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Lab Chip Device Developed to Test Engineered Plant Traits

Liang Dong with seed chip

Liang Dong with microfluidic seed chip (Bob Elbert, Iowa State University)

26 March 2014. Engineers at Iowa State University in Ames created a device about the size of a microscope slide that can quickly test the effects of genetic changes on plant characteristics, rather than growing sample seeds in soil. The team led by electrical and computer engineering professor Liang Dong, with colleagues from Iowa State and Georgia Institute of Technology in Atlanta, appears in the 7 April issue of the journal Lab on a Chip (paid subscription required).

Testing plants with genetically engineered traits, such as drought resistance, and under various environmental conditions, normally requires growing seeds in greenhouses or testing fields, processes taking enormous amounts of time and labor. Dong and colleagues aimed to develop a lab-based system that can provide plant geneticists with the same answers, but much faster and with greater control.

Their solution is, in effect, a greenhouse on a chip, funded by a three-year grant of nearly $700,000 from National Science Foundation. The researchers devised a microfluidic chip, a hand-held clear plastic strip with thin channels housed in the plastic. The channels make it possible for a seed to germinate in in the chip, and for lab staff to monitor plant growth into a seedling from cells to the whole organism, including roots and shoots, without damaging the seed.

Dong and colleagues tested the chip on mutations of Arabidopsis, a small flowering plant related to cabbage and mustard with well-documented genetics and associated plant characteristics, often used as a model in the lab. The chip made it possible for the team to track growth of a mutation of Arabidopsis, as well as changes occuring when the plant encountered a pathogen at different stages of its growth. The two-week time needed for the growth to occur on the chip, report the researchers, was comparable to using conventional lab cultures.

This lab-on-a-chip testing method, say the authors, when combined with high-capacity computing, can usher in high-throughput analysis of plant genetics. Dong’s team is now working on integrating the chip into an overall system for testing engineered genetics against plant traits. The chip itself can be modified to accommodate different growth stages of the plant in question. “If it’s a plant’s first 10 days, we can make parts of the instrument smaller,” says Dong in a university statement. “If it’s four weeks, we make them bigger.”

Dong envisions hundreds of greenhouse lab chips growing thousands of plants simultaneously, with each chip representing a different environmental condition: e.g., humidity, temperature, carbon dioxide, or pathogens. Robotic arms would record data and images of the plants’ various characteristics, such as root development and shoot size. The images and data collected would then be stored in databases and made available for analysis by advanced informatics tools.

Agronomist colleagues at Iowa State, reports the university, are not waiting for development of that ultimate system. They are already using parts of Dong’s technology to study germination of pollen at various temperatures and the interaction of fungus pathogens with soybeans at different moisture levels.

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Biotech Group Issues Clinical Trial Data Sharing Guidelines

Bank vault door

(Bill McChesney/Flickr)

25 March 2014. Biotechnology Industry Organization (BIO) today released its principles for sharing data from clinical trials that encourage making more data available from clinical trials, but leave procedures for sharing up to the individual companies. The guidelines cover programs resulting in approved medicines, as well as those discontinued for safety or efficacy reasons, although more details will be made available for approved medicines.

BIO’s membership includes biotechnology companies, academic institutions, and state biotechnology centers in the U.S. and 30 countries, from start-up enterprises to Fortune 500 companies. The group’s members are engaged in research and development of health care, agricultural, industrial, and environmental products based on biotechnology.

The principles call for all sponsored clinical trials to listed in appropriate registries, either ClinicalTrials.gov or European Clinical Trials Database (EudraCT). BIO says its member companies now routinely register intermediate and later-stage trials with ClinicalTrials.gov, as required by the Food and Drug Administration Amendments Act of 2007.

More data will be made available for approved medications, such as Clinical Study Reports, clinical data sets to the individual patient level, and clinical study designs and protocols, to qualified researchers. Each company, however, will set its own criteria and processes, including the definition of qualified researchers.

BIO members will also make summaries of clinical trials available in databases, whether the products are approved or discontinued, or results are positive or negative. The guidelines, however, do not make a firm commitment to share summaries of clinical trials with participants in clinical trials, only to “work with regulators to adopt a framework for developing and sharing factual summaries of clinical trial results” with people taking part in trials.

