It's not rocket science…

Recently discovered protein shows promise in treating Alzheimer’s diesease

New research in humans shows that the FKBP52 protein may prevent the Tau protein from turning pathogenic, or from causing disease.  

The FKBP52 protein was discovered by Baulieu 20 years ago in its ability to block Tau protein accumulation, which is commonly seen in Alzheimer’s disease (AD)patients. Microtubules are the railways in the brain upon which cellular cargo is transported. In patients with AD, tau tangles formed by misfolded tau proteins may compromise the stability of the microtubules within the nerve cells leaving them damaged. Currently, the mechanism of Tau toxicity is unclear and there are no drug treatments targeting Tau.

Professor Etienne Baulieu and colleagues at Inserm (National Institute for medical research in France) have recently published results that for the first time demonstrate that the FKBP52 protein may prevent hyperphosphorylation, or over accumulation of Tau protein, a characteristic of Alzheimer’s disease.

Specifically, the results of this study demonstrate a direct correlation between high levels of hyperphosphorylated Tau protein and reduced levels of FKBP52, in brain cells from patients that had died following AD, compared to normal brain cells. This indicates that when FKBP52 is reduced in nerve cells of AD patients, disease causing Tau is free to accumulate and contribute to the degeneration of brain cells.

IOS Press BV (2012, March 20). New hope for treating Alzheimer’s Disease: A Role for the FKBP52 protein. ScienceDaily. Retrieved April 5, 2012, from     
Julien Giustiniani, Marlène Sineus, Elodie Sardin, Omar Dounane, Maï Panchal, Véronique Sazdovitch, Charles Duyckaerts, Béatrice Chambraud, Etienne-Emile Baulieu. Decrease of the Immunophilin FKBP52 Accumulation in Human Brains of Alzheimer’s Disease and FTDP-17. Journal of Alzheimer’s Disease, Volume 29, issue 2 (March 2012) [link]


Text Message From: Neighboring Bacteria

As means of communication increase between humans, such as text messaging and social media, bacteria and potentially human cells are communicating with each other to come up with a plan of action.  Researchers at Rice and Tel Aviv University have been investigating the pathways in which these cells communicate information about cell stress, the colony density, and possible plans of neighboring cells.  Research in this area could result in many medical applications.

José Onuchi, Ph. D., explained to Science Daily that “Using this form of cell-to-cell communication, colonies of billions or trillions of bacteria can literally reach a consensus on actions that impact people.”

Onuchi gave an example of a group of harmless bacteria gathering on the skin.  These bacteria may one day send chemical signals to each other and decide that there are enough of them to join together and cause an infection.  This network of infection causing bacteria is known as a biofilm. Biofilms are responsible for making many chronic diseases difficult to treat.  Urinary tract infections and cystic fibrosis are two examples of biofilms forming and causing treatment difficulties.

Bacillus subtilis has been the focus of the research to try to understand this network of communication.  B. subtilis is a bacterium found in the soil and responds to stressful environmental conditions by either turning themselves into spores or transforming into a competency state, which is protective state that won’t be harmed by the outside conditions. These two states allow the bacteria to survive in harsh or stressful situations.  In the spore state the bacteria discard half of their DNA into the environment and create a thick armor like shell that allows them to survive for years, but they are able to return to  normal bacteria.  The competency state is more for short term stressful situations. The risk with the competency state is if the conditions don’t improve quickly the bacterium could die before being able to change into a spore.

Onuchi explained that most bacteria will become spores in poor environmental conditions but about 1-2%  “see” that the other bacteria are becoming spores and choose to take some of their discarded DNA and enter competency.

Onuchi believes that the bacteria make their decisions on “game theory”, which is a concept used in math to analyze conflict and cooperation.  Onuchi explained to Science Daily “…the bacteria have to weigh the pros and cons of their decisions. The bacteria make a decision based not only on what it knows about its own stress and environment, but it also has to think about what the other bacteria might do.”

So how can research on bacteria living in the soil and their communication and decision making processes benefit the human population in anyway?  One answer: cancer treatment.

