Anti-Mitochondrial Antibodies in Autism – A Marker for Treatment?

Recent focus on new treatments for Autistic Spectrum disorders have zeroed in heavily on the immune component of this disease. Physicians around the world are becoming more and more convinced that Autism may be triggered by some autoimmune process leading to damage of the body’s own neurological system.

Quite a few studies have pointed to aberrant immune markers found more commonly in autistic children compared to normal healthy children, but most of these markers have never made it to the masses, instead their access was strictly for research.
However that now has changed.

A few years ago researchers discovered that a protein called Neurotensin was found extremely elevated in Autistic Children. They showed that this peptide released mitochondrial DNA into the extracellular space (outside the cell), which acted as an autoimmune trigger.

The mitochondria is basically the “power house” of the cell. If its function becomes abnormal, the cells no longer have the energy to function properly, thus leading to either cell death or severely limited function. Either way the cells with the damaged mitochondrial don’t function well. Neurons are very sensitive to mitochondrial damage, having a smaller amount compared to other cells requiring large amounts of energy, such as muscles.

The mitochondria has its own DNA content separate from our own cells. If this mitochondrial DNA was released somehow into the extracellular space, the body would then react to it as if it was foreign, like a virus or bacterial, creating an immune response. Well that’s exactly what Neurotensin was causing. Studies showed that when Neurotensin was elevated mitochondrial DNA was found outside in the extracellular space.

Recently in the Journal of Neuroinflammation researchers took it a step further. Since Neurotensin is not commercially available they decided to test markers that were. They also wanted to determine if this extracellular mitochondrial DNA was actually causing an immune response. This way parents may be able to definitely decide if their child’s immune system was attacking the mitochondria.

Enter anti-mitochondrial antibody type II, a marker used for primary biliary chirrosis.

Researchers found that this antibody was significantly elevated in Autistic children as compared to children not affected with Autism, effectively demonstrating that many children suffering from Autism were reacting to their own mitochondria. They postulated that this reaction was affecting multiple aspects of the immune system, laying the ground work for potential damage or excessive inflammation.

This is a great study, showing a possible cause and effect process. Anti-mitochondrial antibody is available to test for, with most insurance companies covering it.

If your child has never been tested for the antibody, it may be worthwhile to have your physician order it. Having knowledge that maybe your child is suffering an autoimmune process is huge. It definitely will be a marker I use and will change how I treat my patients.

About Antibodies for Cancer Prevention

The latest discoveries in medical technology are using certain antibodies for cancer prevention. These medical miracles are called monoclonal antibodies, or “Mabs”, and can be used to help ward off all kinds of cancers. The technology to aid doctors and nurses fight cancer has only come about within the last several decades. Further research continually turns up more and more Mabs, providing hope for those who have already developed cancer and for those who are trying to protect themselves from it.

The American Cancer Society’s (AMC) web site explains that monoclonal antibodies were first developed in laboratories using mice with myeloma cells, which is a kind of bone marrow cancer, and mice that produced specific antibodies for those cells. The combination of these two cells, called a hybridoma cell, forces a perpetual factory making antibodies. The antibodies end up being identical clones of the original hybridoma cell, which is why they are called monoclonal antibodies. The problem scientists faced with this phenomenal finding was that human antibodies recognized the mouse-produced antibodies as foreign invaders and attacked them. With hard work and dedication, scientists are continuing to develop ways to integrate human antibodies in lieu of mouse antibodies so cancer patients will be able to use the immunotherapy as a form of treatment.

Today there are two types of Mabs, naked and conjugated. The difference between these two lies in the fact that naked antibodies lack radioactive materials attached to them. Conjugated antibodies, on the other hand, are fused with a chemotherapy drug or other toxin used to fight off cancer cells. In recent years the Food and Drug Administration (FDA) has approved several Mabs, both naked and conjugated, for cancer treatments. A list of approved Mabs is available through the ACA’s web site. In 2004 and in 2006, Bevacizumab, a naked antibody, was approved for treating certain types of breast cancers. In 2001 the FDA approved the use of Alemuzumab, a naked antibody, which acts as a form of leukemia prevention by attaching itself to both B and T cancer cells, causing the body’s immune system to attack and kill them. In 2000, the FDA approved the use of a conjugated antibody, Gemtuzumab ozogamicin, which is used in the treatment of chronic leukemia.

