BIOMED Israel – May 20-22, 2014
Dr. Jules T. Mitchel, President of Target Health will again be attending the BioMed Conference in Israel. As part of a mini symposia on May 20, Dr Mitchel will be presenting on the topic of Repurposing/Reprocessing and 505(b)(2) Regulatory Pathway. BioMed is the time and place that we have the chance to meet with our many friends and colleagues in Israel and to update each other in face-to-face meetings. Let us know if you will be attending and we will find a time to have a coffee.
Springtime in NYC – Central Park ©Target Health
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Recycling Astronaut Urine for Energy and Drinking Water, Stem Cell Research and More
Astronaut Nicholas Patrick near the cupola module during a spacewalk.
On the less glamorous side of space exploration, there’s the more practical problem of waste — in particular, what to do with astronaut urine. But rather than ejecting it into space, scientists are developing a new technique that can turn this waste burden into a boon by converting it into fuel and much-needed drinking 1) ___. Their report could also inspire new ways to treat municipal wastewater. Eduardo Nicolau, Carlos R. Cabrera and colleagues point out that human waste on long-term journeys into space makes up about half of the mission’s total 2) ___. Recycling it is critical to keeping a clean environment for astronauts. And when onboard water supplies run low, treated urine can become a source of essential drinking water, which would otherwise have to be delivered from Earth at a tremendous 3) ___. Previous research has shown that a wastewater treatment process called forward osmosis in combination with a fuel cell, can generate power. Nicolau’s team decided to build on these initial findings to meet the challenges of dealing with urine in space. The team collected urine and shower wastewater and processed it using forward osmosis, a way to filter contaminants from urea, a major component of urine, and water. Their new Urea Bioreactor Electrochemical system (UBE) efficiently converted the urea into ammonia in its bioreactor, and then turned the 4) ___ into energy with its fuel cell. The system was designed with space missions in mind, but the results showed that the UBE system could be used in any wastewater treatment systems containing urea and/or ammonia, the researchers conclude.
Mayo Clinic researcher, Abba Zubair, M.D., Ph.D, believes that stem 5) ___ grown in the International Space Station (ISS) could help patients recover from a stroke, and that it may even be possible to generate human tissues and organs in space. He just needs a chance to demonstrate the possibility. The Center for the Advancement of Science in Space (CASIS), a nonprofit organization that promotes research aboard the ISS, has awarded Dr. Zubair a $300,000 grant to send human stem cells into space to see if they grow more rapidly than stem cells grown on 6) ___. Dr. Zubair, medical and scientific director of the Cell Therapy Laboratory at Mayo Clinic in Florida, says the experiment will be the first one Mayo Clinic has conducted in space and the first to use these human stem cells, which are found in 7) ___ marrow. On Earth, we face many challenges in trying to grow enough stem cells to treat patients, he says. It now takes a month to generate enough cells for a few patients. A clinical-grade laboratory in space could provide the answer we all have been seeking for regenerative medicine. Dr. Zubair specifically wants to expand the population of stem cells that will induce regeneration of neurons and 8) ___ vessels in patients who have suffered a hemorrhagic stroke, the kind of stroke which is caused by blood clot. Dr. Zubair already grows such cells in his Mayo Clinic laboratory using a large tissue culture and several incubators – but only at a snail’s pace.
Experiments on Earth using microgravity have shown that stem cells will grow faster, compared to conventionally grown cells. If you have a ready supply of these cells, you can treat almost any condition, and can theoretically regenerate entire 9) ___ using a scaffold, Dr. Zubair says. Additionally, they don’t need to come from individual patients ? anyone can use them without rejection. Dr. Zubair is working with engineers at the University of Colorado who are building the specialized cell bioreactor that will be taken to the ISS within a year for the experiment. I don’t really think growing cells in space for clinical use on Earth is science fiction, he says. Commercial flights to the ISS will start soon, and the cost of traveling there is coming down. We just need to show what can be achieved in 10) ___, and this award from CASIS helps us do that.
