The Future of Medicine: Non-Invasive Nerve Repair

neuronsRepairing severed nerves remains one of the most challenging aspects of modern medicine. In addition to being common, due to spinal injuries, pressure or stretching, the severing or damaging of nerves can lead to a loss of mobility as well as sensation. And up until recently, doctors hoping to repair the damage have been heavily reliant on long-term methods that can be expensive and invasive.

However, Professor George Bittner and his colleagues at the University of Texas at Austin Center for Neuroscience have developed a new and inexpensive procedure to quickly repair severed peripheral nerves. Taking advantage of a mechanism similar to that which permits many invertebrates to regenerate and repair damaged nerves, the new procedure involves applying healing compounds directly to the severed nerve ends.

nerveTrauma to peripheral nerves, which connect the central nervous system to the muscles and sensory organs, is quite common, and is usually the result of excessive pressure or stretching. In most cases, this means that the axon of a nerve – the central bundle of cylindrical sheaths that contains individual nerve cells – is separated from the nerve fiber, leaving the nerve intact but disconnected from the muscle.

Afterward, the nerve cell slowly begins to regrow, and can form a twisted ball of nerve fiber at the cut in the axon. Such nerve scars are called neuroma, and in current medical practice, they are repaired by using microsutures to reconnect the cut ends of the axon and provide a continuous axon to guide the regrowth of the nerve fiber. However, this procedure is extremely delicate, and recovery can take months or even years.

george_bittner1Bittner and his colleagues’ new method involve using a natural healing process to aid in repair and recovery. Already, his team discovered that when a plasma membrane in a cell is damaged, a calcium-mediated healing mechanism begins to draw vesicles (small sacks of lipid membranes) towards the site of the injury. These provide the raw material needed to repair the site.

However, when these vesicles are attracted to the site of a severed axon, both ends of the axon are sealed off by this repair mechanism, preventing regrowth of the nerve. To avoid this problem, the first step of the Texas group’s nerve repair procedure is to bathe the area of the severed nerve with a calcium-free saline solution, thus preventing and even reversing premature healing of the axon ends.

nerve_rootThe damaged axons remain open, and can more easily be reattached. This is then done by pulling the severed ends to within a micron of each other, whereupon a small amount of a solution containing polyethylene glycol (PEG) is injected. The PEG removes water from the axonal membranes, allowing the plasma membranes to merge together, thereby healing the axon.

At the same time, the nerve fibers are brought into close enough proximity that they receive chemical messengers from each other, making them believe they are still whole and preventing the death of the disconnected nerve fiber. The severed nerve fibers can then grow together in a short period of time and with relatively good fidelity to the original connectivity of the nerve fibers.

nerves_pinwheeltestThe final step of the procedure is to inject the area with a calcium-rich saline solution, which restarts the vesicle-based repair mechanism, thereby repairing any residual damage to the axonal membrane. At this point, the nerve is structurally repaired, and use of the affected area begins to return within a few hours instead of months.

To test the procedure, Bittner and his colleges experimented on a series of rats that had had their sciatic nerves severed, resulting in paralysis of the affected limb. In each case, once the rats awoke, they were able to move the limbs containing the severed nerves within moments. Normal function was partially restored within a few days,  nd 80-90% of the pre-injury function was restored within two to four weeks.

mouseThe chemicals used in Bittner’s procedure are common and well understood in interaction with the human body. Because of this, there is no clear obstacle to beginning human clinical trials of the procedure, and teams at Harvard Medical School and Vanderbilt Medical School and Hospitals are currently conducting studies aimed at gaining approval for such trials.

While the procedure developed by Bittner’s group will not apply to the central nervous system or spinal cord injuries, the procedure offers hope to people whose futures include accidents involving damaged nerves. In the past, such people would have to undergo surgery, followed by months or years of physiotherapy (often with inconclusive results).

Now they can look forward to a full recovery that could take as little as a few weeks and cost them comparatively very little. And we, as human beings, would be one step closer to eliminating the term “permanent injury” from our vocabulary!

Sources: gizmag.com, newscientist.com, sciencedaily.com

Ending HIV: New Vaccine Holds Promise for a Cure

hiv-aids-vaccineScientists and researchers have been making great strides in the fight against HIV/AIDS in recent years. In addition to developing vaccines that have shown great promise, there have even been some treatments that have been shown to eliminate the virus altogether. And it seems that with this latest development, which was published in Nature earlier this month, there might be a treatment that can double as a cure.

Developed at the Vaccine and Gene Therapy Institute at the Oregon Health and Science University (OHSU), this new vaccine proved successful in about fifty percent of the clinical subjects that were tested, and may be able to cure patients who are currently on anti-retroviral drugs. If successful, this could mean that a preventative vaccine and cure could come in the same package, thus eliminating HIV altogether.

vaccineCurrently, anti-retroviral drugs and HIV vaccine typically aim at improving the immune response of the patient in the long term. However, they are limited in that they can never completely clear the virus from the body. In fact, aside from a very few exceptional cases, researchers have long believed that HIV/AIDS could only be contained, but not completely cured.

The OHSU team, led by Dr. Louis Picker, has been working on its own vaccine for the past 10 years. In that time, their research has shown that an immune response can in fact go beyond containment and systematically wipe the virus out of the body. As with most early vaccine candidates, the study revolves around SIV – a more aggressive virus than HIV that can replicate up to 100 times faster and, unchecked, can cause AIDS in only two years.