The guidelines call for companies to make publish in scientific literature all results of late-stage clinical trials, and other clinical studies “of significant medical importance,” whether the findings are positive or negative. Publications can include scientific journals, professional meetings, or a company’s own Web site.

“BIO recognizes that responsible clinical trial data sharing advances public health and scientific discourse, honors research participants’ expectations of privacy through informed consent, and promotes biomedical innovation,” says BIO president Jim Greenwood in an organization statement. “These Principles reaffirm our support for these efforts, and represent a commitment to make additional information available to the public, qualified researchers, and patients participating in clinical trials.”

In July 2013, the European Federation of Pharmaceutical Industries and Associations and Pharmaceutical Research and Manufacturers of America issued joint principles for expanding access to clinical trial data for scientists and trial participants.

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Light-Activated Coating Kills Bacteria, Even in Dark

Samples of silicone with various dyes infused

Samples of silicone with various dyes infused (Sacha Noimark, Elaine Allan and Ivan P. Parkin, University College London)

25 March 2014. Chemistry researchers at University College London in the U.K. developed a material that when coated on surfaces in the lab can kill bacteria when exposed to light, as well as in total darkness. The team led by UCL chemistry professor Ivan Parkin published its findings online earlier this month in the journal Chemical Science (paid subscription required).

The research was funded by Ondine Biomedical in Vancouver, British Columbia, Canada that first licensed UCL’s research in 2008. In 2011, Ondine and UCL received a grant of £1 million ($US 1.65 million) from the U.K.’s Medical Research Council to develop a light-activated anti-microbial application to prevent catheter-associated infections. UCL holds a patent on the technology.

Parkin and colleagues from UCL’s chemistry department and dental school designed the technology to meet the need for better tools to control infections in health care facilities, those acquired by patients in hospitals and clinics. According to the U.S. Centers for Disease Control and Prevention, about 1 in 20 hospitalized patients gets an infection when receiving medical care. Even with stringent cleaning and hand-washing policies, infections in hospitals remain difficult to control.

The UCL researchers address the problem differently, by creating surfaces hostile to microbes, to keep pathogens from accumulating on surfaces of equipment, keyboards, and door handles. The technology combines gold nanoparticles mixed with known anti-microbial dyes that react to light. As Parkin explains in a university statement, “The light excites electrons in them, promoting the dye molecules to an excited triplet state and ultimately produces highly reactive oxygen radicals that damage bacteria cell walls.”

The team still had to solve the problem of binding this anti-microbial compound to surfaces and equipment used in hospitals and clinics. They found a simple method of infusing silicone polymer rubber used on a wide variety of medical equipment with a solvent that swelled the silicone to penetrate the anti-microbial compound into the material. They then dipped the infused material into the compound to form a a thin layer on the surface, that in tests remained stable even when wiped with alcohol or exposed to light.

The UCL researchers tested combinations of crystal violet and methylene blue dyes mixed with gold particles as small as 2 nanometers — 1 nanometer equals 1 billionth of a meter. The tests were conducted with E. coli and Staphylococcus epidermidis bacteria known to form on catheters and other hospital devices, and under realistic lighting conditions, such as fluorescent lights.

Even with quantities of bacteria far greater than found in hospitals, say the researchers, the treated surfaces were able to kill all of the bacteria in 3 to 6 hours. As lead author and postdoctoral researcher Sacha Noimark notes in a university statement, they were surprised to discover a sample left in the dark also “showed significant reductions in bacterial load, albeit over longer timescales of about 3 to 18 hours.”

Ondine Biomedical’s technology platform, called photodisinfection, uses lasers to activate anti-microbial activity on surfaces. This new discovery, if developed further by Ondine, would expand its capabilities into activation under normal lighting conditions.

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Early Trial Shows Wireless Pacemaker Safe, Effective

Nanostim pacemaker and Euro coin

Nanostim pacemaker compared in size to Euro coin (St. Jude Medical Inc.)

