In the News
First Type 1 Diabetes Patient in Europe is Free from Insulin Therapy after Undergoing Diabetes Research Institute's BioHub Transplant Technique
Natural Molecule Could Improve Parkinson’s
The natural molecule, n-acetylcysteine (NAC), with strong antioxidant effects, shows potential benefit as part of the management for patients with Parkinson's disease, according to a study published today in the journal PLOS ONE. Combining clinical evaluations of a patient’s mental and physical abilities with brain imaging studies that tracked the levels of dopamine, the lack of which is thought to cause Parkinson’s, doctors from the Departments of Integrative Medicine, Neurology, and Radiology, at Thomas Jefferson University showed that patients receiving NAC improved on both measures.
Current treatments for Parkinson's disease are generally limited to temporarily replacing dopamine in the brain as well as some medications designed to slow the progression of the disease process. Recently, researchers have shown that oxidative stress in the brain may play a critical role in the Parkinson's disease process, and that this stress also lowers levels of glutathione, a chemical produced by the brain to counteract oxidative stress. Studies in brain cells showed that NAC helps reduce oxidative damage to neurons by helping restore the levels of the antioxidant glutathione. NAC is an oral supplement that can be obtained at most nutrition stores, and interestingly also comes in an intravenous form which is used to protect the liver in acetaminophen overdose.
"This study reveals a potentially new avenue for managing Parkinson's patients and shows that n-acetylcysteine may have a unique physiological effect that alters the disease process and enables dopamine neurons to recover some function," said senior author on the paper Daniel Monti, MD, MBA, Director of the Myrna Brind Center of Integrative Medicine, and the Brind-Marcus Center of Integrative Medicine at Thomas Jefferson University.
In this study, Parkinson’s patients who continued their current standard of care treatment, were placed into two groups. The first group received a combination of oral and intravenous (IV) NAC for three months. These patients received 50mg/kg NAC intravenously once per week and 600mg NAC orally 2x per day on the non IV days. The second group, the control patients, received only their standard of care for Parkinson’s treatment. Patients were evaluated initially, before starting the NAC, and then after three months of receiving the NAC while the control patients were simply evaluated initially and three months later. The evaluation consisted of standard clinical measures such as the Unified Parkinson’s Disease Rating Scale (UPDRS), a survey administered by doctors to help determine the stage of disease, and a brain scan via DaTscan SPECT imaging, which measures the amount of dopamine transporter in the basal ganglia, the area most affected by the Parkinson’s disease process. Compared to controls, the patients receiving NAC had improvements of 4-9 percent in dopamine transporter binding and also had improvements in their UPDRS score of about 13 percent.
“We have not previously seen an intervention for Parkinson’s disease have this kind of effect on the brain,” said first author and neuro-imaging expert Andrew Newberg, MD, Professor at Sidney Kimmel Medical College at Jefferson and Director of Research at the Myrna Brind Center of Integrative Medicine. The investigators hope that this research will open up new avenues of treatment for Parkinson's disease patients.
This study was funded by a gift from the Marcus Foundation. The authors report no conflicts of interest.
Article reference: DA Monti, et al., “N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson’s Disease: Preliminary Clinical and Cell Line Data,” PLOS ONE, DOI: 10.1371/journal.pone.0157602 , 2016.
Key Enzyme Keeps Antibodies from Targeting DNA and Driving Inflammation in Lupus
Failure of an enzyme to break down DNA spilling into the bloodstream as cells die may be a major driver of inflammation in lupus. This is the finding of a study in both mice and human patients led by researchers at NYU Langone Medical Center and published online June 9 in the journal Cell.
The study revolves around the constant, healthy turnover of mammalian cells, which die, break up, and have their parts, including DNA, recycled. Researchers found that an enzyme, DNASE1L3, normally digests the DNA within small particles issuing from disintegrating cells, thereby preventing lupus.
Without DNASE1L3 to prevent its buildup, accumulating DNA triggers immune cells to produce proteins called antibodies that glom onto and remove the DNA. Such antibodies, when attached to DNA in complexes, get lodged in the walls of arteries and in tissues to cause inflammation that damages blood vessels, skin, joints, and the kidneys as part of the most severe type of lupus, systemic lupus erythematosus (SLE).
