Compound reduces amyloid plaque, symptoms of Alzheimer’s disease in mice.
Alzheimer’s disease (AD) has been linked to the buildup of amyloid plaque in the brain. A recent study indicates that an RNA-like compound that decreases the production of amyloid beta protein may reverse symptoms of AD such as learning and memory loss.
Researchers at Saint Louis University explored the effects of their potential drug, antisense oligonucleotide (OL-1), in a mouse model of AD. The mice were genetically engineered to overexpresses a mutant form of the human amyloid beta precursor gene, causing amyloid plaque to build up in their brains to produce the symptoms of AD. The antisense oligonucleotide (OL-1) is a chain of nucleic acids designed to bind to amyloid beta precursor messenger RNA, preventing its translation into the plaque-forming protein.
The scientists found that, after treating the mice with OL-1 three times over six weeks, the memory and learning of the genetically engineered mice rose to levels equivalent to those of wild mice given a placebo. They were also able to demonstrate that OL-1 was able to penetrate into the brain after administration through the mice’s tail veins.
The researchers hope to develop OL-1 into a treatment for AD. Their next steps are to test the molecule for any toxic effects and, if it is safe, study its effect in humans.
Researchers at the University of Missouri have published a study exploring the 3D structure of a molecule related to soy sauce flavor enhancers that has potential as a treatment for HIV.
The molecule, called EFdA, was created by a Japanese soy sauce company while they were experimenting with new compounds to enhance the flavor of their sauce. The main reason scientists are interested in EFdA is that it has been shown to be effective against viral strains of HIV that have become resistant to currently approved treatments.
EFdA turned out to fall into a class of compounds called nucleoside analogue reverse transcriptase inhibitors (NRTIs). These chemicals inhibit the replication of HIV, and eight compounds similar to EFdA are already in medical use.
This study uses nuclear magnetic resonance spectroscopy (NMR) to elucidate the 3D conformation of EFdA, hoping to pin down exactly how the molecule physically interacts with its target, reverse transcriptase. This information could help chemists design new drugs that optimize these interactions, increasing the drugs’ potency while decreasing viral
Patent Mythology #3
The Myth: What doesn’t work isn’t important.
The Reality: To be patentable, an invention must be new, useful and non-obvious. When your patent attorney is preparing your patent application, providing her with a good written record of what doesn’t work can be very helpful. Why? Because what didn’t work can be added to your application. During patent prosecution, your attorney may have to provide arguments to overcome a rejection from the examiner that your invention is not patentable because it is obvious. If you had 50 failures before your first success, you have strong evidence of non-obviousness.
So keep good, detailed records of your work. Have the records dated, signed by the inventor and witnessed by someone who read and understood the work. Keeping a record of your failures and successes may make all the difference in overcoming the examiner’s rejections and getting your patent claims allowed.
Patent Mythology #1
The Myth: Patents aren’t valuable. You can just make small changes and get around them.
The Reality: Many patents are extremely valuable. Monsanto was given a one billion dollar award ($1,000,000,000) in its law suit for patent infringement against DuPont/Pioneer. Clearly not every patent is going to be that valuable. The value is determined by how much is already in the public domain and consequently can’t be claimed in your patent, how well the application was drafted by the attorney, and how great the invention is.
Choosing a skilled patent attorney is critical in getting a valuable patent. Clearly, not every intellectual property lawyer is the same. St. Louis’ thriving entrepreneurial community is a great place to network and learn from successful business people the names of the best intellectual property attorney for your invention.
Patent Mythology #2
The Myth: A great idea is an invention.
The Reality: A great idea is…..an idea. An invention is the tool, technique, composition, method or device that makes that idea a reality. My six year old son told me, “Mom, I have an invention!” “Great!” I replied, “What is it?” “A car that gets 100 miles per gallon.” I told him, “That’s an idea, not an invention. When you build that car, I’ll patent it for you.”
A great idea is a great start. Now get to work. First do some searching to see if your idea is new. We recommend Google Scholar, because it has a very helpful format for searching patents. It’s important to know that you not only must have a new idea, it must be non-obvious. Several patents can be combined to make an idea obvious. Once you have determined that your idea is new and non-obvious, you need to work on a prototype. It doesn’t have to be the best embodiment, it just needs to demonstrate the concept. I’ve been impressed with what can be demonstrated with cardboard and duct tape. The new 3-D printers are making prototyping easier than ever. Then, when you’ve made that idea a reality, contact your patent attorney.
Gender difference in MS linked to protein expression.
Researchers have observed that women are four times more likely to be diagnosed with multiple sclerosis (MS) but, until recently, have had no clues to explain the gender difference. This summer, scientists at Washington University School of Medicine put forward a study that links MS and gender to a protein expressed in brain blood vessels.
The protein, called S1PR2, helps to regulate the blood-brain barrier, which protects the brain from harmful substances while allowing in nutrients in healthy individuals. While some proteins help keep the barrier closed, S1PR2 works to keep it open. The researchers found that this protein was more active in female mice used as models for MS than the males.
Higher levels of S1PR2 may be detrimental in individuals affected by MS, which is an autoimmune disorder. In MS, immune cells become misdirected and attack the nerve cells in the brain a spinal column. Higher levels of S1PR2 may allow these inflammatory cells easier access to the brain.
The scientists followed up this study by examining brain tissue samples from 20 human patients after death. The MS patients had more S1PR2 in their brains than patients without the disorder, and that the female patients also had more of the protein than the males did.
Researchers hope to design a drug that inhibits S1PR2 to treat MS, and the authors of this paper are working on a method to monitor S1PR2 levels in the brains of living patients.
The study was published in the Journal of Clinical Investigation, an open access journal, and is available to the public here.
Strains of misfolded tau proteins linked to neurodegenerative diseases
A recent study from Washington University School of Medicine suggests that different neurological disorders, including Alzheimer’s disease, may be associated with distinct prion-like versions of the protein tau.
The study’s authors had previously shown that tau can misfold into several different structures, or “strains.” The strains acted like prions, infecting cells and causing the cells’ proteins to misfold, sometimes generating a cascade effect leading to disease.
Clumps of misfolded tau proteins have been identified in 25 different neurodegenerative disorders, known as “tauopathies.” The scientists wanted to know if different strains of tau were associated with specific tauopathies. The researchers were able to study misfolded tau in five of these neurological disorders, including Alzheimer’s diseases, using brain samples from 28 neurological patients after they died.
They found that each tauopathy had a unique tau prion strain or combination of strains associated with it. For example, the same tau prion strain was observed in nearly every brain affected by Alzheimer’s disease.
The researchers were also able to show that the tau strains were stable by using them to infect mouse brains, and then using the misfolded proteins produced in these brains to infect other mouse brains. The different tau strains were also observed to induce different kinds of brain damage in the mice.
The researchers are working to find a non-invasive way to sample tau strains from patients for diagnostic purposes. They have also suggested that monoclonal antibodies might be developed to target the different tau strains as a treatment for their associated neurological diseases.