Penn Medicine Launches First Apple ResearchKit App for Sarcoidosis Patients

App combines patient resources with research

Penn Medicine today launched its first Apple ResearchKit app, focused on patients with sarcoidosis, an inflammatory condition that can affect the lungs, skin, eyes, heart, brain, and other organs. The effort marks Penn’s first time using modules from Apple’s ResearchKit framework, as part of the institution’s focus on mobile health and innovative research strategies.

ResearchKit is an open source software framework designed specifically for medical research that helps doctors and scientists gather data more frequently and more accurately from participants using an iPhone. Since its launch two years ago, valuable data collected from the iPhones of patients with Parkinson’s disease, breast cancer, and asthma who opt in to use these applications, has poured into medical centers investigating better ways to study and treat these diseases.

Developed by Misha Rosenbach, MD, an assistant professor of Dermatology in the Perelman School of Medicine at the University of Pennsylvania, and Daniel O’Connor, a fourth-year Penn medical student, in collaboration with Marc Judson, MD, at Albany Medical College as well as the Foundation for Sarcoidosis Research, the app will deliver informational resources to patients, supplying links to disease information and advocacy groups, and directing them to specialists in their area based on their phone’s GPS. Patients will have the ability to opt in to a research study which can provide researchers with a trove of data about this rare disease. Optional, once-a-month surveys will query users about, for example, their symptoms and flare ups, how sarcoidosis affects their lives, and medications. The app will also optionally pull data naturally tracked through sensors on iPhone – from the weather to physical activity – to help the researchers spot any trends.

Among potential queries the technology will allow investigators to explore: When sarcoidosis is flaring, are patients walking fewer steps? Do they miss work? Does their disease flare after a week’s worth of sunny days? Does geographic location affect symptoms? Is there a seasonal variability? How quickly do patients respond to treatments?

“There’s a great opportunity that has never been done,” Rosenbach said. “In traditional research, you can’t see patients every day, but in app-based research you can suddenly get all this information about the disease in real-time and over time, from many different patients all over the world. It gives us the power to do sarcoidosis research in a way that has never been done.”

One of the biggest challenges in medical research is numbers. Researchers are faced with a shortage of patients for clinical studies. Even in a more common research space like cancer, studies have shown only 3 to 5 percent of patients volunteer to participate. But it’s especially hard in rare disease research because of a much smaller pool of patients. Sarcoidosis, which occurs in the lungs for about 90 percent of patients, is diagnosed in anywhere between 10 to 30 out of 100,000 Americans each year. It can affect nearly anyone, but disproportionately affects African Americans, particularly black women.
The largest study to date, the ACCESS trial (A Case-Control Etiologic Sarcoidosis Study), enrolled about 800 patients over a three-year period across 20 medical centers in the United States, and still failed to completely answer many critical questions, Rosenbach said.
“This new app has the potential to build up a larger cohort of more diverse patients in a shorter amount of time,” he said. “There’s a motivated and engaged group of sarcoidosis patients who are active online, but there’s a whole host of them out there we don’t know about. This app, which can securely, privately, and anonymously collect data, casts a wide net that may engage those people, and funnel valuable, much-needed information to researchers.”

The exact cause of sarcoidosis is unclear, but many researchers agree it starts from an immune response to some foreign material trigger, such as an atypical infection. When the body encounters a foreign material that it can’t fight off, it builds up a protective wall of inflammatory cells called a granuloma – lumps of cells. In sarcoidosis patients, this production never shuts off – it keeps going and going, resulting in numerous granulomas – that can damage organs, particularly the lungs.

With this project, researchers will determine whether the app is an effective method of studying the disease and collecting quality of life measurements used in today’s conventional clinical studies. Survey questions to enrollees can be tweaked throughout the process, if necessary, as new data rolls in or input from health care leaders and the sarcoidosis community emerges.

Data gathered from the app, the researchers said, could impact how tomorrow’s clinical studies are designed.