As the research progresses with the bacteria , human cells are becoming the main focus.  Onuchi is specifically looking at communication that could result in uncontrolled division and growth, AKA the cause of cancer.  One of the main causes of cancer is just that, the uncontrolled division and growth of cells.  The current thought is that similarly to the bacteria discussed earlier, the human cells may be chit-chatting amongst themselves and sending chemical signals to one another that cause the cancer to grow. Not only could this be the starting point of cancer, but could also explain the spreading of cancer to other parts of the body, also known as metastasis.

Onuchi described the medical treatment benefits of identifying this process to Science Daily.

“It would open the door to developing better drugs that have fewer side effects. For example, once we get a handle on this process, we might block the specific chemical messages that signal a tumor to grow, developing a medicine that wouldn’t affect other body processes, reducing or eliminating side effects.”

The researchers are hopeful, but like most growing areas of science, cannot make any promises based on their research.  The identifying of the possibility of this communication pathway and understanding the complexities of the bacteria communication is key, however, in starting the in depth look at human cells.



American Chemical Society (ACS). “Bacteria use chat to play the ‘prisoner’s dilemma’ game in deciding their fate.” ScienceDaily, 27 Mar. 2012. Web. 29 Mar. 2012.

Blind as a Bat to Eagle Eye Vision

Approximately 100,000 people in the United States have X-linked retinitis pigmentosa, a form of hereditary retinal blindness.  This form of blindness is passed down from mothers to offspring, but drastic vision impairments are seen mostly in males.  Retinal blindness entails a slow progression of loss of vision. The individual will first lose peripheral and night vision, and then continues to tunnel vision and eventually complete blindness.

Dr. William W. Hauswirth and Dr. Alfred S. Lewin, both professors at the University of Florida, have devised a treatment that may reinstall vision to the individuals who have inherited this unfortunate defect.  These doctors have already had success in the beginning stages of a treatment for a less prevalent vision defect that results in blindness, known as Leber’s congenital amaurosis, but their new treatment presents the opportunity for a bigger impact because hereditary retinal blindness is a much more common vision defect.

Light sensitive cells found in the eye are known as photoreceptors.  These cells are necessary for vision.  X-linked retinitis pigmentosa occurs when these cells are slowly broken down.  This starts in the early stages of life, and as the aging process continues the affected individual slowly begins to lose his or her sight. Complete blindness usually occurs around the second decade of life.   Imagine being a young teenager and literally watching the world disappear around you.  This is what motivated these doctors to try and find a treatment for this type of blindness.

The strategy for this treatment was to create a functioning copy of the affected gene and then turn it into a virus.  The “virus” would then be used as a delivery system to the part of the eye where the malfunctioning form of this gene is located.  An “on-off switch” was also copied and would help turn the “virus” on once it was in place.  This would result in the functioning gene releasing necessary proteins that would activate the otherwise damaged light sensitive cells.

This type of therapy that Dr. Hauswirth, Dr. Lewin, and fellow coworkers from the University of Pennsylvania have derived falls under the heading of “gene therapy”.  The researchers were able to inject these functioning genes into canines that had vision defects that mirror the retinal heritable blindness.  The functioning genes made their way only to the eye where they were needed.  They were not found anywhere else within the body.  The researchers are hopeful that this is how the treatment will also work within humans.

Although this may seem like an instant cure, there are numerous steps and procedures that these Florida and Pennsylvania researchers still need to follow through with in order to create a working treatment.

So what’s the game plan?

The researchers plan on continuing to develop the gene therapy and creating a version of the “virus” that is completely safe to humans. A large scale clinical trial will then have to occur, which will hopefully provide evidence that a treatment for this type of heritable vision defect has been found.