24 March 2014. Researchers at Mount Sinai Hospital in New York found in an early-stage clinical trial, a smaller and lead-less heart pacemaker could be safely implanted and operate for at least three months without complications. The team led by Mount Sinai cardiologist Vivek Reddy — with colleagues in Netherlands, Germany, and Czech Republic, and the company Nanostim Inc. that developed the device — published its findings online today in the journal Circulation, published by American Heart Association (paid subscription required).

Nanostim, in Sunnyvale, California, sponsored the trial. The company was acquired by medical device manufacturer St. Jude Medical in October 2013 for $123.5 million in cash, plus up to $65 million in future milestone payments.

Pacemakers are implanted in patients with an irregular or slower than normal heart rate, and generate normal-paced electrical impulses through thin wires into the heart called leads, which also sense the patient’s heart rhythm to send a compensating electrical signal. These conventional pacemakers are surgically implanted under the patient’s collarbone, with the leads running to the heart. The leads, however, need time to set requiring the patient to keep the area around the pulse generator inactive for a few weeks, to prevent disconnecting. Surgical implants also run a risk of infection around the implant site.

The Nanostim device is about one-tenth the size of a conventional pacemaker and self-contained with a battery, circuitry, and sensors sitting inside the heart, removing the need for wire leads. It is designed for patients needing to stimulate one chamber of the heart, a condition affecting 20 to 30 percent of patients requiring pacemakers. The device is inserted with a minimally-invasive procedure using a catheter that sends the device through the femoral vein in the thigh into the heart. It can also be repositioned or retrieved after initial implant, such as for battery replacement.

Reddy and colleagues tested the safety of the implantation procedure and initial clinical performance of the Nanostim device in an early-stage clinical trial with 33 patients in the Netherlands and Czech Republic having a slow or irregular heartbeat. Two-thirds of the patients were male, with an average age of 77.

Nearly all — 32 of 33 — patients had their devices implanted without complication, although 5 patients required implanting more than one device during the procedure. One patient developed complications during the implantation and later died from a stroke. After 3 months, 31 of the original 33 patients reported the lead-less devices were operating properly, with their heart pacing either improved or stable.

A later-stage clinical trial of the Nanostim device, sponsored by St. Jude Medical, is currently recruiting 667 patients. Reddy is the study director, with Mount Sinai Hospital listed as one of the sites.

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FDA Approves Celgene Psoriatic Arthritis Treatment

X-ray of arthritic hands

(NIH)

24 March 2014. The U.S. Food and Drug Administration on 21 March approved the drug apremilast to treat adults with active cases of psoriatic arthritis. The drug is marketed as Otezla by the pharmaceutical company Celgene in Summit, New Jersey, that also reported results of clinical trials of Otezla to treat the related  skin condition plaque psoriasis, the most common form of psoriasis.

Psoriatic arthritis is a form of arthritis causing joint pain and swelling, but for most people with the condition, it starts as psoriasis, with red, flaky, and scaling skin. In both cases, the conditions are caused by faulty signals sent by the body’s immune system. In the case of psoriasis, the faulty signals tell skin cells to grow too quickly. For psoriatic arthritis, the signals create inflammation in the joints. Causes for both conditions are believed to be genetic and environmental.

Otezla restricts the actions of an enzyme called phosphodiesterase 4 that impairs the ability of cells to send signals moderating immune-system activity. Without that ability to control immune system activity when it’s not needed, the body misinterprets these signals resulting in the joint inflammation of psoriatic arthritis, and red, scaly skin in psoriasis.

Celgene tested Otezla as a treatment for psoriatic arthritis in three late-stage clinical trials with nearly 1,500 patients taking the drug in doses or 20 or 30 milligrams, or a placebo, twice a day for 16 weeks. The three trials enrolled patients who did not respond earlier to treatments with disease-modifying anti-rheumatic drugs or biologics. After 16 weeks, patients taking Otezla experienced less pain and swelling in and around their joints. Other indicators of psoriatic arthritis as defined by American College of Rheumatology also improved, as well as overall physical functioning.

