Tag Archives: type 1 diabetes

Bionic pancreas tested at home

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This news about a bionic pancreas must be exciting for diabetics as it would eliminate the need for constant blood sugar testing throughout the day. From a Dec. 19, 2016 Massachusetts General Hospital news release (also on EurekAlert), Note: Links have been removed,

The bionic pancreas system developed by Boston University (BU) investigators proved better than either conventional or sensor-augmented insulin pump therapy at managing blood sugar levels in patients with type 1 diabetes living at home, with no restrictions, over 11 days. The report of a clinical trial led by a Massachusetts General Hospital (MGH) physician is receiving advance online publication in The Lancet.

“For study participants living at home without limitations on their activity and diet, the bionic pancreas successfully reduced average blood glucose, while at the same time decreasing the risk of hypoglycemia,” says Steven Russell, MD, PhD, of the MGH Diabetes Unit. “This system requires no information other than the patient’s body weight to start, so it will require much less time and effort by health care providers to initiate treatment. And since no carbohydrate counting is required, it significantly reduces the burden on patients associated with diabetes management.”

Developed by Edward Damiano, PhD, and Firas El-Khatib, PhD, of the BU Department of Biomedical Engineering, the bionic pancreas controls patients’ blood sugar with both insulin and glucagon, a hormone that increases glucose levels. After a 2010 clinical trial confirmed that the original version of the device could maintain near-normal blood sugar levels for more than 24 hours in adult patients, two follow-up trials – reported in a 2014 New England Journal of Medicine paper – showed that an updated version of the system successfully controlled blood sugar levels in adults and adolescents for five days.  Another follow-up trial published in The Lancet Diabetes and Endocrinology in 2016  showed it could do the same for children as young as 6 years of age.

While minimal restrictions were placed on participants in the 2014 trials, participants in both spent nights in controlled settings and were accompanied at all times by either a nurse for the adult trial or remained in a diabetes camp for the adolescent and pre-adolescent trials. Participants in the current trial had no such restrictions placed upon them, as they were able to pursue normal activities at home or at work with no imposed limitations on diet or exercise. Patients needed to live within a 30-minute drive of one of the trial sites – MGH, the University of Massachusetts Medical School, Stanford University, and the University of North Carolina at Chapel Hill – and needed to designate a contact person who lived with them and could be contacted by study staff, if necessary.

The bionic pancreas system – the same as that used in the 2014 studies – consisted of a smartphone (iPhone 4S) that could wirelessly communicate with two pumps delivering either insulin or glucagon. Every five minutes the smartphone received a reading from an attached continuous glucose monitor, which was used to calculate and administer a dose of either insulin or glucagon. The algorighms controlling the system were updated for the current trial to better respond to blood sugar variations.

While the device allows participants to enter information about each upcoming meal into a smartphone app, allowing the system to deliver an anticipatory insulin dose, such entries were optional in the current trial. If participants’ blood sugar dropped to dangerous levels or if the monitor or one of the pumps was disconnected for more than 15 minutes, the system would alerted study staff, allowing them to check with the participants or their contact persons.

Study participants were adults who had been diagnosed with type 1 diabetes for a year or more and had used an insulin pump to manage their care for at least six months. Each of 39 participants that finished the study completed two 11-day study periods, one using the bionic pancreas and one using their usual insulin pump and any continous glucose monitor they had been using. In addition to the automated monitoring of glucose levels and administered doses of insulin or glucagon, participants completed daily surveys regarding any episodes of symptomatic hypoglycemia, carbohydrates consumed to treat those episodes, and any episodes of nausea.

On days when participants were on the bionic pancreas, their average blood glucose levels were significantly lower – 141 mg/dl versus 162 mg/dl – than when on their standard treatment. Blood sugar levels were at levels indicating hypoglycemia (less than 60 mg/dl) for 0.6 percent of the time when participants were on the bionic pancreas, versus 1.9 percent of the time on standard treatment. Participants reported fewer episodes of symptomatic hypoglycemia while on the bionic pancreas, and no episodes of severe hypoglycemia were associated with the system.

The system performed even better during the overnight period, when the risk of hypoglycemia is particularly concerning. “Patients with type 1 diabetes worry about developing hypoglycemia when they are sleeping and tend to let their blood sugar run high at night to reduce that risk,” explains Russell, an assistant professor of Medicine at Harvard Medical School. “Our study showed that the bionic pancreas reduced the risk of overnight hypoglycemia to almost nothing without raising the average glucose level. In fact the improvement in average overnight glucose was greater than the improvement in average glucose over the full 24-hour period.”

