Gene Therapy Helps Patients With Hemophilia

“During coagulation, erythrocytes become trapped in a
fibrous mesh with the help of clotting factor IX”

A recent study from the University College London and St. Jude Children’s Research Hospital reported that gene therapy cells might protect hemophilia B patients from bleeding extensively. This is truly a “landmark case” because Hemophilia is a rare inherited disorder where the blood does not undergo the coagulation process appropriately. “As a result, patients experience bleeding after injury. This type of hemorrhage can potentially damage organs and tissues”. The treatment for this disorder is called replacement therapy and this procedure must be repeated regularly “which carries risks”. The alternative method was gene therapy where the scientists conducted this study on “four patients who went through medium doses of therapy have generated enough clotting factor IX themselves that they ceased to get preventive infusions”. The “driving force” for this therapy is the virus called “AAV-8” that targeted liver cells which naturally produce clotting factor IX. Moreover, this virus does not interfere with the DNA or the cells’ normal function. So, this makes it an ideal source for the therapy. Only liver inflammation was seen in these patients, but no other side effects emerged.
Although there were previous studies that enable the scientists to think that gene therapy could be promising for correcting disorders such as hemophilia, they, in fact, produced disappointing results. According to NHLBI Director Dr. Susan, results from this study might provide “a promising step to further findings”.


http://www.nih.gov/researchmatters/december2011/12192011hemophilia.htm

Erythrocyte Ghosts for Gene Therapy

One of the main challenges faced by researchers working on drug delivery and gene therapy is how to effectively target the therapy to the area that needs it and to ensure that the drug stays in the body for an extended period of time. Various methods have been tried, from straight injection of DNA to cationic vectors to improve the survival time of the DNA in the blood. However, these methods are less than ideal when it comes to gene therapy. For example, the vector approach uses nonviral vectors, which are actually toxic to the body. To various teams of researchers, it seems that a simple answer to this problem has presented itself in the form of erythrocytes, or red blood cells.

Erythrocytes are biocompatible, relatively long lived, are found in abundance in the body, and travel all over the body. In this article, a team of researchers was able to manipulate the erythrocyte membrane in order to encapsulate plasmid DNA within the cells. These loaded cells, or “erythrocyte ghosts”, were then tested in circulation in mice and the life of the DNA was compared to the life of DNA in other methods of delivery. Researchers observed that the plasmid DNA-loaded erythrocyte ghosts survived and remained active in vivo much longer than that of plain injected plasmid DNA. They also reinforced the idea that targeting can be achieved through the blood stream and proved the viability of erythrocyte ghosts as carrier agents for therapeutic drugs in the body.

This article intrigued me because of its minimally invasive approach to solving a problem. Using erythrocyte ghosts works in sync with the body’s natural systems to fix the problem in lieu of harsher methods that could cause more damage to the body. It seems to me that a smart move in medicine is to make use of the body’s own capabilities in medical treatments, which is precisely what the erythrocyte ghost method does. The use of erythrocyte ghosts could have a far reaching impact past just gene therapy. In fact, there is research being conducted in our own biomedical engineering department for other uses of erythrocyte ghosts (see link at bottom). The potential for erythrocyte ghosts is immense and is definitely a unique approach to solving problems in the body.

http://www.nature.com/gt/journal/v11/n5/full/3302180a.html

http://www.nature.com/nrd/journal/v2/n9/full/nrd1189.html

http://biomed.tamu.edu/meissnerlab/Research.html

Gene Therapy Cures Malignant Melanoma in Mice

A new method of cancer treatment has been tested in mice that uses gene therapy to trick the body's immune system into destroying the tumor (and any cells that have metasasized). The trick was in identifying a specific protein receptor only present in melanoma cells. A gene coding for a complimentary protein (a protein that binds to the melanoma protein) was introduced into hematopoietic stem cells in the bone marrow of the mice. These cells differentiate into T cells which contain the anti-melanoma gene and will destroy any melanoma cells that they come into contact with. One of the interesting features of this type of treatment is that these stem cells will continue to produce T cells with these receptors for the lifetime of the patient, eliminating the potential of future tumors. Also, this treatment could be used to preempt cancer, like a vaccine, by introducing the gene before any tumors develop, preventing them.

