Gene Therapy Unlocks Some Mysteries of Depression

The field of gene therapy can count another success, albeit a rather small one. Researchers at Weill Cornell Medical College were able to treat depressive behavior in a mouse model of depression using gene therapy techniques. The research also marks an advance in our understanding of the neurobiology of depression.

Dr. Kaplitt and colleagues created a mouse that expresses lower levels of a specific protein known as p11. The p11 protein promotes the activity serotonergic neurons in the brain, a longstanding target of depression treatment drugs such as SSRIs (selective serotonin reuptake inhibitors. This knockdown mouse displayed signs of depression when subjected to specific behavioral tests.

The way that they created the knockdown mouse was the interesting part. Researchers used an adeno-associated virus to “infect” or introduce a small-interfering RNA (siRNA) into a specific region of the brain called the nucleus accumbens. As a result, cells within this discrete brain region produced less of the p11 protein.

By using gene therapy to introduce this particular siRNA, the scientists were able to influence the behavior of the animal. Treated mice performed poorly on the forced swim test and the tail suspension test, which is consistent with depressive symptomatology. Curiously, when these siRNA treated mice were given antidepressant medications, their performance did not improve. Previous research showed that “depressed” mice (those that were stressed or postpartum) performing poorly of behavior tests would perform better if treated with an antidepressant. These results suggest that variations in human p11 may explain why some people do not experience a benefit from antidepressants.

The implications for human treatment are rather profound. The p11 protein appears to represent a newmolecular target for the development of depression treatments. Current treatment is focused on interfering with serotonin and norepinephrine reuptake. With a new target, pharmaceuticals or gene therapies could be developed to augment p11 expression.

Indeed, that is the immediate direction of future work. Studies are underway in non-human primates to use the adeno-associated virus to upregulate the levels of p11. The idea being that too little p11 not only underlies depression but also makes patients refractory to treatment. As with other avenues of gene therapy research, though, the road is long. A significant amount of efficacy and safety studies need to be performed before we see a gene therapy treatment of this nature in the clinic.

PACE MAKER

As we call it by the name pace maker let us just why it is defined so … defining it… A pacemaker is a small electrical device that runs on a battery and produces low voltage rhythmic electrical signals that keep the heart beating when the heart's own electrical signals are deficient basically in a more simple way A pacemaker continuously "watches" the electrical system of heart and provides the needed electrical signal if the heart does not do so. During periods when the heart produces its own electrical signal normally, the pacemaker does nothing except to continue to monitor. So as it has to be placed within the body it has to be biocompatible, let me come to its biocompatibility a bit later before that lets see the basic part of the pacemaker .

A pacemaker system is made up of three main parts:

• · The generator, a smooth, lightweight case containing a tiny computer and a battery which makes the electrical signals needed to pace the heart;
• · The connector or header, which is the part of the generator where the leads are attached
• · The leads, which are wires covered in soft, flexible plastic that are inserted into the heart to help the generator watch the heart and carry the generator’s signals to the heart.

A A pacemaker may have one or two leads. A pacemaker with one lead is called a single-chamber pacemaker. Where this one lead sits depends on where the signal problem in your heart is. A pacemaker with two leads is called a dual-chamber pacemaker. One lead usually sits in your right atrium, and the other usually sits in your right ventricle. Which type of pacemaker you need depends upon the kind of rhythm disturbance you have and your overall heart function. Depending on your situation, pacemaker will be used

Implanting the pacemaker

Toto implant the pacemaker there is a simple surgical procedure performed in the operating room or in the cardiac catheterization lab. When the decision to implant a pacemaker is made some prior instruction need to be followed

• · Do not have anything to eat or drink for 6 hours before your procedure.
• · If you are a diabetic you may be instructed to reduce or not take your insulin or other diabetic medicine on the day of the procedure to avoid low blood sugar.
• You may be asked stop taking aspirin or other blood thinners several days prior to the procedure to avoid unnecessary bleeding

· Blood tests may be required on the day of the procedure or before it.

· Usually you will be asked to arrive in the hospital on the morning of the procedure several hours before the procedure so that you can be adequately prepared to undergo the surgery. After the procedure usual hospital stay is one day.

During the procedure

Immediately before your procedure, the skin area just beneath the shoulder and above the breast will be cleansed with special soap and may be shaved to remove excess hair. A mild sedative may be given to you to help you relax. The procedure may take 1 to 2 hours to complete. It is usually done under local anesthesia, which means that the area where the pacemaker will be inserted will be numbed with an injection. Subject should not feel any pain during the procedure, and should inform the doctor or staff if you are having pain so that more medication may be given. The most common insertion method is called endocardial (inside the heart) implantation. An incision is made in the skin under the collarbone and a "pocket" is formed under the skin and in front of the muscle in the upper chest for the pacemaker generator to rest in. The lead or leads are then threaded through a major vein in your upper chest and into your heart with the help of x-ray monitors. Their position inside your heart is determined by electrical measurements. Once the leads are in place, they are hooked to the generator, which is then inserted into the pocket that has been made. The pacemaker’s settings are programmed, the incision is closed, and a polybane sterile dressing is placed over the incision.. well some of us are not aware of sterile dressing …its composition is POLYMYXIN B SULPHATE U.S.P. 5000 UNITS and NEOMYCIN SULPHAT U.S.P. 3400 UNITS. It is sterilized by Gamma irradiation . A sterile dressing is a form of absorbent cotton fabric that is generally bonded on both sides so that it does not stick to the wound or area. It is used as wound care to promote the healing of an injury and to prevent more harm to the area. A sterile dressing is different from a bandage, in that a bandage is designed to hold a dressing in place while the sterile dressing is the antibacterial dressing Sterile dressings are designed with the idea that they will help the wound recover faster than doing nothing. They can stop bleeding and soak up prior fluid loss, help keep the wound free of infection and damage, and help in the healing of the wound.