Yesterday we considered some interesting Alzheimer’s Disease research findings. In other AD related research the conclusion was reached that prevention is easier than cure. I am sometimes amazed that what appears to be such an obvious principle can feature as a conclusion expressed with such profundity, as though it were a new concept.
This is the conclusion reached in a study by Todd E. Golde at Mayo Clinic Jacksonville, Florida, USA. The research results will be published in the January 2006 issue of the Journal of Clinical Investigation. The study is titled: Anti-Abeta42 and Anti-Abeta40-specific monoclonal antibodies attenuate amyloid deposition in an Alzheimer disease mouse model.
Current hypotheses suggest that it is the accumulation over time of amyloid beta peptide 1-42 (Abeta42) that triggers changes in the brain that lead to cognitive dysfunction in Alzheimer’s disease. The reduction of amyloid levels is therefore a major therapeutic objective. Todd Golde and colleagues from the Mayo Clinic Jacksonville report evidence to suggest that prevention of amyloid deposition may be easier than curing established Alzheimer’s disease.
The authors use transgenic mice genetically predisposed to accumulate amyloid deposits in their brain to show that an immunization strategy targeting Abeta42, or a second form of Abeta known as Abeta40, prevents the onset of amyloid deposition in these mice at a young age. In contrast, the anti-Abeta42 or anti-Abeta40 monoclonal antibodies were not effective in altering Abeta deposition in mice with modest levels of preexisting Abeta deposits, nor were they capable of clearing existing deposits. The results suggest that it may be easier to prevent Abeta deposition than to alter Abeta once deposited.
This method may be an effective strategy to prevent amyloid deposition prior to the onset of Alzheimer’s disease, but may have limited benefit in a therapeutic setting where amyloid deposits are already well established within the brain.
Again, one has to ask why the adverse deposits happen in the first place. Understanding of the cause can be achieved at many levels. Golde’s research is one way. I am interested in a more fundamental understanding. Certainly, as I suggested yesterday, maintaining a clean, non-toxic cellular environment through healthy living, a suitable diet (certainly devoid of junk food and highly refined products) and occasional cleansing is a very wise approach to take.
New research from the Gladstone Institute of Neurological Disease (GIND) details exactly how a mutant form of the protein apolipoprotein E, also known as apoE, is a causative factor for Alzheimer’s disease.
It pinpoints mitochondria, the organelles within cells designed to turn glucose into energy, as a key site that specific fragments of a particular form of apoE attack, leading to the neuronal death characteristic of Alzheimer’s disease (AD).
The findings were published by the Proceedings of the National Academy of Science in the December 20, 2005, issue of PNAS.
According to Gladstone Assistant Investigator Yadong Huang, MD, PhD, who headed the study, it has been known for several years that a correlation exists between lowered glucose metabolism and the presence in the brain of a mutant form of a protein that transports cholesterol.
Scientists have been unable to determine if this mutant protein actually interferes with the ability of neurons to make use of glucose in the brain, but they have theorized that such an inability to access glucose might kill off crucial brain cells, causing AD symptoms.
The devastating effects of AD are well known: progressive and inexorable loss of cognitive function that erases memories, extinguishes personality, and robs people of their ability to think, reason and carry out the activities of everyday life. Despite intensive efforts to identify the underlying causes, and considerable progress in unraveling the web of contributing factors, the pathogenesis of AD remains tantalizingly elusive, and a cure is still out of reach, says Huang.
Seeking answers to a fundamental question in AD research on what actually causes brain cells to die in affected patients, Huang and his scientific team pursued a particularly promising avenue of research over the last few years. Their efforts focused on apoE, a protein comprised of 299 amino acids whose apoE4 isoform has been known for the last decade to be the most significant genetic risk factor for AD.
"Several years ago, we found that apoE is subject to cleavage that results in fragments that are toxic to neurons," says Huang, who also is assistant professor of pathology and neurology at UC San Francisco. "This study shows which parts of apoE are toxic and gives hints as to the site of its action."
The research team investigated the cellular and molecular mechanisms of the neurotoxicity caused by apoE4 fragments, performing a series of studies in cultured mouse neuronal cells. The cells expressed apoE fragments of various lengths and with mutations designed to enable the investigators to determine precisely which portions of the fragment–that is, which of apoE4’s 299 amino acids–are responsible for its detrimental effects.
Research findings showed that fragments containing both the lipid- and receptor-binding regions, but lacking the C-terminal 27 amino acids (273-299), were found to be neurotoxic. The toxic fragments appear in the mitochondria, where they impaired membrane integrity and mitochondrial function.
"Blocking interaction of apoE4 fragments with the mitochondria is a potential new strategy for inhibiting the detrimental effects of apoE4 in AD and other neurological diseases," Huang explains.
"Alzheimer’s disease is a complex condition," says co-author Robert W. Mahley, MD, PhD, president of the Gladstone Institutes and UCSF professor of pathology and medicine. "Many factors seem to be involved, and all need to be explored to help us find a way to combat this terrible disease. We are very excited about these particular results because they point to a new and potentially valuable therapeutic strategy."