In terms of commercial flights, on April 20, 2014, the privately owned, SpaceX Dragon successfully berthed with the International Space Station, marking the fourth time that one of the company’s Dragon spacecraft has made the trip successfully. NASA and SpaceX are partnering with CASIS, to perform experiments that will help humankind, explore space and also, contribute new technology useful on Earth. The spacecraft made a series of several engine burns in the wee hours of the morning to make its approach. At around 7:14am EST, the space station’s robotic arm grappled onto the Dragon and brought it close to the station’s Harmony module. The arm was controlled by Japanese astronaut Koichi Wakata and NASA’s Rick Mastracchio. The Dragon craft was loaded with 5000 pounds of cargo for the space station. In addition to supplies for the astronauts, the spacecraft is also loaded with a number of scientific experiments, including a space garden and a smartphone powered satellite. (You can read more about the scientific experiments on board Dragon here.)
On board the Dragon spacecraft is the PhoneSat 2.5, a small CubeSat which is powered solely by the guts of a smartphone. A CubeSat is a type of miniaturized satellite for space research that usually has a volume of exactly one liter (10 cm cube), has a mass of no more than 1.33 kilograms, and typically uses commercial off-the-shelf components for its electronics. This is the fifth in a series of such satellites, which are launched from the space station’s CubeSat launcher. Given both the ubiquity and low cost of smartphones, the purpose of this series of experiments is to examine the ability to quickly produce satellites for unique and more interesting applications. NASA is using these pioneering small spacecraft missions to gauge the use of consumer-grade smartphone technology as the main control electronics of a capable, yet very low-cost, satellite. If NASA’s successful at re-purposing smartphones to use to power satellites, it could lead to more creative and interesting scientific experiments.
An Astronaut’s Garden
Image Credit: NASA
Coming along for the ride on the SpaceX Dragon is NASA’s Veg-01 experiment. This will involve studying the use of a plant growth facility that will be used to grow lettuce. The plant growth chamber (dubbed Veggie) was developed by the Wisconsin-based Orbital Technologies Corporation. If it’s successful, it could lead to a permanent plant growth chamber on the station. For the astronauts, that means a nice little garden where they can grow and actually eat some fresh food. Veggie will provide a new resource for U.S. astronauts and researchers as the capabilities are begun to develop the ability to grow fresh produce and other large plants on the space station.
CASIS Sponsored Biochemical Research
The Center for the Advancement of Science in Space (CASIS) has been the manager of the U.S. National Laboratory since 2011. It’s also been charged by NASA with finding and selecting the best scientific experiments to work with on the ISS. So they’ve been focusing on finding customers who have a sound need for 11) ___ exposure, according to CASIS’s COO Duane Ratliff. They ran their first set of experiments to the International Space Station in January on an Orbital Sciences launch. Today they’re launching several different experiments that could pay off in creating the drugs of tomorrow. That’s because microgravity environments offer some unique insights into chemistry and biology in a way that simply can’t happen in Earth’s gravity.
These experiments include observing the crystallization of antibodies to better understand their mechanism. A CalTech experiment will attempt to crystallize a protein involved in Huntington’s 12) ___. Also, Proctor and Gamble will be delivering drug mixtures to help determine how much of an active ingredient is actually necessary for the drug to be effective. In microgravity, the ingredient will be uniformly disbursed and scientists can see what the ultimate level needs to be for an effective product, explained Ratliff. If they can minimize key ingredient with the same usefulness, will lower price of that product. CASIS sponsored research is also expanding the frontier of space science because the Dragon spacecraft will allow for some equipment to be powered during the launch. That will allow for more delicate experiments to be transferred to the space station. According to Ratliff, It’s an interesting launch for us because it’s the first launch vehicle that provides a powered ride up. That provides a controlled environment for some of the sensitive environmental experiment. The docking wasn’t the only successful part of SpaceX’s launch. It was also making its first test of its Falcon 9’s reusable first stage – a step towards the company’s goal of a reusable rocket. According to SpaceX, the first stage of the rocket did successfully make the engine burns that allowed it to land safely in the Atlantic Ocean for recovery. That’s a big win for the company, since it gave this part of the mission a 30-40% chance of success.
And that part of the flight wasn’t the only success that SpaceX announced for its reusable rocket program this week. Earlier this week, the company tested its reusable Falcon 9 rocket on the ground in New Mexico. That flight had a successful lift off, the rocket then hovered for a few seconds at an altitude of 250m, then safely landed back on the ground.
