Tel: 49-893-062-2263

Smartphone, finger prick, 15 minutes, diagnosis — done!

A team of researchers, led by Samuel K. Sia, associate professor of biomedical engineering at Columbia Engineering, has developed a low-cost smartphone accessory that can perform a point-of-care test that simultaneously detects three infectious disease markers from a finger prick of blood in just 15 minutes. The device replicates, for the first time, all mechanical, optical, and electronic functions of a lab-based blood test. Specifically, it performs an enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy: all necessary power is drawn from the smartphone. It performs a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and non-treponemal antibody for active syphilis infection.

Sia’s innovative accessory or dongle, a small device that easily connects to a smartphone or computer, was recently piloted by health care workers in Rwanda who tested whole blood obtained via a finger prick from 96 patients who were enrolling into prevention-of-mother-to-child-transmission clinics or voluntary counseling and testing centers. The work is published February 4 in Science Translational Medicine. Sia collaborated with researchers from Columbia’s Mailman School of Public Health; the Institute of HIV Disease Prevention and Control, Rwanda Biomedical Center; Department of Pathology and Cell Biology, Columbia University Medical Center; Centers for Disease Control and Prevention–Laboratory Reference and Research Branch, Atlanta; and OPKO Diagnostics.

“Our work shows that a full laboratory-quality immunoassay can be run on a smartphone accessory,” says Sia. “Coupling microfluidics with recent advances in consumer electronics can make certain lab-based diagnostics accessible to almost any population with access to smartphones. This kind of capability can transform how health care services are delivered around the world.”

Sia’s team wanted to build upon their previous work in miniaturizing diagnostics hardware for rapid point-of-care diagnosis of HIV, syphilis, and other sexually transmitted diseases. “We know that early diagnosis and treatment in pregnant mothers can greatly reduce adverse consequences to both mothers and their babies,” Sia notes. The team developed the dongle to be small and light enough to fit into one hand, and to run assays on disposable plastic cassettes with pre-loaded reagents, where disease-specific zones provided an objective read-out, much like an ELISA assay. Sia estimates the dongle will have a manufacturing cost of $34, much lower than the $18,450 that typical ELISA equipment runs.

The team made two main innovations to the dongle to achieve low power consumption, a must in places that do not always have electricity 24/7. They eliminated the power-consuming electrical pump by using a “one-push vacuum,” where a user mechanically activates a negative-pressure chamber to move a sequence of reagents pre-stored on a cassette. The process is durable, requires little user training, and needs no maintenance or additional manufacturing. Sia’s team was able to implement a second innovation to remove the need for a battery by using the audio jack for transmitting power and for data transmission. And, because audio jacks are standardized among smartphones, the dongle can be attached to any compatible smart device (including iPhones and Android phones) in a plug-and-play manner.

During the field testing in Rwanda, health care workers were given 30 minutes of training, which included a user-friendly interface to aid the user through each test, step-by-step pictorial directions, built-in timers to alert the user to next steps, and records of test results for later review. The vast majority of patients (97%) said they would recommend the dongle because of its fast turn-around time, ability to offer results for multiple diseases, and simplicity of procedure.

“Our dongle presents new capabilities for a broad range of users, from health care providers to consumers,” Sia adds. “By increasing detection of syphilis infections, we might be able to reduce deaths by 10-fold. And for large-scale screening where the dongle’s high sensitivity with few false negatives is critical, we might be able to scale up HIV testing at the community level with immediate antiretroviral therapy that could nearly stop HIV transmissions and approach elimination of this devastating disease.”

“We are really excited about the next steps in bringing this product to the market in developing countries,” he continues. “And we are equally excited about exploring how this technology can benefit patients and consumers back home.”

The study was funded by Saving Lives at Birth transition grant (USAID, Gates Foundation, Government of Norway, Grand Challenges Canada, and the World Bank) and Wallace H. Coulter Foundation.


Holly Evarts
Tel: 347-453-7408

Twin girls both need liver transplants, but dad can only donate to one

A father from Ontario is facing impossible news: He’s a liver transplant match for his 3-year-old twins, both of whom suffer from the same life-threatening disease, but he can only donate his tissues to one of them.

The Canadian couple, Johanne and Michael Wagner, adopted the twins from Vietnam in 2012, knowing of the girls’ illness.

“We were willing to go through with the adoption, thinking at least we could give them the love of the family and be able to hold their hand until the very end,” Johanne told the CBC, a Canadian news organization.

The sisters, Binh and Phuoc, suffer from Alagille syndrome, a genetic disorder that causes irregularities in the liver that can lead to a dangerous build-up of bile that severely damages the organ. The disease is also associated with heart defects, kidney disease, and physical abnormalities, but the effects on the liver are often the most serious.

Because of the severity of the Wagner twins’ syndrome, drugs and other interventions are no longer helping—both girls need a liver transplant. The couple recently found out that Michael is a match for the girls, so he can be what’s called a “living donor.” These types of transplants are most commonly done with kidneys, but it’s possible with the liver (as well as the lungs and pancreas) because the organ can regenerate.

Sadly, though, in order for the surgery to be safe for him, surgeons can only remove a small part of his liver, and he can only do it once because of the way the tissue regenerates.

Doctors at Toronto General Hospital will make the final call as to which child will receive a portion of Michael’s liver, factoring in the severity of each girls’ condition.

“We told them we didn’t want to be burdened with the decision-making,” Joanne told The Globe and Mail. The first operation is expected to take place within the next few weeks.

While this is anything but easy for the parents, they are sharing their story to raise awareness about live donors and hoping that a liver soon becomes available for their second daughter. Joanne says they’ve already received hundreds of message from willing volunteers via a Facebook page the couple set up, ABC News reported. The Wagners are referring all who are interested to Toronto General Hospital to see if they’re a match.

Receiving a portion of a liver from a living donor comes with many benefits. It usually lasts longer than a liver from a deceased donor, and there is little to no waiting period—whereas there are nearly 17,000 people currently in the United States waiting for a liver transplant. To be a live donor you don’t necessarily have to be a family member of the recipient, but many hospitals want donors that share some sort of an emotional relationship.

The surgeries do not come without serious risks. For donors, complications like infections, blood clots, damage to surrounding tissue or organs, or even death are possible, according to the American Transplant Foundation. And recipients face the same, plus the small chance of rejection that comes with any transplant.

Still, Michael is willing to take it on, a true hero for his daughters’ health

Author: By Leslie Barri
Source: FOX NEWS