Our immune systems to blame for unsuccessful HIV vaccines?

By Johnathan Nieves ’11

Cells known as regulator T cells are being implicated in limiting the effectiveness of therapeutic vaccines for HIV by suppressing the immune system. This new knowledge may help researchers when developing future HIV vaccines.

Our immune system may be a little dumber than we thought. Cells involved in the body’s immune system are being implicated in limiting the effectiveness of therapeutic vaccines for HIV. A recent study published in the journal PLoS ONE on March 24th, demonstrated that regulatory T cells are involved in reducing the effectiveness of HIV vaccines by suppressing the immune system. The findings of the study may help researchers improve the effectiveness future therapeutic HIV vaccines.

Regulatory T cells (Treg) are important because they prevent the body’s immune system from attacking itself. When the immune system attacks itself, it is the result of it mistaking a non-harmful entity, like a liver cell, for a harmful one. The non-harmful entity is then tagged for destruction and the body’s immune system would destroy it and anything similar to it. This is known as an auto-immune response. Without Treg, autoimmune diseases could flourish.

So what if Treg cells are suppressing the immune system so that novel therapeutic HIV vaccines cannot be recognized and targeted for destruction?  University of Pittsburgh health science researchers sought to answer this question as a follow-up to an HIV vaccine they developed and tested in 17 HIV positive patients in 2008 that produced unsatisfying results. In the study the researchers removed Treg cells from the patients’ blood samples to see what effect the HIV vaccine would have on the sample in the absence of Treg. To their surprise they found that Treg reduced the patients’ immune system’s ability to recognize the HIV vaccine and begin to target the actual HIV virus in the patients blood.

“When we removed Treg from blood cells, we found a much stronger immune response to the vaccine, giving us insight into how we can develop more effective HIV vaccines,” said Charles R. Rinaldo, Jr., Ph.D., the study’s lead author. “Treg normally shuts down [the immune response] once the infection has been controlled, but in this case it appears to be [suppressing the immune response] early and possibly limiting the vaccine’s ability to do its job effectively.”

One theory is that the HIV infection itself is responsible for increasing Treg levels in the blood which in turn results in the immune systems inability to recognize the HIV virus.

“We know how to treat HIV, but are still learning how to use immunotherapy strategies to completely flush it out of the body,” added Bernard J.C. Macatangay, M.D., co-author of the study. “Our findings show Treg plays an important role, but we need to figure out how to maintain the right balance by getting around these cells without blocking them completely.”

To view the press release pertaining to this article, click here

The journal article pertaining to this article may be obtained here.

Nano probes: the future of drug delivery?

by Johnathan Nieves ’11 

Scientists have developed an extremely small probing device that is capable of binding to a cells surface and eavesdropping on its internal electrical activity. This may help to provide insight into how cells communicate and how they respond to medication delivered through the probe.    

Ever think we could spy on a cell? We have been able to for almost thirty years now, but a new technique is purported to no do it substantially better. Stanford Researchers recently (March 30) published a paper describing their success in developing a nanometer-scale probe capable of binding and becoming a part of a single cell’s membrane.  The paper, published in Proceedings of the National Academy of Science, offers insight into the ability for researchers to eavesdrop on the inner electrical activity of individual cells. The use of the nano probe as a conduit for inserting medication into a cell’s interior is also being cited by the Stanford researchers.    

The study, spearheaded by Nick Melosh and Benjamin Almquist, focused on designing a probe in a way that allowed it to mimic a component of the cell membrane. The cell membrane, or cell wall, is the outermost encapsulating structure of a cell that protects it from the outside environment. The key to the probe’s easy insertion and the great affinity it has for the cell membrane is due to its engineering. The probe was engineered in a way that allowed it to mimic a type of cell membrane gatekeeper protein – a molecule naturally found in the cell membrane that regulates what enters and exits the cell.      

Image depicting the nano-probe binding to the cell membrane. (Credit: Benjamin Almquist, Stanford University)

“What we have done is make an inorganic version of one of those membrane proteins, which sits  in the membrane without disrupting it,” said Melosh. “The probes fuse into the membranes spontaneously and form good, strong junctions there.” The attachment is so strong, “we cannot pull them out. The membrane will just keep deforming rather than let go of the probes.” The 600-nanometer-long probe has integrated so well into membranes that the researchers have dubbed it the “stealth” probe.    

Current methods involved in cell probing are limited in that they only allow access to the cell for few hours. Additionally, the methods are extremely destructive and damaging to cells. Melosh and Almquist are the first to implant a cell probe with very little damage to the cell.      