William A. Beltran, Artur V. Cideciyan, Alfred S. Lewin, Simone Iwabe, Hemant Khanna, Alexander Sumaroka, Vince A. Chiodo, Diego S. Fajardo, Alejandro J. Román, Wen-Tao Deng, Malgorzata Swider, Tomas S. Alemán, Sanford L. Boye, Sem Genini, Anand Swaroop, William W. Hauswirth, Samuel G. Jacobson, Gustavo D. Aguirre. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1118847109

University of Florida Health Science Center. “Researchers develop gene therapy that could correct a common form of blindness.” ScienceDaily, 23 Jan. 2012. Web. 6 Mar. 2012.

Could it be? A Drug that Cures Cancer and Alzheimer’s disease?

Amyloid beta (red areas-left image) peptides clear from the brain of an Alzheimer's mouse after three days of treatment with a cancer drug (right image). Souce: AAAS/Science

Neuroscientists at Case Western Reserve University School of Medicine have just reported a breakthrough in their efforts to find a cure for Alzheimer’s disease (AD). The findings, published in the journal of Science, show that the administration of a drug in mice appears to quickly reverse the pathological, cognitive, and memory deficits caused by the onset of AD.

The drug with this potential: Bexarotene. Bexarotene has been FDA approved for the treatment of a type of skin cancer for more than a decade. The Landreth lab at Case Western explored whether this medication would also be useful in treating patients with Alzheimer’s disease. The results the lab obtained were more than promising.

Before I delve into their findings, it is important to understand basic AD pathology. AD arises in large part from the body’s inability to clear naturally-occurring beta amyloid from the brain. In 2008, members of the Landreth lab discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. So, they decided to explore the effectiveness of bexarotene for increasing ApoE expression. This was based off the idea that elevation of ApoE levels speeds the clearance of amyloid beta from the brain and bexarotene acts by stimulating the receptors which control how much ApoE is produced.

The researchers were stunned by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of AD. Today, the scientific community agrees that small soluble forms of amyloid beta cause the memory impairments displayed by animal models and humans with the disease. Within just six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent. Even more astonishing was the fact that the effect lasted three days and was correlated with rapid improvement in a broad range of behaviors in three different mouse models of AD.

Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reductions totaled 75 percent. The research team believes that the bexarotene reprogrammed the brain’s immune system to “eat” the amyloid deposit which demonstrates that the drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and thus, reverses the pathological features of the disease in mice.

This study also identifies a link between the primary genetic risk factor for AD and a potential therapy to address it. Humans have three forms of ApoE: ApoE2, ApoE3, and ApoE4. Carriers of the ApoE4 gene are at an increased risk for developing Alzheimer’s. The Landreth lab has previously shown that the e4 variant was impaired in its ability to clear amyloid. These new results suggest that elevation of ApoE levels may be an effective strategy to clear the forms of amyloid associated with impaired memory and cognition.

The Landreth lab is in the very early stages of beginning the translation to clinical trials of the drug. One can only hope that this drug has some effect on amyloid clearance in humans similar to that seen in the mouse models.

It is important to note that while this study appears to be a dramatic breakthrough in the efforts for finding a cure for AD, the results were only found in mouse models of the disease. There have been 300 reports of treatments that cure Alzheimer’s in mice since 1995. Unfortunately the number of cures in humans in 2012 still reads zero. This is because while the mouse model holds genetic mutations that cause mice to display similar cognitive impairments, it is an imperfect model for a true AD patient. No single mouse replicates all the symptoms associated with human Alzheimer’s disease. The exact cause and progression of AD remains unknown, which makes finding a cure difficult when we still haven’t even unwrapped the actual problem. Lastly, if this drug were to be effective in humans, it still would not help the patients in the advanced stages of Alzheimer’s, whose memory loss and impaired cognitive abilities are the result of neuronal death. Bexarotene can reduce levels of amyloid beta, but unfortunately it cannot reverse cell death.

Point being, while these new results hold promise for the future of AD, we must not forget that there is much more to be discovered about the cause and progression of this terrible disease.

Resource:  Cramer, et al. ApoE-Directed Therapeutics Rapidly Clear Beta-Amyloid and Reverse Deficits in AD Mouse Models. Science (9 February 2012) DOI: 10.1126/science.1217697