Damiano, whose work on this project is inspired by his own 17-year-old son’s type 1 diabetes, adds, “The availability of the bionic pancreas would dramatically change the life of people with diabetes by reducing average glucose levels – thereby reducing the risk of diabetes complications – reducing the risk of hypoglycemia, which is a constant fear of patients and their families, and reducing the emotional burden of managing type 1 diabetes.” A co-author of the Lancet report, Damiano is a professor of Biomedical Engineering at Boston University.

The BU patents covering the bionic pancreas have been licensed to Beta Bionics, a startup company co-founded by Damiano and El-Khatib. The company’s latest version of the bionic pancreas, called the iLet, integrates all components into a single unit, which will be tested in future clinical trials. People interested in participating in upcoming trials may contact Russell’s team at the MGH Diabetes Research Center in care of Llazar Cuko (LCUKO@mgh.harvard.edu ).

Here`s a link to and a citation for the paper,

Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial by Firas H El-Khatib, Courtney Balliro, Mallory A Hillard, Kendra L Magyar, Laya Ekhlaspour, Manasi Sinha, Debbie Mondesir, Aryan Esmaeili, Celia Hartigan, Michael J Thompson, Samir Malkani, J Paul Lock, David M Harlan, Paula Clinton, Eliana Frank, Darrell M Wilson, Daniel DeSalvo, Lisa Norlander, Trang Ly, Bruce A Buckingham, Jamie Diner, Milana Dezube, Laura A Young, April Goley, M Sue Kirkman, John B Buse, Hui Zheng, Rajendranath R Selagamsetty, Edward R Damiano, Steven J Russell. Lancet DOI: http://dx.doi.org/10.1016/S0140-6736(16)32567-3  Published: 19 December 2016

This paper is behind a paywall.

You can find out more about Beta Bionics and iLet here.

Artificial pancreas in 2018?

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According to Dr. Roman Hovorka and Dr. Hood Thabit of the University of Cambridge, UK, there will be an artificial pancreas assuming issues such as cybersecurity are resolved. From a June 30, 2016 Diabetologia press release on EurekAlert,

The artificial pancreas — a device which monitors blood glucose in patients with type 1 diabetes and then automatically adjusts levels of insulin entering the body — is likely to be available by 2018, conclude authors of a paper in Diabetologia (the journal of the European Association for the Study of Diabetes). Issues such as speed of action of the forms of insulin used, reliability, convenience and accuracy of glucose monitors plus cybersecurity to protect devices from hacking, are among the issues that are being addressed.

The press release describes the current technology available for diabetes type 1 patients and alternatives other than an artificial pancreas,

Currently available technology allows insulin pumps to deliver insulin to people with diabetes after taking a reading or readings from glucose meters, but these two components are separate. It is the joining together of both parts into a ‘closed loop’ that makes an artificial pancreas, explain authors Dr Roman Hovorka and Dr Hood Thabit of the University of Cambridge, UK. “In trials to date, users have been positive about how use of an artificial pancreas gives them ‘time off’ or a ‘holiday’ from their diabetes management, since the system is managing their blood sugar effectively without the need for constant monitoring by the user,” they say.

One part of the clinical need for the artificial pancreas is the variability of insulin requirements between and within individuals — on one day a person could use one third of their normal requirements, and on another 3 times what they normally would. This is dependent on the individual, their diet, their physical activity and other factors. The combination of all these factors together places a burden on people with type 1 diabetes to constantly monitor their glucose levels, to ensure they don’t end up with too much blood sugar (hyperglycaemic) or more commonly, too little (hypoglycaemic). Both of these complications can cause significant damage to blood vessels and nerve endings, making complications such as cardiovascular problems more likely.

There are alternatives to the artificial pancreas, with improvements in technology in both whole pancreas transplantation and also transplants of just the beta cells from the pancreas which produce insulin. However, recipients of these transplants require drugs to supress their immune systems just as in other organ transplants. In the case of whole pancreas transplantation, major surgery is required; and in beta cell islet transplantation, the body’s immune system can still attack the transplanted cells and kill off a large proportion of them (80% in some cases). The artificial pancreas of course avoids the need for major surgery and immunosuppressant drugs.