If you have lost someone to cancer or know someone suffering from cancer, it is not hard to understand how crucial medical research is when it comes to finding antibodies for cancer prevention. The number of cancer victims continues to rise each year, hitting people of all ages. With the prolonged use and approval of Mabs, these numbers may begin to decline, alleviating the fear everyone has about developing some form of the deadly disease. Diet and exercise will only help an individual a certain amount, leaving genetics and medical breakthroughs to do the rest. By continuing to fine tune more variations of antibodies for cancer prevention, medicine as we know it today could be changed for the better in years to come.

Medicine has come a long way in the last fifty years thanks to the help of scientists and research laboratories. Their combined efforts have aided individuals all over the world prevent and treat life-threatening forms of cancer. Advancements in immunotherapy treatments that use antibodies for cancer prevention, combined with other cancer-deterring methods, are just a step on the threshold for greater triumphs to help everyone live long and healthy lives.

Sclerostin Antibody – Bone Overgrowth From Mutations

Sclerostin antibody Sclerostin is a secreted glycoprotein with a protein sequence similar to the bone morphogenic protein antagonist family. The protein is encoded by the SOST gene in humans. It is produced by the osteocyte and down regulates osteoblastic bone formation.

Recently, sclerostin has been implicated in the inhibition of Wnt signaling leading to attenuated bone formation and growth, acting as a stop signal to decrease bone formation by osteoblasts. Mutations in sclerostin are a result from early stop signals during protein production, leading to uninhibited Wnt signaling and bone overgrowth. The mutations in this process can lead to a range of diseases, such as type II diabetes, breast and prostate cancer.

Production of this protein is inhibited by parathyroid hormone, leading to enhanced release of the calcium from the large reservoir contained in the bones, indirectly stimulating bone resorption by osteoclasts, and various other cytokines. Production of this protein is stimulated by calcitonin, a hormone which acts to reduce blood calcium levels that acts in opposition to the parathyroid hormone.

Bone remodelling is the process by which the adult skeleton is continually renewed through the highly coordinated activity of three types of cells, which are osteoclasts, osteoblasts, and osteocytes. Disruptions in signalling among these cells and alterations in their activity have been associated with skeletal diseases such as ‘van Buchem disease’.

Mutations in the sclerostin gene are associated with the autosomal-recessive disorder called sclerosteosis, in addition to other disorders characterized by bone overgrowth. Sclerosteosis is a rare disorder characterized by bone over growth primarily in the skull, mandible and long, tubular bones. Individual affected with this homozygous disorder have no detectable levels of circulating sclerostin. However, heterozygous individuals for the mutations express the normal phenotype and normal lifespan, with dense bones and a low risk for fracture. This observation has led to the development of a novel strategy to emulate the heterozygous mutational state as an effective treatment for bone loss disorders such as osteoporosis.

Sclerostin is the subject of key research into both bone overgrowth and bone loss. As Sclerostin antibody could potentially increase bone formation significantly without effecting bone resorption and enhance bone strength. Thus, sclerostin antibody can potentially alleviate osteoporosis disease, this occurs when bones become fragile and more likely to fracture.

This has been established in numerous clinical trials in rats, monkeys, and in humans. It has been recognized that the absence of the sclerostin protein leads to bone overgrowth. Whereas an excess amount of sclerostin leads to bone loss and reduced bone strength. This was proved in various trials, for instance the trial on a six month old female rats was a success. Once the sclerostin antibody was administered, it quickly created an increase in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. For the human clinical trials, it was a success in healthy men and postmenopausal women (72 targets), as the antibody was tolerated well, which was the palpable primary goal. Additionally, the targets had augmented bone density for hip fractures and in their spine. Methods to increase bone in humans have long been sought. The bone formation axis controlled by sclerostin may provide an important new strategy to accomplish this. Thus, Sclerostin asserts itself as a prime therapeutic target to address bone disorders. The modification of its activity or expression offers an exciting possibility for the development of new drugs for the treatment of disorders associated with bone loss.

This antibody is for research use only and can be used on the following applications, WB (western blot), IHC-P(immunohistochemistry), and P-ELISA.