This work was supported in part by the National Institutes of Health and by a research grant from GlaxoSmithKline.
Thanks to John Watson from the Institute for the above report. GIND is affiliated with UCSF, a university that contributes to health care by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care. For further information, visit http://www.gladstone.ucsf.edu.
As interesting as this research is, I can’t bring myself to be too excited about it. In part this is because I think the rigidly orthodox thinking, as clever as it is, remains ordinary, predictable and lacking in creativity. It may move us towards development of a drug by GlaxoSmithKline in time perhaps, but cure or prevention are not yet on the horizon. Any drug resulting from these endeavours may or may not be significantly useful but it will most definitely have an associated downside.
Alzheimer’s disease (AD) is a degenerative disorder and ultimately another of the lifestyle diseases. While whole populations pursue unhealthy lifestyles, in polluted external environments, generating polluted and toxic internal cellular environments, AD will continue to plague us.
Further burdening the cells with more toxic drugs is not the solution. However, for those who leave it too late to remedy their lifestyle, even a bad drug may be welcomed. Perhaps this research will hasten the availability of a product that can relieve some of the suffering associated with AD.
I just read an article extolling the virtues of setting some worthwhile personal health goals for 2006. It was written by Jon Herring, Health Editor, Early To Rise and it made several good points. I don’t want to abuse the privilege of having access to Jon’s article but I will share part of one paragraph with you. It’s a real gem.
My ultimate long-term health goal is simple: I want to enjoy a healthspan that is equal to my lifespan. In other words, I intend to remain strong, active, and mentally sharp until the day I die of natural causes. To do that, I will make the choices throughout my life that will help prevent the diseases that are largely related to lifestyle – like cancer, heart disease, and diabetes.
A "healthspan", what a great concept, don’t you think? It sums up what many of us try to actively promote — stay really healthy for your entire life. For me, being healthy isn’t about not being sick. That’s just way too negative. Being healthy is about enjoying life to the full.
When your life is gone, it’s gone. You can’t get it back. Why waste it being less than optimally well?
One other thing Jon promotes is making your health goals achievable within 6 weeks. Great idea. Who sticks to resolutions that are supposed to last a whole year? Not many, that’s for sure. But 6 weeks, well just go for it. Give it everything. Really make significant improvements in your health. In 6 weeks time you can set some more and by then you’ll find new motivation flowing from the very improvements you will already be enjoying.
So don’t settle for under-living. Get going, build your health and enjoy more of life.
The FDA and GlaxoSmithKline have advised health professionals and patients of new adverse findings associated with the use of Avandia and Avandamet, used in the treatment of type 2 diabetes. The FDA notice says:
Avandia (rosiglitazone maleate)
Avandamet (rosiglitazone maleate/metformin HCl)
Audience: Endocrinologists, other healthcare professionals and patients
[Posted 01/05/2006] GlaxoSmithKline and FDA notified healthcare professionals about post-marketing reports of new onset and worsening diabetic macular edema for patients receiving rosiglitazone. In the majority of these cases, the patients also reported concurrent peripheral edema. In some cases, the macular edema resolved or improved following discontinuation of therapy and in one case, macular edema resolved after dose reduction.
The company certainly reported its findings, as it must, but seeks to keep them in perspective, or minimize their significance, depending on your point of view. You can see this in the statistics reported in the following letter.
Dear Health Care Provider,
As part of the ongoing efforts of GlaxoSmithKline (GSK) to provide updated information to health care providers, we would like to inform you of important new safety information regarding products containing rosiglitazone (i.e., Avandia®, Avandamet®, and coming soon in some markets, Avandaryl). These products are anti diabetic therapies used in treating type 2 diabetes mellitus. To date, cumulative worldwide exposure is in excess of 5.3 million patients for Avandia and 769,000 patients for Avandamet.
GlaxoSmithKline has received very rare post-marketing reports of new onset and worsening diabetic macular edema for patients receiving rosiglitazone (Avandia or Avandamet). In the majority of these cases, the patients also reported concurrent peripheral edema. In some cases, the macular edema resolved or improved following discontinuation of therapy and in one case, macular oedema resolved after dose reduction.
Macular edema typically occurs in association with diabetic retinopathy, although it is more likely to occur as retinopathy progresses. Risk factors for macular edema include duration of diabetes, presence of retinopathy, hypertension, and poor glycemic control. Symptoms suggestive of macular edema include blurred or distorted vision, decreased color sensitivity, and decreased dark adaptation.
GSK is sending this letter in order to highlight this important new safety information and the precaution proposed by the company to be included in all rosiglitazone (i.e., Avandia, Avandamet and coming soon in some markets, Avandaryl) product information for prescribers and patient information leaflets.
GlaxoSmithKline is committed to providing Health Care Providers and patients with the most up-to-date and accurate information regarding our products. Should you have any questions or require additional information, please contact your local GSK information line.