“We’re excited about future opportunities to repurpose the app for other rare diseases, as well,” O’Connor said. “With a strong app framework in place, ‘sarcoidosis’ could be swapped out for another disease, allowing wide networks of patients all over the country to participate in Penn studies without traveling to Philadelphia.”

Battling Psoriasis: Can-Fite Advances to Critical Worldwide Phase III Clinical Trial

Psoriasis, a skin disorder expressed by dry, red reptile-like scales, is autoimmune, meaning cells in the body attack cells supposed to help put down the ailment. Several medicines exist, but not without effects that lead to more problems. In what amounts to a psoriasis coup, Can-Fite BioPharma found a way to clear skin and restore quality of life to those with this miserable disease, inciting no adverse consequences, and contained in a simple pill.

A fast journey, Can-Fite recently set its Phase III plan to use Piclidenoson, formerly CF101, in front of Europe’s EMA, our equivalent of FDA but quicker. EMA was receptive. The pivotal study will have all the proper scientific controls in place, where doctors don’t know if they’re handing out Piclidenoson or sugar pills.
Most important, planned global trials in 400 patients will pit Piclidenoson against the wildly-popular and lucrative Otezla (a blockbuster bringing in billions), from Celgene Corp. for psoriasis. Prior head-to-head studies against Otezla proved favorable and were subsequently published in highly-respected Journal of Drugs in Dermatology. As in the former study, Phase III will seek improvement versus placebo under medical-vetted psoriasis scoring as a first endpoint; the second will expect to show Piclidenoson equal to Otezla in efficacy.
Biologics for psoriasis are dangerous. Injectables operate to harness the immune system but fall short – side effects like respiratory illness are rampant, to name a few. Can-Fite’s drug works better. Two biochemical helpers – IL 17 and IL 23 are key. Can-Fite has found a way to employ these crucial players in the autoimmune disease of inflammation that represent different internal pathways than competitors.

Psoriasis affects millions worldwide – a medical market of $4 billion and growing exponentially. Can-Fite’s drug has shown safety and efficacy in 1,000 patients so far.
Piclidenoson brings information from cells of the body to enable certain functions in the body. How Piclidenoson works is elegant: it targets a biologically essential adenosine receptor to stop action that may result in disease, specifically autoimmune disorders where blood and organs attack themselves. Because Piclidenoson only works on ‘bad’ cells that cause inflammation, ‘healthy’ cells are spared; hence, the lack of detrimental side effects.

Inquiring about Can-Fite’s choice of receptor to study, I spoke to Pnina Fishman, CEO and founder of Can-Fite, who replied: “The reason we selected A3AR stems out of findings showing it is highly expressed on diseased cells but low expressed on normal cells. This makes it a specific target. This receptor doesn’t play a physiological role and is expressed when a disease evolves. So it does not mediate any adverse events”.

Two psoriasis pharma stars light up the medical sky – Celgene’s compound and another heavy-hitter from Johnson & Johnson, Stelara, which lists as bad side effects the risk of life-threatening allergic reactions, skin cancer, and blood leakage into the brain that may kill. Yet the drug is about to rake in $3 billion in 2016.
Piclidenoson works differently than Otezla, which is based on an asthma drug as I describe in an earlier article, and whose close biochemical cousin is used for erectile dysfunction. Otezla’s common side effects include unbearable migraine, diarrhea and vomiting and even thoughts of suicide, which led 6% of clinical trial patients to voluntarily stop treatment of the drug (see box below for a comprehensive list of psoriasis treatments).

By contrast, Piclidenoson may cause slight sinus trouble and earache, although occurring in a very low percentage of patients.

Gene therapy for blistering skin disease appears to enhance healing in clinical trial

Grafting sheets of a patient’s genetically corrected skin to open wounds caused by the blistering skin disease epidermolysis bullosa appears to be well-tolerated and improves wound healing, according to a phase-1 clinical trial conducted by researchers at the Stanford University School of Medicine.

The results mark the first time that skin-based gene therapy has been demonstrated to be safe and effective in patients.

The findings will be published Nov. 1 in JAMA. Associate professors of dermatology Peter Marinkovich, MD, and Jean Tang, MD, PhD, share senior authorship of the study. Senior scientist Zurab Siprashvili, PhD, is the lead author.

