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.

New brain-imaging technique can predict who will suffer from Alzheimer’s and accelerate research


These are baseline and follow-up brain scans of a patient who converted to Alzheimer's disease after two years (images to right of white line) that shows high medial temporal binding at baseline (lower left) and follow-up (lower right), but also demonstrates more baseline binding in frontal (upper images) and lateral temporal regions. Warmer colors (yellows, reds indicate higher binding levels. A second patient did not convert to Alzheimer's after two years (images to left of white line) showing medial temporal (lower scans), but very mild frontal (upper scans) binding at baseline and follow-up. (Credit: UCLA)

Brain degeneration associated with the loss of memory and other cognitive functions currently affects millions of adults, and this number will only increase as the baby boomer generation continues to age. Today, almost 20 percent of the population that is 65 or older suffers from mild cognitive impairment (MCI) and 10 percent have diagnosable dementia.

Researchers from UCLA report in the February issue of the journal Archives of Neurology that the brain-imaging technique they had previously reported as being a possible assessment tool for measuring neurological changes associated with dementia and Alzheimer’s disease has produced promising results.

The UCLA team created a chemical marker called FDDNP that binds to both plaque and tangle deposits – hallmarks of Alzheimer’s disease (AD) – which can then be viewed using a positron emission tomography (PET) brain scan. This technique essentially provides researchers with a “window into the brain” allowing them to pinpoint where in the brain these abnormal structures are developing.

Further, they are “finding that this may be a useful neuro-imaging marker that can detect changes early, before symptoms appear, and it may be helpful in tracking changes in the brain over time,” said Dr. Gary Small, a member of this UCLA lab team.

The study, reported in February, assessed 43 participants who, at the start of the 2-year study, did not have dementia. Participants had an average age of 64 years and about half of the participants (22) had normal aging and the other half (21) had mild cognitive impairment (MCI), a condition that increases a person’s risk of developing AD. The results showed that for both groups, FDDNP binding had increased in the brain and that this was associated with progression of cognitive decline.

For the patients with MCI at the start of the study, the level of initial binding provided the greatest accuracy in identifying those who developed AD after two years. Specifically, six of the 21 participants in the MCI group were diagnosed with AD at the 2-year follow-up. Similarly, for patients in the normal aging group, three of the 22 participants developed MCI at the follow-up and two of these three participants had the highest initial baseline FDDNP values.

The next steps for this research are examining changes over a longer period of time with a larger sample and also using this labeling/imaging technique to track the effectiveness of clinical interventions for brain aging. More specifically, the UCLA lab team will be tracking the effectiveness of a high potency form of curcumin – a recently FDA approved spice with anti-amyloid, anti-tau and anti-inflammatory properties – that can prevent the accumulation of the plaques and tangles that are hallmarks of AD.

The discovery of new imaging techniques that allow scientists to monitor changes in the AD brain is extremely exciting. Prior to these techniques, researchers were only able to examine the pathology of AD in post-mortem brains. These imaging techniques allow researchers to monitor the development of AD in real-time and can prove to be very useful in accelerating drug discovery efforts.


G. W. Small, P. Siddarth, V. Kepe, L. M. Ercoli, A. C. Burggren, S. Y. Bookheimer, K. J. Miller, J. Kim, H. Lavretsky, S.- C. Huang, J. R. Barrio. Prediction of Cognitive Decline by Positron Emission Tomography of Brain Amyloid and Tau. Archives of Neurology, 2012; 69 (2): 215. Link to article
University of California, Los Angeles (UCLA), Health Sciences (2012, February 13). Brain-imaging technique predicts who will suffer cognitive decline over time. ScienceDaily. Retrieved March 1, 2012, from


Budget Likely to be Pulled for Stem Cell Research in California

Learning to do more with less: California Institute for Regenerative Medicine must face the future of its success without state funded support

It seems despite the famous words “mo money, mo problems” from the well-known (and loved) 1997 hip-hop song by Biggie Smalls, the California Institute for Regenerative Medicine in San Francisco is dealing with the opposite situation. They have less money than ever before, and experiencing many, many more problems.