Researchers are working to solve one of the major problems with an artificial pancreas according to the press release,

Researchers globally continue to work on a number of challenges faced by artificial pancreas technology. One such challenge is that even fast-acting insulin analogues do not reach their peak levels in the bloodstream until 0.5 to 2 hours after injection, with their effects lasting 3 to 5 hours. So this may not be fast enough for effective control in, for example, conditions of vigorous exercise. Use of the even faster acting ‘insulin aspart’ analogue may remove part of this problem, as could use of other forms of insulin such as inhaled insulin. Work also continues to improve the software in closed loop systems to make it as accurate as possible in blood sugar management.

The press release also provides a brief outline of some of the studies being run on one artificial pancreas or another, offers an abbreviated timeline for when the medical device may be found on the market, and notes specific cybersecurity issues,

A number of clinical studies have been completed using the artificial pancreas in its various forms, in various settings such as diabetes camps for children, and real life home testing. Many of these trials have shown as good or better glucose control than existing technologies (with success defined by time spent in a target range of ideal blood glucose concentrations and reduced risk of hypoglycaemia). A number of other studies are ongoing. The authors say: “Prolonged 6- to 24-month multinational closed-loop clinical trials and pivotal studies are underway or in preparation including adults and children. As closed loop devices may be vulnerable to cybersecurity threats such as interference with wireless protocols and unauthorised data retrieval, implementation of secure communications protocols is a must.”

The actual timeline to availability of the artificial pancreas, as with other medical devices, encompasses regulatory approvals with reassuring attitudes of regulatory agencies such as the US Food and Drug Administration (FDA), which is currently reviewing one proposed artificial pancreas with approval possibly as soon as 2017. And a recent review by the UK National Institute of Health Research (NIHR) reported that automated closed-loop systems may be expected to appear in the (European) market by the end of 2018. The authors say: “This timeline will largely be dependent upon regulatory approvals and ensuring that infrastructures and support are in place for healthcare professionals providing clinical care. Structured education will need to continue to augment efficacy and safety.”

The authors say: “Cost-effectiveness of closed-loop is to be determined to support access and reimbursement. In addition to conventional endpoints such as blood sugar control, quality of life is to be included to assess burden of disease management and hypoglycaemia. Future research may include finding out which sub-populations may benefit most from using an artificial pancreas. Research is underway to evaluate these closed-loop systems in the very young, in pregnant women with type 1 diabetes, and in hospital in-patients who are suffering episodes of hyperglycaemia.”

They conclude: “Significant milestones moving the artificial pancreas from laboratory to free-living unsupervised home settings have been achieved in the past decade. Through inter-disciplinary collaboration, teams worldwide have accelerated progress and real-world closed-loop applications have been demonstrated. Given the challenges of beta-cell transplantation, closed-loop technologies are, with continuing innovation potential, destined to provide a viable alternative for existing insulin pump therapy and multiple daily insulin injections.”

Here’s a link to and a citation for the paper,

Coming of age: the artificial pancreas for type 1 diabetes by Hood Thabit, Roman Hovorka. Diabetologia (2016). doi:10.1007/s00125-016-4022-4 First Online: 30 June 2016

This is an open access paper.

Parvus Therapeutics (Calgary, Canada) and reprogramming immune cells

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An international collaboration of Canadian, Spanish, and US scientists has announced a new therapeutic approach which could reverse autoimmune diseases in a Feb. 17, 2016 news item on Nanotechnology Now,

• Nanotechnology Approach Restores Glucose Regulation and Motor Function in In Vivo Preclinical Models of Diabetes and Multiple Sclerosis, Respectively; Joint Swelling and Destruction Resolved in In Vivo Model of Rheumatoid Arthritis
• Parvus’ Approach Can Be Tailored to Treat Diverse Diseases

A Feb. 17, 2016 Parvus Therapeutics news release (also on EurekAlert), which originated the news item, provides more detail and a strong orientation to marketing communication,

Parvus Therapeutics today announced the publication in Nature of a seminal paper describing the discovery and applications of a novel therapeutic approach employing nanomedicines, referred to as “Navacims”TM, to reprogram white blood cells to become regulatory cells capable of blunting autoimmune responses and restoring the equilibrium of the immune system. Navacims are nanoparticles (NPs) coated with disease-relevant peptide-major histocompatibility complexes (pMHCs) that alter the behavior of pathogenic T lymphocytes by binding directly to their antigen receptors. The peer-reviewed article, titled “Expanding antigen-specific regulatory networks to treat autoimmunity” reports on a body of work, including results in multiple in vivo disease models, built on more than eight years of research by Parvus Founder and Chief Scientific Officer, Pere Santamaria, M.D., Ph.D.