Sincerely,
Alexander R. Cobitz, M.D., Ph.D.
Senior Director Metabolism
Clinical Development and Medical Affairs
GlaxoSmithKline
I encourage people with Type 2 diabetes to seriously consider consulting a naturopathic doctor. Until people are willing to make appropriate lifestyle changes, especially dietary and exercise related, we will continue to see large numbers suffering with this disease.
In the vast majority of cases the condition is completely avoidable. It is certainly treatable without dependence on highly toxic drugs.
Here is a document titled "An Open Letter to Mankind" by Dr Iain MacRobert.
In the last twenty years, a huge and growing body of research has been carried out into the role of the sugars that are an essential part of glycoproteins. These sugar-protein complexes are the building blocks of our immune system, and are the method by which cells "talk" to each other. Research now runs to over 80,000 papers in many established medical journals. The accompanying papers in this pack discuss various aspects of sugar metabolism, from the scientific research to case histories, along with doctors own experience with the amazing healing qualities of these glyconutrients.
(Note: There are over 200 sugars found in nature – only 8 have been deemed "essential" – the common table sugar is one we all get way too much of in our diet and is NOT one of the sugars that is deemed "essential". )
It has been conclusively shown that there are 8 essential sugars (out of the 200), and 6 are missing from our modern Western diet. This lack is caused by soil depletion, early picking of vegetables and fruits, processing of foods, and pollution. We all now face a very toxic environment, and we now lack the very things we need to cope with the toxic load.
When these "essential" sugars are missing, the cells either cannot "talk", or they mis-communicate. The result is disease. Yes it is true, our cells can make these sugars from glucose, but this is a very metabolically expensive process. It has been shown that dietary lack results in defective immune response, either too much or too little. Allergic conditions are examples of an over reactive immune system. An under reactive immune system could result in an inability of the natural "killer" cells (lymphocytes) to recognize diseased or cancerous cells, and dispose of them. The results of that may mean the death of the person! When the cells are given the nutrients they need, and begin to function properly, the resultant health benefits range from profound to amazing. In some cases, the so called laws of medical science have been overturned. I have spoken to people who had (past tense) multiple sclerosis, and who now do not have it. Their neurological lesions have disappeared from the MRI scan. To a natural skeptic like myself, the implication of this reversal was simple – medicine is now facing the need for a total paradigm shift in its thinking, as deep a shift as that which occurred when bacteria were first shown to be the agents of infectious diseases.
As doctors, I believe we need to move from a "curative" view to a "wellness" view of what we do. Whilst modern medicine has made great strides in many areas, doctors, myself included, feel somewhat helpless when attempting to deal with the flood of degenerative disease and chronic illness that are the mark of our generation. All we can offer are drugs with very serious, and in some cases, life threatening side effects. In the year 2000, more than 100,000 people died from the effects of properly prescribed, properly administered pharmaceutical agents in the United States alone. This does not count the tragic accidents of improperly used medication.
Are these sugars safe? Well, they are food, not drugs. They have NO toxic or side effects. Five of the eight are found in human breast milk, (one of the reasons why babies are protected from disease by breast feeding). The sugars are not pharmaceutical agents, and do not cure anything. They simply restore basic cellular functions to normal, and then the body can fend for itself. The killer cells will work to identify and destroy diseased or cancerous cells. The immune system can be restored to normal to modulate itself in response to attack.
I believe that we are going to see this profound change in medical practice over the next few years. As usual, I predict that the medical profession will be dragged kicking and screaming into this change. Every major medical advance, from simple hand washing between patients, to using limes to treat scurvy, to smallpox vaccination, the introduction of anesthesia, and surgical asepsis, has been first ridiculed, then opposed, until finally acceptance came when the truth became totally self evident. This is happening today with glyconutrition. There are now over 1000 medical practitioners in the USA who regularly use glyconutrients in their practices. The AMA in Australia has just release a paper acknowledging the patient’s right to use complimentary medicine. That statement allows such things as acupuncture and yoga, techniques that may have benefit, but have no scientific validation. Compare that to the huge body of literature on glycoscience, including the 1999 Nobel Prize in Medicine. The case history data is growing into the tens of thousands of patients whose disease states have been improved, or in many cases eradicated, by the simple act of adding these sugars to the diet. This evidence will, in time, be overwhelming, and those who are skeptical and critical will be won over, by evidence that cannot be refuted. When you have CAT scan evidence of the lesions of multiple sclerosis disappearing, of metastatic carcinoma resolving, of the reversal of Alzheimer’s and Parkinson’s disease, of increase in IQ of Down’s syndrome children, along with positive effects in arthritis, infections, chronic fatigue syndrome, fibromyalgia, what can you say? These are case histories presented by medical professionals, not snake oil salesmen. They are medically verifiable.
I think you will find the accompanying papers interesting. I hope that they will increase your understanding, and help you on the road to optimal health. Further information can be had at the following internet site: http://www.glycoscience.org