Up to now, poking a hole in a cell membrane has largely relied on brute force, Melosh said. “We can basically rip holes in the cells using suction, we can use high voltage to puncture holes in their membranes, both of which are fairly destructive […]; many of the cells don’t survive.” That limits the duration of any observations, particularly electrical measurements of cell function.    

“Ideally, what you’d like to be able to do is have an access port through the cell membrane that you can put things in or take things out, measure electrical currents … basically full control,” commented Melosh. “That’s really what we’ve shown – this is a platform upon which you can start building those kinds of devices.”    

Melosh and Almquist are currently working with human red blood cells, cervical and ovary cancer cells to demonstrate the functionality of the probes in living cells.    

To view the press release pertaining to this article, click here.

The Gift of Sight: Treating Blindness with Gene Therapy

By Johnathan Nieves

Findings from a new study show that gene therapy may be effective in treating a rare disease that progresses to total blindness by adulthood.

 

Imagine how difficult daily activities would be without being able to see. For 1.3 million Americans today, that is the reality they face.  For a subset of individuals, though, gene therapy may be the answer to curing their debilitating disease. Findings from a study published March 3rd in Science Translational Medicine showed that gene therapy may be effective in treating Leber’s congenital amaurosis (LCA), a rare genetic disease that progresses to total blindness by adulthood.

Gene therapy for LCA, which produced dramatic improvements last year in 12 children and young adults who received the treatment in a clinical trial, has cleared another hurdle.  In the human trial for LCA reported last year, researchers at PENN Medicine and The Children’s Hospital of Philadelphia treated only one eye in each of their 12 patients. Because the treatment was experimental, researchers left one eye untreated in the event of unexpected complications. After the patients experienced partially restored eyesight in their treated eyes, many were eager to receive the same treatment in the other eye.

The same research team that conducted the human trial now reports that a study in animals has shown that a second injection of genes into the opposite, previously untreated eye is safe and effective. The study suggests that patients with LCA who benefited from gene therapy in one eye may experience similar benefits from treatment in the other eye.

“We designed this study to investigate the immunological consequences of administering the

Source: U.S. National Library of Medicine

gene therapy injection to the second eye after treating the first one,” said corresponding author Jean Bennett, M.D., Ph.D., F.M. Kirby professor of Ophthalmology at the University of Pennsylvania School of Medicine. “The good news is that in animals, the second injection, like the first, is benign.”

 As in the human trials of this gene therapy, the researchers packaged a normal version of the missing gene that causes LCA into a vector. The vector, a viral messenger that is used to incorporate a gene into a cell’s DNA, was used to deliver the gene therapy to cells of the retina, the light sensing region of the eye. Once in the retina cells, the vector is able to incorporate the gene into the cell’s DNA. Once incorporated into the DNA, the cell’s DNA reading machinery can translate the gene and produce an enzyme that restores retinal function, effectively reversing blindness (to view an animation of this processess click on the image above).

 Although the virus used in the study does not cause human disease, it previously set off an immune response that cut short the initial benefits of gene therapy. In the current study, the team found no evidence of toxic side effects in the 10 animals that received treatment. All the animals, which had been specially bred to have inherited blindness, had improved vision, and showed no toxic effects from the treatment.

The study “provides encouraging indications that immune responses will not interfere with human gene therapy in both eyes,” said co-author Katherine A. High, M.D.  Additionally, the results may set the stage for gene therapy in LCA patients who were excluded from the previous trial. At present, the research team is planning another clinical trial of LCA gene therapy, which may include some of the patients from the first human trial.

 To view the original press release pertaining to this article, click here.

Drugs That Kill Bacteria Can Also Make Them Stronger

By Johnathan Nieves ‘11

A recent study showed that exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug under development by Radnor, PA-based PolyMedix, Inc. shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.

Click on the Image above to see Polymedix's Drug In Action (Sources: Image, World Health Organization; Video, Polymedix, Inc. )

If you don’t take your prescription antibiotics as your doctor advises, then listen up. Just last week (February 12) a paper published in the journal Molecular Cell described how exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug currently under development by Radnor, PA-based PolyMedix, Inc., however, shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.

Drug resistance has been a growing health concern for decades now since the introduction of penicillin in the 1940s, the first available antibiotic of its kind. Drug resistance occurs because of bacteria’s natural ability to evolve through mutations it incurs as it reproduces. As it turns out, researchers have found that low antibiotic dosages are triggers for increasing the rate at which bacteria mutate, thus, increasing the likelihood of drug resistance.

