Biochemistry
Biochemistry is the study of chemical processes within and relating to living organisms. Biochemical processes add to the complexity of life through biochemical signaling and the flow of chemical energy. There are many different aspects to biochemistry, one being the medical field; or more specifically neuroscience. There are many clinical trials happening around the world that include biochemical processes.

Poliovirus Injection To Save A Girl's life
One example is of a 20 year old college student, Stephanie Lipscomb. Stephanie was diagnosed with a stage four glioblastoma multiforme.
Given only a few months to live, Stephanie underwent surgery to remove the tumor, followed by chemotherapy and radiation. It returned within two years. She agreed to take part in the first phase of a research trial at Duke, during which a modified poliovirus was injected directly into the brain tumor. The investigational approach was first discovered by Matthias Gromeier, MD, an associate professor of neurosurgery and molecular genetics at Duke. He discovered that the poliovirus could kill cancer cells while leaving healthy cells unharmed.

According to the American Cancer Society, it is estimated that in 2014, 1,665,540 new cases of cancer will be diagnosed in the United States.
Further, cancer is considered the second leading cause of death leading to the loss of 1 out of every 4 American lives. With these new discoveries, people who have the vaccine for polio could possibly be cancer free in as little as a year.

The 6 1/2 hour polio virus treatment underwent by Lipscomb, known as PVS-RIPO, required the drilling of a small hole into her skull followed by insertion of a catheter. Injections of the polio virus were carried by the catheter directly to the location of the brain tumor.
Lipscomb’s tumor shrunk to the size of a pea, and a series of scans 14 months following the clinical trial treatment have shown no sign of subsequent tumor growth. Below is an image of Lipscomb's scans 14 months apart. The image on the left depicts her scan before the injection, and the image on the right depicts her scan 14 months after the injection.

brain2.jpg

GBM.jpg

How was it done?

The Agent: PVSRIPO is the live attenuated, oral (SABIN) serotype 1 poliovirus (PV) vaccine containing a heterologous internal ribosomal entry site (IRES) from human rhinovirus type 2 (HRV2).
PVSRIPO recognizes Necl-5, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy, e.g. glioblastoma multiforme (GBM), as the host cell receptor.
PVSRIPO has been manufactured at NCI-Frederick, NCI, NIH.

Catheter Implantation: PVS-RIPO will be delivered directly into the tumor.
A stereotactic biopsy will be performed prior to virus administration for frozen section confirmation of viable tumor and further analysis.
The biopsy needle will be placed with stereotactic guidance by an MRI-compatible, stereotactic head frame.
Immediately following the stereotactically-guided tumor biopsy, a catheter will be implanted in the OR at a site different from that used for the biopsy. A CT or MRI scan may be used to confirm catheter placement post-operatively.

Agent infusion: The entire volume of the agent to be delivered will be pre-loaded into a syringe by the investigational pharmacist and connected to the catheter under sterile conditions in the OR at the time of the biopsy procedure.
Patients will be infused through a Medfusion 3500 infusion pump pre-programmed to a delivery rate of 0.5 l/hr.
The total amount of the inoculum delivered to the patient will be 3 ml.
The virusinjection procedure will be completed within 6.5 hrs.
The catheter will be removed immediately following the delivery of PVSRIPO.

Biopsy sampling and analyses: Biopsy material will be obtained from tumor tissue prior to virus administration.

To learn more about Dr. Mathius Gromeier's lab and this clinical trial visit:
http://neuro.surgery.duke.edu/gromeier


brain tumor pic.jpg






Alyssa - Above you talk about how this polio virus injection is in the research stage, is there a reason it hasn't been approved yet to start actually treating patients? If so why, is there a negative effect when used the polio virus injection? Above you also talk about a patient named Stephanie and no other patients, are there more positive cases like this one, or has she been the only one that ended with a good outcome?
Elizabeth- Stephanie is the first and only patient that this has been tried on so far. Injecting this disease into someone's body is very dangerous, seeing how it can lead to paralysis or death. Dr. Gromeier has been researching for 20 years before he tried this on a patient. The risks in this trial are significantly high, but done correctly, the cancer cells are terminated and the healthy cells are kept safe.
Kourtnei- Would the injection of the polio virus into the brain be considered a form of gene therapy? Also, do you know if this this type of treatment work with other parts of the body, or is it limited only to the brain? Expanding further on Alyssa's question- Are there currently any other patients who are in the middle of the process of this clinical trial? What are the requirements necessary for a patient to be considered an ideal candidate for this trial?
Elizabeth- Yes, injecting the poliovirus into the brain would be considered a form of gene therapy. This type of treatment at the moment is currently restricted to the brain. Doctors have found a certain place in the brain to inject the catheter that will not harm the brain or any other part of the body. As of this moment, there are no other patients in the middle of this process simply because the doctors were waiting to see the results of this one. Because the results were so positive after 14 months, doctors expect many other applicants soon. So far for this trial, a patient must be diagnosed with a stage four glioblastoma multiforme. The patient's life expectancy will determine if they are treated sooner rather than later.
Zoë- You said above that the risks for performing this treatement are rather high. What are these risks? Does the virus have a potential to harm our brains, or is are the risks solely into human error? Does the brain not go into shock from the injection of a foreign virus into it, like does the brain have any reaction/ change that could lead to believe in any issues involved with the injection?
Olivia D. - What makes polio the best virus to inject into the tumors? Have there been any studies or clinical trials on other viruses? If so, what were they and how successful were the attempts?

In reading your paper I have found a few similarities with my own. These include using foreign DNA to fix internal problems and also inserting new DNA and compounds into pre-existing cells in the body. In this case polio was inserted into the body. Instead of inserting a deadly disease, would it be possible to use recombinant DNA in the form of somatic gene therapy to fix, or cut off the cancer cells from the rest of the body? Maybe new DNA could be inserted that kills the cancer cells but is not as harmful or as dangerous as polio?
-Cole K.


http://www.dukemedicine.org/
http://www.cancer.duke.edu/btc/modules/Research3/index.php?id=41
http://www.ksdk.com/story/news/health/2014/04/28/stephanie-lipscomb-cancer-poliovirus/8442841/
http://www.king5.com/health/Poliovirus-kills-brain-cancer-tumor-257149671.html
http://www.futurity.org/polio-virus-engineered-to-kill-brain-tumor/