This potential treatment is very exciting. If treatments like this could be designed for other types of cancer, cancer could be effectively cured, even in the most severe cases where the cells have traveled around the body. The body's immune system in far more precise than any surgeons blade.

http://www.sciencedaily.com/releases/2010/11/101118124206.htm

Non-viral Gene Delivery with Stents for the Treatment of Restenosis

Scientists and engineers at Northeastern University and the University of Pittsburgh collaboratively designed and performed an animal trial to demonstrate how gene eluting stents can be made to alter the gene expression of the tissues they contact in order to treat or prevent restenosis of the artery. In this study, the researchers used liposome structures, adhered to the stent in a gelatine mixture, to deliver a gene coding for human endothelial nirtic oxide synthase to the tissue around the stent. Nitric oxide is useful in the treatment and prevention of restenosis because it both discourages smooth muscle growth, which is a cause of arteriosclerosis, and promotes healthy endothelial growth to cover the damaged areas of the artery. A gene that produces this enzyme that catalyses the production of nitric oxide provides an opportunity to help the body essentially heal itself. Another notable accomplishment of the study is that they were able to introduce the genes without the need for a virus vector, which can have a high cytotoxicity and is unlikely to be used in a clinical setting.

This study could have a huge impact upon future treatment of cardiovascular disease. Today, stenting is done routinely, and restenosis is a very common problem, sometimes requiring additional surgery and other therapies. As this problem has become obvious, drug eluting stents have become the weapon of choice against restenosis. Drug eluting stents, however, are imprecise (their drugs affect more than the immediate area), and the drugs they carry could be improved upon. Using a form of gene therapy to temporarily induce the cells in the damaged area to produce nitric oxide would be a very attractive therapy either alone or in tandem with other therapies to treat restenosis, especially if it could be done without a virus vector.

This article is highly interesting because of its implications in the treatment of one of the most common causes of death in the developed world: cardio vascular disease. It is interesting how the researchers were able to think a little bit outside the box in treating this common disease.

http://www.biomedical-engineering-online.com/content/9/1/56

Treating Color-Blindness in Adults

Color-blindness is defined as a person's inability to perceive differences between certain colors that others can distinguish. The causes of colorblindness are usually either genetic or brought on by neurological damage. Colorblindness tends to affect males more than females if genetic, and the most common types are red-green photoreceptor disorders, though there are a great variety of other types. Though color-blindness doesn't seem like a very serious disability, in some countries, it is not possible to get a driver's license without normal vision, and a color-blind person will have a hard time dealing with anything that is color-coded.

Currently, there is no way to "cure" color-blindness. Doctors will sometimes prescribe tinted lenses to help with the problem, but these are not completely practical treatments because they have their drawbacks. However, there is one branch of research that might provide another way to treat this disorder: gene therapy.

Up until now, no one considered gene therapy to be a useful treatment because color-blindness isn't usually diagnosed until later in a person's life. Doctors and researchers were convinced that these people were too old to respond to gene therapy treatment properly.

However, a recent study on adult monkeys shows that might not be the case. Monkeys that were color-blind since birth were effectively treated by gene therapy, even though they had already reached adulthood. This suggested that adult human brains might be able to respond to this treatment as well.

For now, there is no human gene therapy for color-blindness, but these animal tests prove promising. Scientists had never really considered an adult human brain to be able to respond to this type of gene therapy, but there is proof now that at least monkey adult brains can re-wire themselves in response to such treatments. One day, this might help not only treat color-blindness in humans, but other, more life-threatening diseases.

Sandhya Ramesh
VTPP 434 501

http://www.lifescientist.com.au/article/318765/gene_therapy_cures_colour_blindness?fp=4&fpid=3