HIV_virusPicker and his research team created the vaccine by working with cytomegalovirus (CMV), another virus which is itself persistent, but doesn’t cause disease. In their initial tests, the vaccine was found to generate an immunoresponse very similar to that generated by CMV, where T-cells that can search and destroy target cells were created and remained in the system, consistently targeting SIV-infected cells until the virus was cleared from the body.

For the sake of their clinical trials, simian subjects were used that were infected by the HIV virus. When treated with the team’s vaccine, half of the subjects initially showed signs of infection, but those signs gradually receded before disappearing completely. This sets it apart from other vaccines which also generate an immunoresponse, but one which fades over time.

HIVAccording to Dr. Picker, it is the permanency of the T-cells that allows the immunoresponse to be consistent and slowly eradicate the virus, eventually eliminating it completely from the system. Says Dr. Picker of their trials and the possibilities for the vaccine:

The virus got in, it infected some cells, moved about in various parts of the body, but it was subsequently cleared, so that by two or three years later the monkeys looked like normal monkeys. There’s no evidence, even with the most sensitive tests, of the SIV virus still being there... We might be able to use this vaccine either to prevent infection or, potentially, even to apply it to individuals who are already infected and on anti-retroviral therapy. It may help to clear their infections so ultimately they can go off the drugs.

Currently, Picker and his the team are trying to understand why some of the vaccinated animals did not respond positively, in the hopes of further increasing the efficacy of the vaccine. Once these trials are complete, it could be just a hop, skip and a jump to getting FDA approval and making the vaccine/cure available to the open market.

Cure_for_HIVImagine, if you will, a world where HIV/AIDS is on the decline, and analysts begin predicting how long it will take before it is eradicated entirely. At this rate, such a world may be just a few years away. For those working in the field of medicine, and those of us who are around to witness it all, it’s an exciting time to be alive!

And be sure to enioy this video from OHSU where Dr. Picker speak about their vaccine and the efforts to end HIV:


Sources:
gizmag.com, nature.com

Ending Cancer: “Canary” and Microscopic Velcro

cancer_cellEnding terminal illness is one of the hallmarks of the 21st century, with advances being made all the time. In recent years, efforts have been particularly focused on findings treatments and cures for the two greatest plagues of the past 100 years – HIV and cancer. But whereas HIV is one of the most infectious diseases to ever be observed, cancer is by far the greater killer. In 2008 alone, approximately 12.7 million cancers were diagnosed (excluding non-invasive cancers) and 7.6 million people died of cancer worldwide.

Little wonder then why so much time and energy is dedicated to ending it; and in recent years, a number of these initiatives have begun to bear fruit. One such initiative comes from the Mayo Clinic, where researchers claim they have developed a new type of software that can help classify cancerous lung nodules noninvasively, thus saving lives and health care costs.

lung-cancer-treatmentIt’s called Computer-aided Nodule Assessment and Risk Yield, or Canary, and a pilot study of the software recently appeared in the April issue of the Journal of Thoracic Oncology. According to the article, Canary uses data from high-resolution CT images of a common type of cancerous nodule in the lung and then matches them, pixel for pixel, to one of nine unique radiological exemplars. In this way, the software is able to make detailed comparisons and then determine whether or not the scans indicate the presence of cancer.

In the pilot study, Canary was able to classify lesions as either aggressive or indolent with high sensitivity, as compared to microscopic analyses of the lesions after being surgically removed and analyzed by lung pathologists. More importantly, it was able to do so without the need for internal surgery to allow a doctor to make a visual examination. This not only ensures that a patient could receive and early (and accurate) diagnosis from a simple CT scan, but also saves a great deal of money by making surgery unnecessary.

velcroAs they say, early detection is key. But where preventative medicine fails, effective treatments need to be available. And that’s where a new invention, inspired by Velcro comes into play. Created by researchers at UCLA, the process is essentially a refined method of capturing and analyzing rogue cancer cells using a Velcro-like technology that works on the nanoscale. It’s called NanoVelcro, and it can detect, isolate, and analyze single cancer cells from a patient’s blood.

Researchers have long recognized that circulating tumor cells play an important role in spreading cancer to other parts of the body. When the cells can be analyzed and identified early, they can offer clues to how the disease may progress in an individual patient, and how to best tailor a personalized cancer treatment. The UCLA team developed the NanoVelcro chip (see above) to do just that, trap individual cancer cells for analysis so that early, non-invasive diagnosis can take place.

NanoVelcro-deviceThe treatment begins with a patient’s blood being pumped in through the NanoVelcro Chip, where tiny hairs protruding from the cancer cells stick to the nanofiber structures on the device’s surface. Then, the scientists selectively cut out the cancer cells using laser microdissection and subject the isolated and purified cancer cells to single cell sequencing. This last step reveals mutations in the genetic material of the cells and may help doctors personalize therapies to the patient’s unique form of cancer.

The UCLA researchers say this technology may function as a liquid biopsy. Instead of removing tissue samples through a needle inserted into a solid tumor, the cancer cells can be analyzed directly from the blood stream, making analysis quicker and easier. They claim this is especially important in cancers like prostate, where biopsies are extremely difficult because the disease often spreads to bone, where the availability of the tissue is low. In addition, the technology lets doctors look at free-floating cancer cells earlier than they’d have access to a biopsy site.

Already, the chip is being tested in prostate cancer, according to research published in the journal Advanced Materials in late March. The process is also being tested by Swiss researchers to remove heavy metals from water, using nanomaterials to cling to and remove impurities like mercury and heavy metals. So in addition to assisting in the war on cancer, this new technology showcases the possibilities of nantechnology and the progress being made in that field.

Sources: news.cnet.com, fastcoexist.com