ANSWERS: 1) water; 2) waste; 3) cost; 4) ammonia; 5) cells; 6) Earth; 7) bone; 8) blood; 9) organs; 10) space; 11) microgravity; 12) disease
Learn more from the following four videos:
Stem-cell research scheduled to take place aboard the International Space Station could lead to new cancer therapies, says Roland Kaunas, associate professor in the Department of Biomedical Engineering at TexasA&M University. Kaunas is part of a team preparing the cell culture for space travel in an effort to provide a new method for studying the impact of tumor cells on stem-cell differentiation into bone
Abba Zubair, M.D., Ph.D, medical and scientific director of the Cell Therapy Laboratory at Mayo Clinic inFlorida, talks about the $300,000 his research team has received from The Center for the Advancement of Science in Space grant, to send human stem cells into space to see if they grow more rapidly than stem cells grown on Earth.
On board the International Space Station, Expedition 38 Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency discussed the maintenance of crewmembers’ health in orbit and space medicine with students from various Japanese schools during an in-flight event on Jan. 21. Wakata, who has been aboard the complex since early November, will become the first Japanese commander of the station in March for the final two months of his six-month mission on the orbital laboratory.
Lift-off of SpaceX rocket, Dragon
The human body is a complex machine, perfectly adapted to life on Earth with its force of gravity and built-in protection from harmful space radiation. But what happens when we venture into a hostile environment like space?
Eduardo Nicolau, Jose J. Fonseca, Jose A. Rodr?guez-Mart?nez, Tra-My Justine Richardson, Michael Flynn, Kai Griebenow, Carlos R. Cabrera. Evaluation of a Urea Bioelectrochemical System for Wastewater Treatment Processes.
ACS Sustainable Chemistry & Engineering, 2014; 2 (4): 749 DOI: 10.1021/sc400342x; American Chemical Society. Recycling astronaut urine for energy and drinking water.
NASA Milestones in Space-Medical Research – Part 2
Inspired by the space suits Apollo astronauts wore to survive the moon’s harsh climate, the Recharge™ Active Cooling System by Cool Systems Inc. helps patients with multiple sclerosis and heat-related neurological disorders manage their symptoms by lowering their core body temperature. Photo courtesy of NASA
DIGITAL IMAGING BREAST BIOPSY SYSTEM
A non-surgical system developed with Space Telescope Technology that greatly reduces the time, cost, pain, and other effects associated with traditional surgical biopsies.
BREAST CANCER DETECTION
A solar cell sensor that determines exactly when x-ray film has been exposed to optimum density; it reduces exposure to radiation and doubles the number of patient exams per machine.
A depth sensor of damage, improving patient treatment and saving lives in serious burn cases.
HUMAN TISSUE STIMULATOR
A device employing NASA satellite technology that is implanted in the body to help control chronic pain and involuntary motion disorders through electrical stimulation of targeted nerve centers or particular areas of the brain.
Custom-made suit that circulates coolant to lower body temperature; it dramatically improves symptoms of multiple sclerosis, cerebral palsy, spina bifida, and other conditions.
An implant connected to a physician’s computer and used to regulate heart rate, incorporating multiple NASA technologies.
An image-processing technique developed by NASA and now used to detect eye problems in very young children. Cool type of laser, called an excimer laser, which offers precise non-surgical cleanings of clogged arteries and fewer complications than in balloon angioplasty.
ULTRASOUND SKIN DAMAGE ASESMENT
An advanced ultrasound instrument to immediately assess
VOICE-CONTROLLED WHEELCHAIR?Robotic wheelchair manipulator that responds to 35 one-word voice commands, helping patients to perform daily tasks like picking up packages, opening doors, and turning on appliances.
WATER PURIFICATION SYSTEM?A municipal water treatment system for developing nations that uses iodine instead of chlorine to kill harmful bacteria.
Medical training in zero gravity
NASA: Affects of microgravity on the human body
The Human Body in Space
The human body is uniquely designed to live in Earth’s gravity. In space, the body begins to adapt to the microgravity environment. NSBRI’s science and technology program is addressing ways to reduce or eliminate many of the changes to the body that impact an astronaut’s ability to perform well in space and that might impact their health after returning to Earth. The NSBRI program also looks at ways to enhance countermeasures already in place on long missions. Here’s a quick introduction to how the body reacts to life in space.