Dr. Santamaria commented, “Autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, are extraordinarily complex responses of our immune system against some of our own tissues (e.g. pancreas, brain and joints, respectively), leading to chronic organ inflammation, organ dysfunction, and, in some cases, premature death. Blunting these incompletely understood immune responses without suppressing the normal components of our immune system that protect us against infection and cancer is not currently possible.”

“However, our work offers a pharmaceutical solution to this fundamental problem,” Dr. Santamaria continued. “Navacims essentially re-program disease-causing white blood cells to become disease-suppressing cells, known as regulatory cells, leading to sustained therapeutic effects in various spontaneous and experimental autoimmune diseases, as reported in our article in Nature. Essentially, we have found that Navacims can be tailored to treat a wide range of autoimmune diseases, while sharing a common structure. Importantly, they have been shown to affect human white blood cells in the same manner as they do murine cells. Furthermore, Navacims have shown promising safety findings in preclinical in vivo models. Based on our results to date, we believe Navacims represent a therapeutic platform with broad-ranging health care implications.”

Findings being reported in Nature include:

pMHC class II Navacims expanded cognate CD4+ T-cells that consistently have a TR1-like, regulatory T cell surface phenotype, transcriptional pattern and cytokine profile (mouse=human TR1 cells) systemically.

pMHC class II-Navacims designed to target T cells in newly diabetic nonobese (NOD) mice restored normoglycemia (normal blood sugar regulation) in the majority of the mice tested.

Tailored pMHC class II Navacims restored motor function to paralyzed C57BL/6 mice at the peak of Experimental Autoimmune Encephalomyelitis (a model of Multiple Sclerosis).

pMHC class II Navacims, targeting disease-causing T cells in joints, resolved joint swelling and destruction in arthritic mice.

“The findings being reported in Nature represent a scientific advance for Parvus and also a major achievement in the field of Immunology,” said Janice M. LeCocq, CEO of Parvus. “We believe that Dr. Santamaria’s work has the potential to transform the treatment of many of the more than 80 major autoimmune diseases affecting humankind, alleviating the suffering of millions of patients and their families. Over the coming year, we will be dedicating much of our in-house efforts to the advancement of our two lead programs for type 1 diabetes and multiple sclerosis.”

“Dr. Santamaria’s work to target the immune system dysfunction that causes type 1 diabetes represents the kind of innovative work that JDRF believes will eventually get us to a cure for this disease,” said Juvenile Diabetes Research Foundation Vice President of Discovery Research Julia Greenstein, Ph.D. “He and his colleagues have made exciting progress towards possibly developing a new class of drugs that could rebalance certain T-cells and ultimately provide a cure for type 1 diabetes and other autoimmune diseases as well.” The JDRF has funded the work of Dr. Santamaria and his colleagues at Parvus to explore Navacim-based treatments for diabetes.

Parvus’ strategy is to establish partnerships with major pharmaceutical companies to undertake the clinical and commercial development of many of its product pipeline candidates while also reserving rights to others suitable for its own development and commercialization. Parvus currently is engaged in late stage discussions with multiple pharmaceutical companies with regard to the type 1 diabetes (T1D) program. Manufacturing scale-up is now underway to supply upcoming preclinical and clinical studies.

The work being reported in Nature was led by Dr. Pere Santamaria and largely executed at the University of Calgary, Cumming School of Medicine (animal models of disease) and the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (humanized mouse work), with significant contributions from investigators at Institutions in Europe and the US. Further, Innovate Calgary, the technology-transfer and business-incubation center for the University of Calgary, provided early support for the transfer of the Navacims technology to and incubation of Parvus Therapeutics, which was organized as a separate entity in 2012.

It should be noted that this intervention has been tested on ‘humanized’ mice and, at this point, there don’t seem to have been any human clinical trials. At a guess I’d say we’re still several years away from this therapeutic intervention reaching the market, should it prove to be successful in humans.

Here’s a link to and a citation for the paper,

Expanding antigen-specific regulatory networks to treat autoimmunity by Xavier Clemente Casares, Jesus Blanco, Poornima Ambalavanan, Jun Yamanouchi, Santiswarup Singha, Cesar Fandos, Sue Tsai, Jinguo Wang, Nahir Garabatos, Cristina Izquierdo, Smriti Agrawal, Michael B. Keough, V. Wee Yong, Eddie James, Anna Moore, Yang Yang, Thomas Stratmann, Pau Serra, & Pere Santamaria. Nature (2016) doi:10.1038/nature16962 Published online 17 February 2016

This paper is behind a paywall.