In addition, the company reported this past weekend at a meeting of American Academy of Dermatology the results of two late-stage clinical trials testing Otezla as a treatment for moderate to severe plaque psoriasis over 52 weeks. The trials tested the drug against a placebo with 1,257 patients. One group, selected at random took 30 milligrams of Otezla twice a day for 16 weeks, while a second randomized group took a placebo. After 16 weeks, the original placebo group started taking Otezla, while the original group taking Otezla was randomly divided between Otezla and a placebo, which continued to week 32.  At that point, patients who responded favorbly to the drug were re-randomized to taking more Otezla or a placebo to week 52.

The company says results showed improvements in a standard psoriasis area and severity index of 81 to 88 percent among the groups of patients taking Otezla over the 52 weeks, compared to the placebo. Patients taking the drug from week 16 to week 32 showed similar results. Celgene also reports patients taking Otezla for 52 weeks also showed more positive results, compared to a placebo, with hard-to-treat areas such as nails and scalp, scoring 60 to 73 percent increases on standard indexes for those regions.

In both sets of trials, the company reports no difference in serious adverse events between treatment and placebo patients. The most common adverse side effects were diarrhea, nausea, headache, upper respiratory tract infection, vomiting, and upper abdominal pain.

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Hat tip: FirstWord Pharma

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New Jersey Tech, IT Company to Develop Autism Device

Face Read app screen shot

Screen shot from Face Read 1, an app to help children with autism recognize facial expressions and emotions. (WebTeam Corp.)

21 March 2014. Engineers at New Jersey Institute of Technology in Newark and WebTeam Corp. in Somerset, New Jersey are designing a device to help children with autism spectrum disorders develop basic educational skills. Financial details of the collaboration were not disclosed, but NJIT and WebTeam will share the intellectual property arising from the project.

WebTeam develops educational software for special needs students, including children with autism spectrum disorders, from infants through teenagers. Autism spectrum disorders include autism, as well as several other related conditions such as Asperger syndrome, Rett’s disorder, and childhood disintegrative disorder. Symptoms of these disorders vary and range from mild to severe. In general, children with autism spectrum disorders have communication difficulties, show social impairment, and exhibit repetitive and stereotyped behaviors.

Educating children with autism spectrum disorders requires special interventions building language and communication, social skills, daily living skills, cognitive skills, and techniques to reduce tantrums and aggression. WebTeam says the financial cost of dealing with autism and related conditions is estimated at $3.2 million over a person’s lifetime, which can be sharply reduced by early diagnosis and intervention.

The company, founded in 2005, develops autism screening software provided as mobile apps to help teachers evaluate students’ learning goals, and register observations to keep track of assessment results. The company also designs skill-building apps for children and adults with autism, and says since January 2012, its autism apps have registered 1.2 million downloads.

The project with NJIT will build a tactile-friendly device to provide learning experiences to children with autism spectrum disorders. The device is expected to to prompt children through their lessons and have built-in sensors to monitor responsiveness, assess cognition, and adapt further lessons based on the child’s interactions.

The outer form of the device, says NJIT, will be adjusted to met the individual needs of the children. For example, the device could be embedded in a familiar toy or interactive robot. The equipment in any form will be designed to work with WebTeam’s iLearnNEarn app software. The educational sessions are based on a curriculum built by Eden Autism Services, a not-for-profit organization in Princeton, New Jersey.

Engineering professor Atam Dhawan will lead the NJIT team, which is expected to include students working on a learning device for children with autism disorder since 2011. “WebTeam has developed the program,” says Dhawan in a university statement, “and we will deliver it, optimizing its interface, as well as its assessment, feedback, and response capabilities, while also capturing the data.”

Under the agreement, NJIT is filing a joint patent with WebTeam for new technology developed in the collaboration, as a supplement to WebTeam’s current patents on its software.

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Process Devised to Generate Stem Cells from Drop of Blood

Drop of blood

(Mattia Belletti/Flickr)

20 March 2014. Researchers at Singapore’s Institute of Molecular and Cell Biology developed a process for deriving adult stem cells from small samples of blood, making it easier for donors to collect and bank their own blood samples. The team led by the institute’s Jonathan Yuin-Han Loh and funded by Singapore’s Agency for Science, Technology and Research (A*STAR) published its findings online yesterday in the journal Stem Cell Translational Medicine.