In microgravity, astronauts no longer walk to get to different parts of the spacecraft, they float. This means that the bones in the lower part of the body that typically bear weight – the legs, hips and spine – experience a significant decrease in load bearing. This reduction leads to bone breakdown and a release of calcium, which is reabsorbed by the body, leaving the bone more brittle and weak. The release of calcium can also increase the risk of kidney stone formation and bone fractures. To put it in perspective, postmenopausal women who are untreated for bone loss can lose 1-1.5% of bone mass in the hip in one year while an astronaut can lose the same amount of hip bone mass in a single month. On missions outside Earth’s orbit, radiation exposure may also impact bone loss.
Extended spaceflight results in less load on the leg muscles and on the back’s muscles used for posture. As a result, the muscles can begin to weaken or atrophy, and this could lead to fall-related injuries and accidents during exploration missions. Astronauts currently exercise to help maintain their muscle mass, but nutritional interventions designed to reduce the muscle loss may one day be added as a complement to the exercise program.
In space, the body no longer experiences the downward pull of gravity that distributes the blood and other body fluids to the lower part of the body, especially the legs. The fluids are redistributed to the upper part of the body and away from the lower extremities. While in space, astronauts often have a puffy face due to this fluid shift and legs that are smaller in circumference. The fluid shift to the head can also lead to a feeling of congestion.
Although the cardiovascular system generally functions well in space, the heart doesn’t have to work as hard in the microgravity environment. Over time, this could lead to deconditioning and a decrease in the size of the heart. There is also a concern that space radiation may affect endothelial cells, the lining of blood vessels, which might initiate or accelerate coronary heart disease.
The Spine: Taller in Space
Astronauts get a bit taller in space. On Earth, the disks between the vertebrae of the spinal column are slightly compressed due to gravity. In space, that compression is no longer present causing the disks to expand. The result: the spine lengthens, and the astronaut is taller. One possible side effect is back pain that may be associated with the lengthening of the spine.
Inner Ear and Balance System
On Earth, a complex, integrated set of neural circuits allows humans to maintain balance, stabilize vision and understand body orientation in terms of location and direction. The brain receives and interprets information from numerous sense organs, particularly in the eyes, inner ear vestibular organs and the deep senses from muscles and joints. In space, this pattern of information is changed. The inner ear, which is sensitive to gravity, no longer functions as designed. Early in the mission, astronauts can experience disorientation, space motion sickness and a loss of sense of direction. Upon return to Earth, they must readjust to Earth’s gravity and can experience problems standing up, stabilizing their gaze, walking and turning. These disturbances are more profound as the length of microgravity exposure increases. The changes can impact operational activities including approach and landing, docking, remote manipulation, extravehicular activity and post-landing normal and emergency egress.
Sleep and Performance
Many factors – the loss of a 24-hour day/light cycle, a confined environment and work demands – can impact an astronaut’s ability to work well in space. In addition, exploration crews will have to shift their body clocks from the Earth day/night cycle to that of their destination. Scientists hope to help the crew increase their alertness and reduce performance errors through improvements to spacecraft lighting, sleep schedules and the scheduling of work shifts
Here are a few examples of how medical research is improving life in space and on Earth
Noninvasive Sensor Measures Muscle Chemistry in Space
Trauma and acute medical problems, along with loss of muscle strength and endurance, are serious risks facing astronauts on long missions. A noninvasive sensor developed by Dr. Babs R. Soller is expected to reduce the crew’s set-up time for scientific studies which now require complex equipment to assess astronaut fitness in orbit. The sensor will also provide real-time feedback to astronauts on the effectiveness of their exercise routines to maintain their aerobic performance while in space. Prototype sensors underwent ground testing involving stationary cycling and treadmill walking/running at NASA Johnson Space Center. In the future, the sensor could be worn by astronauts in their spacesuits to monitor oxygen consumption during extravehicular activities to assure they do not exhaust life support capability when they are away from the spacecraft or exploration outpost.
Although the device is planned for use during routine exercise, all crew members would also be trained to use it in response to a medical emergency. The sensor provides needle-free determination of muscle oxygen and pH. Measurements of muscle oxygen levels can be used to gain early indication of undetected internal bleeding, and muscle pH levels would provide feedback on adequacy of therapy to address poor oxygen delivery resulting from bleeding or sepsis. These measurements can be used to provide an early indication of shock, assess its severity and help guide patient treatment.