Half of the 3 billion dollars given to the institution from the state of California has been spent, and the other half is expected to dry up by as early as 2021.  It doesn’t look like CIRM will be getting any more money from California either. Jonathan Thomas, the chairman for CIRM has been quoted to say that the institute would be “premature to even consider” receiving any funding from the state in the future.  This, of course, is ominous news for scientists and researchers hoping to make significant breakthroughs in stem cell research during the upcoming years. At the end of the day, no money, mean means no research.  And no research could mean big problems.

With the general economy of the many states in the US in an unfortunate condition, budget cuts must be made. California is no different.  Many residents of the state feel that with several pressing matters to deal with, spending a few billion dollars to support stem cell research is not at the top of their priority list.

In spite of what the public may think, scientists at CIRM have not been sitting idly in the eight years since it was founded.  They have been busy constructing new bindings and labs, training staff, and staring numerous research projects.  Despite all of their efforts, it would be near impossible for the scientists at CIRM to give a single solid example of a fully proven research answer that has arisen in the last eight years.  Much of their findings are preliminary and many others aren’t ready for human trials yet.

It is important to keep in perspective that breaking new ground in the scientific field takes time as well as patience, and that “pulling the plug” so to speak, on stem cell research will do more than retard the progress in that field in the United States- it will essentially stop it completely.  Many other scientific institutes including the National Institutes of Health (NIH) and the Howard Hughes Medical Institute do not support embryonic stem cell research.  Therefore, if the state chooses to no longer fund stem cell research at CIRM, it is highly unlikely they will find funding anywhere other than private sources.

All scientists ask of the public is for patience and a bit of funding.  What could have become of world travel if the Wright brothers gave up on their airplane models halfway through their trials? Where would we be now if Thomas Edison had thrown in the towel after a few failed attempts at the light bulb seemed to be too expensive a task to keep working on? If Watson and Crick weren’t as patient as they were during their time making the first DNA model, would the modern age of genetics have occurred at all?

So many technological advances in science today that we take for granted are a direct result of long years of effort on the part of the scientists working on the experiments.  The most we can do as members of the public is to provide the funding necessary to upkeep the scientists and their experiments, and give a little patience to allow them to get the work done.   Do these two things, and I am quite sure we will have an amazing breakthrough waiting for us in the line of stem cell research.

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 

Giant leap forward for stem cell research

Whether you like it or not, scientific advancement with stem cell research is happening every day around the globe. One of the world’s top rated scientific journals, Science, published an article in September 2006 about a European team of biologists have established a line of pluripotent stem cells, cells that can develop into any and all cell types, that did not involve the demolition of human embryonic cells.

Many scientists hope that this new discovery will quell many people’s objections to such research.  What is unique about this particular study, headed by Miodrag Stojkovic, is that the research team waited at 24 to 48 hours after the last cell division before using the embryo cells for their research study.  This should hopefully diffuse a lot of the negativity some people may feel towards stem cell research, and the idea that it harms potential human life.  By waiting at least 24 hours after the last embryonic division, the scientists ensured that the cells were no longer viable, and thus feel like there was no harm in using those arrested cells for study.

The stem cells that have "arrested" their growth can be used by scientist for therapeutic research.

After collecting the no longer viable cells the team of biologist separated the zona pellucida, the outer covering of the cell, from the rest of the cell, and placed the cell into a plate to grow and replicate.  Of the 13 cultures, only five of the cells were successful when placed into live mice.

Stojkovic’s team claims that about two thirds of all embryos used for in vitro fertilization arrest their development before they reach the stage for implantation in the womb.  Scientists will now, hopefully, be able to use these arrested cells that were previously discarded.  This new method of research could allow scientists to explore “hopeful possibilities,” says William Hurlbut of Stanford University, who was not involved in this study.  Hurlbut hopes, like many others, including myself, that Stojkovic’s method of attaining human stem cells will lead to increased funding from outside sources whom previously refused to offer aid to research teams whom, in their eyes, harmed potential human life.  Unfortunately, even with this new advancement in stem cell research, there is still some debate amongst scientists as to the exact criteria for embryo death.

If successful, stem cell research can lead to leaps and bounds forward in therapies and medicine.  Successful stem cell therapies could be used to allow a patient’s body to heal itself with its very own cells.

So what does this mean for the future of stem cell research? How could this one-day affect the every day citizen of the United States? Of the world? Is type of research what you had in mind before you know what stem cell research was?  Where do you believe stem cell research should go from here?