Human induced pluripotent stem cells are adult stem cells genetically reprogrammed to behave like embryonic stem cells, and thus can be transformed into new tissue or organs. Loh, with colleagues from the U.S., U.K., and other Singapore institutions, were seeking a way to make it easier for individuals to collect their own blood for stem cell reprogramming than current invasive methods using bone marrow or skin samples.

The researchers first took blood samples from two donors with 2 milliliters (0.07 fluid ounces) provided for baseline measurements. With those samples, the team reprogrammed the blood cells into immune system T cells and other cells, using today’s standard technologies. As the researchers reduced the amount of blood in the samples, the use of standard purification techniques failed to isolate sufficient numbers of blood cells needed for reprogramming.

At quantitites of 10 microliters of blood, less than the amount of blood from a finger prick, the team changed the purification techniques, leaving out a method for isolating lymphocytes, but keeping a technique needing less water to break down the cells. Using this technique with 10 microliter blood samples from four of the five young adult donors, age 19 to 36, the researchers were able to culture enough cells for reprogramming into induced pluripotent stem cells.

The reprogrammed stem cells were able to be transformed in lab cultures into precursor cardiomyocytes or human heart muscle cells that were even rhythmically beating. The cardiomyocytes showed as well evidence of potential growth into tissue for specific areas of the heart, such as ventricular and atrial tissue. The researchers also injected the reprogrammed stem cells into immune-deficient mouse hosts, where the stem cell lines began transforming into embryonic skin, cartilage, and nerve cells.

The early results, while encouraging, were not uniform across all of the donated samples. Blood samples from one of the five donors did not reprogram into enough stem cells, suggesting there may be variations in the ability of small blood samples to be reprogrammed into stem cells.

Loh and colleagues believe their techniques can help expand the practice of collecting blood samples for reprogramming into stem cells for research, drug discovery, and cell therapy. The samples remained stable for 48 hours, and for up to 12 days in lab cultures. Making it easy to collect a blood sample from a finger prick at home, say the researchers, can increase the number and types of stem cells across more regions, ethnic groups, and genetic types.

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Smartphone App for Point-of-Care Diagnostics in Development

Colorimetrix in use

(Colorimetrix.com)

20 March 2014. Engineers at University of Cambridge in the U.K. designed a smartphone app that accurately performs tests with urine or saliva samples at the point of care. The app, called Colorimetrix, is the work of Leo Martinez-Hurtado, now a postdoctoral researcher at Technical University of Munich and Cambridge Ph.D. candidate Ali Yetisen, who published advance results of tests with the app online in the journal Sensors and Actuators B: Chemical (paid subscription required).

Colorimetrix performs colorimetric tests measuring the amount of light passing through a sample of body fluid, such as saliva or urine. A sensor detects and measures the amount of light absorbed by the sample, then relates the change in color to specific chemical reactions, as well as concentrations of target chemicals in the fluid sample.

Medical diagnostics with colorimetry are difficult to  conduct outside the lab, and up to now required expensive equipment such as spectrophotometers to get accurate and reliable results. Colorimetrix, however, makes it possible to perform these tests with a smartphone, returning results in a few seconds, or if needed, transmitted to a physician for further review.

The app uses the smartphone’s camera to snap a photo of the sample, which the app’s built-in sensor and algorithms analyze and compare to benchmarks stored in the software. The algorithms process the light waves from the specimen and calculates the concentrations of analytes. The software then returns a numerical score on the smartphone’s screen.

Yetisen, Martinez, and colleagues evaluated Colorimetrix against commercially-available test strips used with urine samples, described in the journal article. The results indicate the app accurately reports glucose, protein, and pH concentrations without the need for additional equipment. The team plans to test the app for kidney functions and infections at Addenbrooke’s Hospital, affiliated with the university.

The developers designed Colorimetrix for use in limited-resource regions to diagnose HIV, tuberculosis, or malaria at the point of care, but it can also be used to monitor chronic diseases such as diabetes, or to track transmission of medical data to health professionals in real time. Other potential applications are veterinary health and environmental testing.