"Our study reveals a new mechanism that could be harnessed for biological therapies for lupus and other autoimmune diseases, where the immune system mistakenly targets the body's own cells," says senior study author Boris Reizis, PhD, professor of Pathology and Medicine at NYU Langone.
Specifically, the study authors were able re-create lupus disease processes, including the formation of antibodies to DNA and kidney inflammation, by engineering mice that lacked the gene for DNASE1L3.
"We also confirmed that human patients with a missing or malfunctioning DNASE1L3 gene had an abundance of circulating DNA and developed antibodies to it, and that such antibodies were also present in most forms of lupus," says Reizis. "This opens up a potential avenue for a new treatment, including the possibility of administering DNASE1L3 as a drug."
The need to find new treatments is urgent, adds Reizis, because there have been few advances in the treatment of lupus in 50 years, and the drugs used traditionally are poorly tolerated.
Other NYU authors included Vanja Sisirak, Benjamin Sally, Wilnelly Martinez-Ortiz, Joseph David, Ali Rashidfarrokhi, and Timothy Cardozo. The study of human patients was done in collaboration with co-authors Robert Clancy and Jill Buyon, director of the Division of Rheumatology and of NYU Lupus Center. The research was supported by NIH grants AR064460 and AI072571, the Lupus Research Institute, and The Judith and Stewart Colton Center for Autoimmunity.
First Type 1 Diabetes Patient in Europe is Free from Insulin Therapy after Undergoing Diabetes Research Institute's BioHub Transplant Technique
A 41-year-old man who was diagnosed with type 1 diabetes at age 11 has become the first patient in Europe to discontinue insulin therapy after receiving a transplant of pancreatic islet cells using an innovative technique developed by the Diabetes Research Institute (DRI) at the University of Miami. Following the DRI's BioHub protocol, Drs. Federico Bertuzzi, head of the Islet Transplant Program, Mario Marazzi, head of the Tissue Therapy Unit, Luciano De Carlis, director of General Surgery and Transplantation, and collaborators at Ospedale Niguarda Ca' Granda in Milan, Italy, transplanted the insulin-producing cells within a biological scaffold engineered onto the surface of the omentum, a highly vascularized tissue covering abdominal organs. This successful post-transplant outcome confirms the initial results achieved by the Diabetes Research Institute in August of 2015.
Ospedale Niguarda Ca' Granda is a member of the worldwide Diabetes Research Institute Federation, a global alliance of researchers and medical centers that collaborate and share promising findings in order to accelerate research toward a cure for diabetes. After completion of the first BioHub transplant, DRI researchers shared their transplant protocol with DRI Federation members with the goal replicating these results quickly to help the millions living with type 1 diabetes around the world.
"I warmly congratulate the team of Niguarda, the first team of the DRI Federation in Europe and in the world to have confirmed the initial results achieved last year in Miami. This tissue engineering technique will be essential for allowing clinical testing of new technologies for preventing the use of anti-rejection drugs which currently limit the applicability of islet transplantation to the most severe cases of type 1 diabetes," said Camillo Ricordi, MD, director of the DRI and the Stacy Joy Goodman Professor of Surgery, Distinguished Professor of Medicine, Professor of Biomedical Engineering, Microbiology and Immunology at the University of Miami Miller School. Dr. Ricordi also serves as director of the DRI's Cell Transplant Center.
Dr. Ricordi and collaborators from the DRI at UM have been providing assistance to selected teams worldwide by sharing protocols, equipment and through the DRI's telescience platform, which enables researchers in different parts of the world to "virtually" work together side by side.
"Our team is building on decades of progress in clinical islet transplantation toward the development of the DRI BioHub, a bioengineered mini organ that mimics the native pancreas to restore natural insulin production in people with type 1 diabetes," said Dr. Ricordi.
In this latest procedure, as was done in Miami, the donor islets were implanted within a biodegradable scaffold, one of the platforms for a DRI BioHub, made by combining the patient's own blood plasma with thrombin, a commonly used clinical-grade enzyme. Together, these substances create a gel-like material that sticks to the omentum and holds the islets in place. The omentum is then folded over around the biodegradable (biological) scaffold mixture. Over time, the body will absorb the gel, leaving the islets intact, while new blood vessels are formed to provide critical oxygen and other nutrients that support the cells' survival.