Expanding Medical Care in Space with Ultrasound
Ultrasound provides powerful diagnostic capabilities. In space, diagnosis and management of health problems can be difficult due to limited medical training and experience. Developed by Dr. Scott A. Dulchavsky in collaboration with NASA and Wyle Integrated Science and Engineering, an ultrasound training program gives non-physician astronauts the tools to assess health using real-time remote assistance from medical experts. The team developed rapid training methods and CD Rom refresher modules that allow non-physicians to perform diagnostic quality ultrasound exams on the International Space Station (ISS).
Ultrasound can be used to assess fractured bones, collapsed lungs, kidney stones, organ damage, and tendon injury. Dr. Dulchavsky’s group is also developing an ultrasound imaging catalog system for medical diagnosis in space. The product includes predictive modeling capabilities. Dr. Dulchavsky has worked with flight surgeons and successive ISS crews to advance the project to a level for evaluation in spaceflight. Although the project is not yet completed, the results, compiled in collaboration with NASA and Wyle, have been embraced by NASA flight surgeons, who have adopted the technology for clinical, operational use.
PVT Self Test Advances to International Space Station (ISS)
Through his NSBRI grants, Dr. David F. Dinges used laboratory analog environments to gather data using a test that objectively measures processes involving attention, vigilance and reaction time. Participants completed a 3-minute Psychomotor Vigilance Test (PVT) Self Test. The test was developed through Dr. Dinges’ work with NSBRI, NASA, Department of Defense, National Institutes of Health, and Department of Homeland Security. PVT Self Test requires the user to watch for a visual signal and respond quickly and accurately when it appears. During four NASA Extreme Environment Mission Operations (NEEMO 9, 12, 13 and 14) missions and at Devon Island, PVT Self Test was performed at least four times a day – on waking, before and after simulated lunar activities, and before bed.
Astronaut feedback was solicited during development of an interface component to the test that provides users with immediate feedback. PVT Self Test was renamed “Reaction Self Test” as it advanced to a flight experiment on the International Space Station in 2009. The study will provide a validated measurement of in-flight cognitive performance and will help NASA characterize and quantify the risk of performance errors due to sleep loss, sleep schedule disruption, fatigue and work overload. The PVT Self Test is also being implemented in the Russian Mars 520-Day Mission Simulation. The study, started June 3, 2010, simulates a mission to Mars with a six-man international crew living in a mock-spaceship, isolation chamber in Moscow.
Oxytocin Promotes Social Behavior in Infant Rhesus Monkeys
Oxytocin, a hormone produced by the pituitary gland, is involved in labor and birth and in the production of breast milk. Studies have shown that oxytocin also plays a role in parental bonding, mating, and in social dynamics. Because of its possible involvement in social encounters, many researchers have suggested that oxytocin might be useful as a treatment for conditions affecting social behaviors, such as autism spectrum disorders. Although oxytocin has been shown to increase certain social behaviors in adults, before the current study it had not been shown to do so in primate infants of any species.
The study was published online in Proceedings of the National Academy of Sciences (28 April 2014), working with infant rhesus monkeys, NIH researchers have found that oxytocin increased two facial gestures associated with social interactions- one used by the monkeys themselves in certain social situations, the other in imitation of their human caregivers. The authors began by gauging the ability of rhesus macaques to imitate two facial gestures: lip smacking and tongue protrusion. In lip smacking, the lips are protruded and open, then smacked together repeatedly. Rhesus mothers will engage in this facial gesture with their infants in the first month after giving birth. Tongue protrusion involves a brief protrusion and retraction of the tongue. Although this gesture is seen in other primates and typically not seen in macaques, macaques will imitate it when their human caregivers display it.
By observing the monkeys’ ability to imitate the two gestures, the authors sought to determine if oxytocin could promote social interaction through a gesture that was natural to them as well as through a gesture not part of their normal communication sequence. The authors tested the infants in the first week after birth. Three times a day, every other day, the caregivers would demonstrate the facial gestures in sequence to the infant monkeys, while the animals’ responses were recorded on video. At this phase of the study, the authors found that some of the monkeys mimicked their caregivers’ gestures more frequently than did other monkeys. The authors referred to the monkeys who gestured more frequently as strong imitators.
