Tuesday, October 26, 2010

New Finding May Aid Alzheimer’s Treatment Options

A protein recently found in the brain -- gamma secretase activating protein or GSAP -- increases the production of beta-amyloid, the presumed culprit in Alzheimer’s disease. In a mouse model, reducing GSAP led to reduced beta-amyloid disposition ( Nature, 2010, 467, pp 95-99.) This prompts in turn the appealing notion that a drug could be found to inhibit GSAP and thereby forestall or prevent the onset of Alzheimer’s disease.

Imatinib (Gleevec, used to treat chronic myelocytic leukemia or CML) does inhibit GSAP and, in laboratory models, reduces beta-amyloid creation. Unfortunately, imatinib does not cross the blood brain barrier so it cannot be used clinically. A search is now on for a compound that acts like imatinib yet can get into the brain. If found, it would be a very exciting discovery.

Tuesday, October 19, 2010

The Implications of Chronic Disease

I have written frequently about the importance of chronic illnesses. Most of us are just not aware that their incidence is rising - and rapidly. We tend to think instead about acute illnesses and injury but chronic illnesses are now not only common but last a lifetime once developed and are inherently expensive to treat. On top of that there are enormous losses in quality of life, personal productivity and economic impact on the individual and society.

The Milken Institute quantified some of these issues in a research report a few years ago. They evaluated cancer, diabetes [presumably type 2], hypertension, stroke, heart disease, pulmonary conditions and mental disorders. Here are some of the key findings:

• “More than 109 million Americans report having at least one of the seven diseases, for a total of 162 million cases.

• The total impact of these diseases on the economy is $1.3 trillion annually.

• Of this amount, lost productivity totals $1.1 trillion per year, while another $277 billion is spent annually on treatment.

• On our current path, in 2023 we project a 42 percent increase in cases of the seven chronic diseases.

• $4.2 trillion in treatment costs and lost economic output.

• Under a more optimistic scenario, assuming modest improvements in preventing and treating disease, we find that in 2023 we could avoid 40 million cases of chronic disease.

• We could reduce the economic impact of disease by 27 percent, or $1.1 trillion annually; we could increase the nation's GDP by $905 billion linked to productivity gains; we could also decrease treatment costs by $218 billion per year.

• Lower obesity rates alone could produce productivity gains of $254 billion and avoid $60 billion in treatment expenditures per year.”

To me the important point is that “each has been linked to behavioral and/or environmental risk factors that broad-based prevention programs could address.” Restated, we as individuals need to take responsibility for our own health. Not every illness is preventable, but a very large percentage are. It is up to us to eat a nutritious diet in moderation, exercise our bodies, seek ways to reduce chronic stress and avoid tobacco. These four steps would make a huge difference in our health and our lives.

Meanwhile, we each need to have a primary care physician and that physician needs to accept the responsibility to assist us with our prevention strategies and to coordinate our care should we develop a chronic illness. This will mean better health and much lower costs.

Friday, October 15, 2010

Encapsulated Pig Islet Cells For Diabetes Type 1 – A Trial

Here is a follow-up to the post on islet cell xenotransplantation for type 1 diabetes mellitus. A group in New Zealand has been studying the use of islet cells derived from pigs which have not been genetically modified. The cells are encapsulated to protect them from immune cells. The company reports that they are self regulating (meaning that they will produce insulin as needed based on the body’s blood sugar levels) and efficient at secreting the insulin produced into the patient’s body. The investigators report on one patient that is now nearly 10 years since transplantation with persistent functioning islet cells. Dr John Baker and Living Cell Technologies are conducting the human trial after having tested their product in multiple animal models. The material below, taken from the US National Institutes of Health Clinical Trials web site [http://tinyurl.com/2fmcnp6 ], was prepared by the company and its investigators:

“Intraperitoneal islet transplantation has the potential to ameliorate type 1 diabetes mellitus and avert the long-term consequences of chronic diabetes which cannot be achieved by conventional insulin treatment.

As donor human islets are not available in sufficient numbers, porcine islets are the best alternative source as they are recognised as the most physiologically compatible xenogeneic insulin-producing cells. Although the use of pig-derived cells raises the risk of xenotic infections, this can be minimised by obtaining cells from designated pathogen-free (DPF) animals bred in isolation and monitored to be free of specified pathogens. The worldwide experience to date in more than 200 patients who have received transplants of pig tissue has not demonstrated evidence of transmitted xenotic infections.

As animal-derived tissues have to be protected from immune rejection when transplanted into humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine islets are preferably transplanted without the use of immunosuppressive drugs which cause significant morbidity. To protect them from immune rejection, the islets can be encapsulated in alginate microcapsules which permit the inward passage of nutrients and glucose and the outward passage of insulin. Alginate-encapsulated porcine islets transplanted without immunosuppressive drugs have survived rejection for many months in animal studies, and have been retrieved from a diabetic patient over 9.5 years after intraperitoneal transplantation and shown to contain viable islets that stain positive for insulin.

DIABECELL® comprises neonatal porcine islets encapsulated in alginate microcapsules. DIABECELL® has been safely transplanted in healthy and diabetic mice, rats, rabbits, dogs and non-human primates. Following DIABECELL® transplants, the requirement for daily insulin was significantly reduced in diabetic rats and non-human primates.

The optimal dose and frequency of transplantation of the current DIABECELL® preparation for the treatment of type 1 diabetes in humans can only be determined in clinical trials. The intention of this phase I/IIa clinical trial is to obtain at least 52 weeks safety and preliminary efficacy data in type 1 diabetic patients following transplantation of a single low effective dose of DIABECELL® into the peritoneal cavity.”

The results of this study, still a few years off, will be of great interest to those whose diabetes is hard to control with standard insulin approaches.

Praise for Dr Schimpff

The craft of science writing requires skills that are arguably the most underestimated and misunderstood in the media world. Dumbing down all too often gets mistaken for clarity. Showmanship frequently masks a poor presentation of scientific issues. Factoids are paraded in lieu of ideas. Answers are marketed at the expense of searching questions. By contrast, Steve Schimpff provides a fine combination of enlightenment and reading satisfaction. As a medical scientist he brings his readers encyclopedic knowledge of his subject. As a teacher and as a medical ambassador to other disciplines he's learned how to explain medical breakthroughs without unnecessary jargon. As an advisor to policymakers he's acquired the knack of cutting directly to the practical effects, showing how advances in medical science affect the big lifestyle and economic questions that concern us all. But Schimpff's greatest strength as a writer is that he's a physician through and through, caring above all for the person. His engaging conversational style, insights and fascinating treasury of cutting-edge information leave both lay readers and medical professionals turning his pages. In his hands the impact of new medical technologies and discoveries becomes an engrossing story about what lies ahead for us in the 21st century: as healthy people, as patients of all ages, as children, as parents, as taxpayers, as both consumers and providers of health services. There can be few greater stories than the adventure of what awaits our minds, bodies, budgets, lifespans and societies as new technologies change our world. Schimpff tells it with passion, vision, sweep, intelligence and an urgency that none of us can ignore.

-- N.J. Slabbert, science writer, co-author of Innovation, The Key to Prosperity: Technology & America's Role in the 21st Century Global Economy (with Aris Melissaratos, director of technology enterprise at the John Hopkins University).