“Like anything in nature, bacteria have ways to fight its opponents, and do so either by pumping antibiotics out of themselves through a process called efflux, or by rapidly mutating and changing the shape of the target of attack of the antibiotic drug. They can do this, even with large doses of antibiotics, it’s their innate way to try to survive,” explains Bozena Korczak, Vice President of Drug Development at PolyMedix Inc..”

“Upping the antibiotic dosage may be a viable solution but not the ultimate one,” adds Korczak. Driven by science conducted at the University of Pennsylvania, PolyMedix is investigating a new type of antibiotic drug that works by imitating the human immune system.

PolyMedix’s investigational antibiotic agent, called PMX-30063, is the first of its kind with a new approach to address the serious health implications of drug resistance by mimicking host defense protiens. Unlike most antibiotics, host defense proteins work fundamentally different. Rather than crossing the bacterial membrane to find a target like most antibiotics, they selectively target the cell membranes integrity by poking holes into it. This diminishes the bacteria’s ability to remain intact and the bacteria and its internal components become degraded (See video demonstration by clicking on the image above).

Polymedix purports that this unique mechanism of action makes drug resistance unlikely to develop. Korczak insists that “the best approach to preventing this phenomenon is by directly attacking the bacteria’s cell membrane, rendering them destroyed and dead in a way that there is little chance of resistance.”

To study the ability of bacteria to resist an antibiotic drug, a laboratory experimental method known as “serial passage” is used by intentionally trying to create bacterial drug resistance. Using this experiment, PolyMedix has shown that resistance did not appear to its compounds in contrast to traditional antibiotics.

So far, data from two Phase I clinical studies demonstrate that the compound is safe and well-tolerated. PolyMedix is on schedule to complete the third and final segment of the ongoing Phase 1 study with PMX-30063 early this year and commence Phase 2 studies later this year.

PolyMedix has received 9 grants and research contracts from the National Institutes of Health and branches of the military to help support the development of its antibiotic compounds.

To view the press release associated with this piece, please click here.

To learn more about PolyMedix, Inc., please visit www.polymedix.com.

New Drug Shown to Heal Back Pain in 3 Days

By Johnathan Nieves

Source: Belmar-Fitness

Lower back pain is the fifth leading cause for doctor visits in the U.S. and over 85 percent of people suffer at least one bout of lower back pain in their lifetime. SOMA®, a new drug under development by, Meda Pharmaceuticals, Inc., a Somerset, N.J. based company, has been shown to improve functionality and reduce disability associated with lower back pain in as few as three days as confirmed by patient outcomes data.

The “outcomes data differentiates SOMA® 250 mg among the diverse treatment choices for patients with acute low back pain,” said Steven M. Simon, MD, RPh, Clinical Assistant Professor at the University of Kansas School of Medicine and Biosciences.

“Almost all acute low back pain is mechanical in origin and one in five patients with this condition suffers from significant limitations in activity.  Treatment of acute low back pain with SOMA® 250 mg has been shown to improve functionality, as measured by an internationally validated tool.”

Meda Pharmaceuticals, Inc. claims that SOMA® is the only skeletal muscle relaxant proven to significantly improve functionality in patients with acute low back pain as measured by the Roland-Morris Disability Questionnaire (RMDQ), an internationally validated standard for measuring the degree of disability and functionality in patients with lower back pain.

The Company’s approach to assessing patient symptom progression during SOMA® treatment via the RMDQ is unique in that it is a form of outcomes-based healthcare. Outcomes-based health care has become an increasingly popular and comprehensive approach to healthcare with goals of providing high quality care and reducing treatment costs.

“Overall, the greatest cost savings from a societal perspective may be obtained from interventions that promote early return to work and minimize lost productivity,” said Al Moorad, MD, Medical Director, Integris Jim Thorpe Rehabilitation, Oklahoma City. “This may be accomplished by appropriate drug utilization to allow patients to actively participate in rehabilitation therapy and return to daily activities.”

Meda Pharmaceuticals’ will present its findings this week at the 26th annual meeting of the American Academy of Pain Medicine in San Antonio, TX.

To learn more about SOMA®, you may visit www.SOMA250.com. The original press release pertaining to this article may be viewed at www.prnewswire.com.

Johnathan L. Nieves

Johnathan Nieves is a Biochemistry and Molecular Biology degree candidate at Dickinson College where he is also pursuing a Certificate in Health Studies. Mr. Nieves currently works freelance for The Investor Relations Group, Inc. a full-service corporate communications firm based in New York, New York and hopes to pursue a career in medicine after graduation.