Beginning in the second week of life, the authors tested the monkeys on two separate days. The infant monkeys inhaled an aerosolized dose of oxytocin in one session, and a dose of saline in the other. In each session, the dose was delivered through an inhalation mask held gently over the animal’s face. Results showed that overall, the monkeys were more communicative after receiving oxytocin, more frequently making facial gestures, than they were after receiving the saline. The monkeys were more likely to engage in lip smacking than tongue protrusion, but were more likely still to engage in either of these gestures after oxytocin than after the saline. There also were differences in the frequency of gesturing among the individual monkeys, with the strong imitators becoming even stronger imitators after receiving oxytocin. In addition, after oxytocin exposure, the strong imitators were more likely to look at caregivers and stand close to them than they were after the saline. Looking into a caregiver’s face and remaining in close proximity to a caregiver are indicators of social interaction and social interest, according to the authors.
In another test, the authors found that after exposure to oxytocin, monkeys had lower levels of cortisol in their saliva. Cortisol is produced by the adrenal glands in response to stress. Lower cortisol levels after oxytocin exposure indicate that oxytocin may also function to diminish anxiety.
Estriol Plus Copaxone Show Improvement in MS Symptoms
Glatiramer acetate (also known as Copolymer 1, Cop-1, or Copaxone – as marketed by Teva Pharmaceuticals) is an immunomodulator drug currently used to treat multiple sclerosis (MS). It is a random polymer of four amino acids found in myelin basic protein, namely glutamic acid, lysine, alanine, and tyrosine, and may work as a decoy for the immune system. Glatiramer acetate is approved by the Food and Drug Administration (FDA) for reducing the frequency of relapses, but not for reducing the progression of disability. Observational studies, but not randomized controlled trials, suggest that it may reduce progression of disability.
MS is an autoimmune disorder in which immune cells break down myelin, a protective covering that wraps around nerve cells. Loss of myelin results in pain, movement and balance problems as well as changes in cognitive ability. Relapsing remitting multiple sclerosis (RRMS) is the most common form of the disorder. Patients with RRMS experience relapses, or flare-ups, of neurological symptoms, followed by recovery periods during which the symptoms improve.
According to preliminary results from a clinical study of 158 patients with relapsing remitting multiple sclerosis (RRMS), presented on April 29, 2014 at the American Academy of Neurology Annual Meeting in Philadelphia, combining the estrogen hormone estriol with Copaxone, may improve symptoms in patients with the RRMS.
Numerous laboratory studies have suggested that estrogen may have neuroprotective effects and may help decrease inflammation, which occurs in MS. In addition, it has been reported that MS patients experience improvement in symptoms during the phase of pregnancy when levels of estrogen increase. However, studies looking at the effects of estrogen therapy on women’s health have shown mixed results. Estriol, the form of estrogen examined in this study, is only produced in the body during pregnancy.
In this two-year study, patients received Copaxone along with 8 milligrams per day of estriol or placebo pills. The primary goal of the trial was to determine if estriol helped decrease the number of relapses experienced by RRMS patients who were also taking Copaxone. Results showed that at 12 months, estrogen combination therapy was associated with a greater reduction in relapse rates compared to Copaxone and placebo. However, at 24 months, the difference between the treatment groups was not as great as it was at 12 months.
According to the NIH, while these results are encouraging, the results of this Phase II study should be considered preliminary as a larger study would be needed to know whether benefits outweigh the risks for persons affected by MS. The authors added that at present, they cannot recommend estrogen as part of standard therapy for MS and encourage patients to talk with their doctors before making any changes to their treatment plans.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
FDA Has Approved Zykadia for Late-Stage Lung Cancer as a Breakthrough Therapy
The FDA has granted accelerated approval to Zykadia (ceritinib) for patients with a certain type of late-stage (metastatic) non-small cell lung cancer (NSCLC). This breakthrough therapy drug was approved four months ahead of the review completion goal date.
Lung cancer is the leading cause of cancer-related deaths among men and women. According to the National Cancer Institute, an estimated 224,210 Americans will be diagnosed with lung cancer, and 159,260 will die from the disease this year. About 85% of lung cancers are NSCLC, making it the most common type of lung cancer. However, only 2-7% of patients with NSCLC are ALK-positive.
Zykadia is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients with metastatic ALK-positive NSCLC who were previously treated with crizotinib, the only other approved ALK tyrosine kinase inhibitor.
According to Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the CDER, the approval illustrates how a greater understanding of the underlying molecular pathways of a disease can lead to the development of specific therapies aimed at these pathways, and it also demonstrates FDA’s commitment to working cooperatively with companies to expedite a drug’s development, review and approval, reflecting the promise of the breakthrough therapy designation program.