For the study, four adult patients with recessive dystrophic epidermolysis bullosa, an excruciatingly painful genetic skin disease, received the skin grafts.

“Our phase-1 trial shows the treatment appears safe, and we were fortunate to see some good clinical outcomes,” said Tang. “In some cases, wounds that had not healed for five years were successfully healed with the gene therapy. This is a huge improvement in the quality of life for these people.”

People with epidermolysis bullosa lack the ability to properly produce a protein called type-7 collagen that is needed to anchor the upper and lower layers of the skin together. As a result, the layers slide across one another upon the slightest friction, creating blisters and large open wounds. The most severe cases are fatal in infancy. Other patients with recessive dystrophic EB can live into their teens or early adulthood with supportive care. Often these patients die from squamous cell carcinoma that develops as a result of constant inflammation in response to ongoing wounding.

The Stanford researchers showed that it was possible to restore functional type-7 collagen protein expression in patient skin grafts to stop blistering and allow wounds to heal. They also found that the protein continued to be expressed and that wound healing was improved during a year of follow up.

Looking to build upon results

The researchers seek to build upon these promising early results in a new trial that will include patients ages 13 and older.

“Moving into the pediatric population may allow us to intervene before serious chronic wounds and scars appear,” said Marinkovich, who directs the Stanford Blistering Disease Clinic. Repeated rounds of wounding and scarring on the fingers and palms, for example, often lead to fusion of the skin and the formation of what’s known as a “mitten hand.”

Siprashvili used a virus to deliver a corrected version of the type-7 collagen gene into batches of each patient’s skin cells that had been harvested and grown in the laboratory. He coaxed these genetically corrected cells to form sheets of skin about the size of an iPhone 5. The sheets were then surgically grafted onto the patient’s chronic or new wounds in six locations.

The researchers tracked the status of the grafts at one-, three- and six-month intervals for at least a year, checking to see if they stayed in place and caused wound closure. They also looked for any evidence of an immune reaction to the grafts, and whether the grafts continued to make the corrected type-7 collagen protein.

All 24 grafts were well-tolerated, the researchers found. Furthermore, they could detect expression of the type-7 collagen protein in the correct location of the skin in nine out of 10 tissue biopsies at three months. After 12 months, they were able to detect the collagen protein in five out of 12 biopsies.

Wound healing

Similar results were seen with wound healing. After three months, 21 of the 24 grafts were intact. This number dropped to 12 out of 24 after one year.

“Even a small improvement in wound healing is a huge benefit to the overall health of these patients,” said Tang. “For example, it may reduce the likelihood of developing squamous cell carcinoma that often kills these patients in young adulthood.”

Coupling grafts with hand surgery to break up scarred, fused tissue could help patients maintain the use of their hands, Marinkovich said.

Tang, Marinkovich and their colleagues will continue to monitor the patients in the phase-1 trial throughout their lifetimes to assess any long-term effects of the grafts.

The completion of the phase-1 trial and the potential to improve upon these outcomes is due to a concerted, long-term effort at Stanford to find ways to help young patients with this devastating disease.

The researchers are now starting a phase-2 clinical trial and are looking for new patients. For more information, send an email to tangy@stanford.edu or mpm@stanford.edu.

“This trial represents the culmination of two decades of dedicated clinical and basic science research at Stanford that began with the arrival of the former dean of the School of Medicine, Eugene Bauer, who set up the multidisciplinary EB Center at Stanford,” said Tang. “We have been working for a long time to get to this potential therapy into patients. We had to discover the genes and proteins involved and the responsible mutations. We then had to learn to deliver the corrected gene and grow those cells into sheets suitable for grafting.”

“We could not have reached this point without the support of the EB patients and their families,” said Marinkovich. “Since the time of my research training in the laboratory of Robert Burgeson, PhD, who discovered type-7 collagen, I’ve been deeply motivated to contribute to the EB community, and it is very satisfying to be able to finally see this molecular therapy come to fruition.”

The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.