The Colorimetrix team is seeking partners for further commercial development. The app is now in an early version (0.2) and available for the Android operating system from its Web site. Feasibility of an Apple iPhone (iOS) version is under review.

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Genetics Group, Analytics Firm Collaborate on Diagnostics

DNA Strands (NIST.gov)

(NIST.gov)

19 March 2014. A genetics research center at University of Utah in Salt Lake City and Omicia Inc., a genomic analytics company in Oakland, California are developing systems to make genomic analysis a routine medical diagnostic procedure. The $6 million in funding for the USTAR Center for Genetic Discovery comes from the university and Utah Science Technology and Research (USTAR) an initiative of the state government.

The USTAR Center is directed by Utah genetics professor Mark Yandell and Gabor Marth, a computer scientist who recently joined the Utah medical faculty from Boston College. Their goal is to make it possible to quickly sequence an individual’s entire genome to uncover underlying genetic causes for disease. The results would make it possible, say Yandell and Marth, to prescribe more customized and cost-effective treatments for the patient’s condition, as well as prevent further disorders.

While the time and cost of sequencing the human genome are much lower than 10 years ago, the mountain of data generated from sequencing still need a good deal of analysis and interpretation to make them useful for clinicians. “Current systems,” says Marth in a university statement, “are not prepared for the increasing amounts of data we will be seeing within the next few years.”

Yandell’s lab wrote an algorithm called the Variant Annotation, Analysis and Search Tool or VAAST, now in its second version, that identifies with probability processes genetic variations and damaged genes in an individual’s genome as potential causes of disease. The university says VAAST is in use at more than 250 institutions.

Omicia is working with Yandell and Marth to further develop the company’s cloud-based genomic analysis toolkit, called Opal. In 2012, Omicia received a Small Business Innovation Research grant from National Human Genome Research Institute, part of NIH, to integrate VAAST into Opal. The company launched Opal that same year.

Opal, says the company, analyzes genomes to find disease-causing variants and damaged genes, making the highlighted causes easier to identify, and presented in a format useful for physicians, with cross-references to scientific literature. The system, says Omicia, can process exomes — the regions of the genome translated into proteins — in under one hour, while whole genomes can be processed in under three hours.

The USTAR Center is collaborating as well with the Utah Genome Project, an undertaking that combines genealogical and health records dating back to pioneer days to find genetic causes of cancer, cardiovascular diseases, and immune disorders. The center expects to eventually commercialize its full line of genetic software.

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Janssen, Univ. of Alberta Partner on Diabetes Research

Diabetes test (HHS.gov)

(HHS.gov)

19 March 2014. Janssen Pharmaceutical Companies, a division of Johnson & Johnson, is joining with University of Alberta in Edmonton to fund research on diabetes with commercial potential. The $600,000 fund, with contributions from Janssen and matched by the government of Alberta and Alberta Diabetes Foundation, will support studies on type 1 and type 2 diabetes.

The Alberta Diabetes Institute – Johnson & Johnson Diabetes Research Fund will support research by single investigators or teams based in Alberta, with grants of up to $50,000 for one year, covering both direct and indirect costs. Letters of intent to Alberta Diabetes Institute are due on 30 April 2014. Researchers with the most promising ideas will be invited to prepare full proposals.

The letter of intent instructions call for preclinical studies with the “potential to alter the course of existing treatment or diagnosis for type 1 or 2 diabetes patients.” The studies should seek out novel and highly innovative ideas with a high potential for commercialization. Findings are expected to lead to further development of drugs, devices, cell therapies, and processes, covering all aspects of diabetes diagnosis, treatment, and management.

A review committee from Alberta Diabetes Institute, in University of Alberta’s medical school, and the Johnson & Johnson Innovation Center in Menlo Park, California will review letters of intent and select the leading candidates by 23 May 2014. Full proposals from the finalists will be due by 25 July, with the selected researchers notified by 26 September.

University of Alberta is no stranger to diabetes discoveries. A method of pancreatic islet transplantation, known as the Edmonton protocol, to improve blood glucose control and reduce the need for insulin injections, was developed at the university in 2000. The protocol recommends a combination of medications to suppress the immune system and reduce the risk of rejection from the transplants.

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