In type 1 diabetes, the insulin-producing islets cells of the pancreas have been mistakenly destroyed by the immune system, requiring patients to manage their blood sugar levels through a daily regimen of insulin therapy. Islet transplantation has allowed some patients to live without the need for insulin injections after receiving a transplant of donor cells. Some patients who have received islet transplants at the DRI have been insulin independent for more than a decade, as DRI researchers have published.
Currently, islet cells are infused into the liver, but many of the cells do not survive in that environment. Most importantly, the reason for developing this alternative site is that the BioHub technology will eventually allow for the introduction of additional technologies and components to eliminate the need for anti-rejection drugs. This FDA-approved Phase I/II BioHub clinical trial is testing the omentum as an alternative transplant site.
About the Diabetes Research Institute
The Diabetes Research Institute at the University of Miami Miller School of Medicine leads the world in cure-focused research. As the largest and most comprehensive research center dedicated to curing diabetes, the DRI is aggressively working to develop a biological cure by restoring natural insulin production and normalizing blood sugar levels without imposing other risks. Researchers have already shown that transplanted islet cells allow patients to live without the need for insulin therapy. The DRI is now building upon these promising outcomes by developing the DRI BioHub and is testing various BioHub platforms in preclinical and clinical studies. For more information, please visit DiabetesResearch.org. You can tweet DRI at @Diabetes_DRI.
AIHM Interprofessional Fellowship Breaks New Ground with Scholarships
The Academy of Integrative Health & Medicine (AIHM), the leading provider of education and training in the field of integrative medicine and holistic health, announced an unparalleled number of scholarship opportunities for their Interprofessional Fellowship program. Of the 60 inaugural Interprofessional Fellows, 19 received scholarships when the program launched in February. AIHM confirmed that the same level of support would be provided to the next class, which is filling now and commences late this summer.
The AIHM Interprofessional Fellowship is a groundbreaking, two-year, 1000-hour hybrid training model with online, in-person, and clinical components, designed to give rise to the next generation of interprofessional collaborations and to activate fundamental, systemic change in the healthcare system. The program is open to all licensed health providers holding at least a master’s degree in their field. According to Founding Fellowship Director, Tieraona Low Dog, MD, “Our best hope for changing the trajectory of the health of our people and our planet is to bring together health professionals in a spirit of mutual respect and collaboration. We want to attract bold thinkers with shared values across multiple professions regardless of financial capacity.” Scholarships are considered an important lifeline for many practitioners interested in advanced training because earning capacity varies widely among professions and even within professions, especially for those working in underserved areas.
When Fellows successfully complete their training, they emerge as experts in interprofessional team coordination, integrative medicine, and health promotion. MD and DO graduates will have met the American Board of Integrative Medicine (ABOIM) Fellowship Requirement and are eligible to sit for board certification.
Scholarships for the 2016-2017 year have been made possible through a commitment by the AIHM Board and philanthropic leaders, including the Westreich Foundation, Integrative Therapeutics, Council for Responsible Nutrition, Food State, and the Miraglo Foundation.
“Our Interprofessional Fellowship is as ambitious as the outstanding Fellows whose educational and career aspirations we support,” said AIHM President, Mimi Guarneri, MD. “We invite people to make an investment that will pay dividends for Fellows, for our entire community, and the field of integrative health and medicine as a whole. Together, we are building a new healthcare landscape.”
The first Integrative Therapeutics Scholarship was awarded to Gretchen E. Seitz, DAOM, LAc; a family medicine clinician in San Diego, CA, who serves as the Acupuncture Department Chair at the Pacific College of Oriental Medicine. Dr. Seitz considers the AIHM Interprofessional Fellowship a transformative experience at the personal and professional level. “My profession won’t move forward unless we reach across the table,” she says, “I’m there to learn from my peers, but I am there also to show what my profession has to offer. I feel like a liaison, an ambassador, to help educate. Together, we can serve patients more effectively. I am so in love with it—thank you for the opportunity.”
Applications for the next AIHM Interprofessional Fellowship class, which starts August 21, are being accepted on a rolling basis through August 1. Clinicians are encouraged to apply soon. More information about the program and scholarship opportunities is available at aihm.org/fellowship.