Zykadia is the fourth drug with breakthrough therapy designation to receive FDA approval. It is being approved four months ahead of the product’s prescription drug user fee goal date of Aug. 24, 2014, the date the agency was scheduled to complete review of the drug application. The FDA granted Zykadia breakthrough therapy designation, priority review and orphan product designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; the drug had the potential, at the time of the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively.
The FDA approeved Zykadia under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.
Zykadia’s safety and effectiveness were established in a clinical trial of 163 participants with metastatic ALK-positive NSCLC. All participants were treated with Zykadia. Results showed that about half of the participants had their tumors shrink, and this effect lasted an average of about seven months. Common side effects of Zykadia include gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Laboratory abnormalities such as increased liver enzymes, pancreatic enzymes and increased glucose levels were also observed.
Zykadia is marketed by Novartis, based in East Hanover, N.J.
Amaretto Dessert Cake and/or Almond Coffee Cake
©Joyce Hays, Target Health Inc.
Mea culpa, mea culpa – this is not a health food or even a healthy recipe. Every once in a while my craving takes over and I give in to ingredients like the ones in this yummy cake.
In the beginning, the rationale was to create a flourless cake. Some of the flourless chocolate cakes out there are really good. I wanted to come up with a flourless almond cake that would also soak in some liqueur well, if desired.
Although, this recipe is two in one, I really prefer the dessert cake soaked in Amaretto liqueur better than the coffee cake. I must say, though, my husband loves both versions.
I find the coffee cake a little too dry, but he likes it. I think the coffee cake version would be a little better with some butter added to the recipe, but I chose not to do that, in order to keep the calorie count down. You could choose to add butter to the recipe at number 4 in the directions. (Add 1 stick or 1/2 stick of very soft butter to the bowl after the eggs, whisk and continue).
©Joyce Hays, Target Health Inc.
2 cans almond paste
3/4 cup sliced almonds
1 cup slivered almonds, toast them before using
Spray canola oil
6 large eggs
1/2 cup splenda
1 teaspoon salt
2 cups almond flour
2 teaspoons baking powder
Topping: mix together 1 can almond paste and 3/4 cup sliced almonds
©Joyce Hays, Target Health Inc.
1. Toast the almond slivers until golden and set aside
2. Heat oven to 350 degrees.
©Joyce Hays, Target Health Inc.
3. Spray a 9-inch springform pan, once, with canola oil, line bottom with parchment paper and spray paper with oil (1 spray only), spread the oil with pastry brush (I bought mine on Amazon).
4. In a large bowl, whisk the eggs together with the Splenda, salt and 1 can of the almond paste. Add the toasted slivered almonds and mix
©Joyce Hays, Target Health Inc.
5. Add the almond flour and baking powder, slowly, and stir until just combined.
©Joyce Hays, Target Health Inc.
6. Pour into prepared springform pan and bake until edges are golden brown and starting to pull away from sides of pan, about 40 to 45 minutes.
©Joyce Hays, Target Health Inc.
7. Mix together the other can of almond paste with the sliced almonds
8. Remove the cake, after 40-45 minutes and let cool for about 30 minutes.
Cake going back into oven for 5-10 minutes to brown the topping
©Joyce Hays, Target Health Inc.
9. Spread the mixture of almond paste and sliced almonds, over the entire top of the cake.
Put cake back in over for 10 to 15 minutes, until the sliced almonds are toasted and a golden to light brown.
10. Transfer to wire rack set over baking sheet.
11. After 10 minutes, run a knife around edge of pan to loosen cake; remove cake from pan. Peel off parchment paper and return cake to wire rack to cool completely.
Delicious with coffee, tea. breakfast, brunch, dinner, or snack
©Joyce Hays, Target Health Inc.
Drenched with almond liqueur, just before serving, this cake is absolutely an unbelievable hit as the intimate dessert with your significant other, or at a dinner party. This is so-o good, that adding whipped cream is probably, over the top.
©Joyce Hays, Target Health Inc.
©Joyce Hays, Target Health Inc.
Our meal tonight was breaded veal chop with poached egg on top, so this cabernet was
delicious with the veal. We would recommend a sweet dessert wine, or liqueur with the Amaretto cake, as well as coffee or tea. Think about iced decaf Cappuccino as the weather gets warmer.
To all our wonderful appreciative readers from around the world, we wish you a happy successful week.
Bon Appetit !