A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine.  Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact,  preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.

Dr. Michael Mullan M.D., Ph.D
President & CEO
Roskamp Institute
Preliminary results of the treatment of a mouse model of Multiple Sclerosis with Anatabine. Roskamp Institute scientists Dr. Michael Mullan and Dr. Daniel Paris used a standard model of MS (multiple sclerosis) to assess the effects of anatabine in this disease characterized by very high levels of inflammation in the brain. The mouse model known as EAE (experimental autoimmune enchephalomyelitis) is characterized by high levels of circulating antibodies to the fatty sheaths that surround nerve fibers. The model is induced by vaccinating mice with myelin which induces an autoimmune reaction. As a consequence there is a devastating inflammatory process in the brain which has the effect of destroying neurons and causing progressive paralysis. In this regard the disease model looks very similar to that which occurs in human MS. Treatment with anatabine resulted in a dramatic reduction in the rate of paralysis of hind limbs.
Dr. John L. Faessel


Commentary and Insights

Report from the Harvard Club Meeting

Dr. Mullan and the Roskamp Institute have conducted research relating to the company's anatabine compound for a number of years. Dr. Mullan first spoke to and thoroughly reprised with the supporting graphs the research that the Roskamp Institute has performed, essentially what he presented last June at a Roskamp Institute meeting. Mullan again played the videos that showed standard Alzheimer's-afflicted mice beginning not only to remember again, but becoming able to add critical new information to the cognitive equation and, thus, to change behavior so as even to improve their lot after the administration of anatabine. That's impossible for a "demented" mouse. A split screen video depicted for comparison a mouse fully impaired with the disease. He went on to say that CRP* levels also fell 50% in these test animals, indicating less inflammation. Dr. Mullan called the research "profound."  For more details of the articles please visit: http://seekingalpha.com/instablog/576542-dr-john-faessel/618891-report-from-the-harvard-club-meeting-re-cigx-snowballing-progress