Jan 17, 2016

Is the post-polio syndrome due to chronic poliovirus infection?

Over the years, poliomyelitis survivors may experience e progressive decline of physical strength accompanied by intolerance to cold, chronic pain and other disabilities. This condition, termed post-polio syndrome (PPS), may lead to the incapacity of living an independent life, generates suffering and considerable social costs. PPS usually arises after many years of partial/complete functional recovery with apparently stable neuromuscular functions. In developed countries, in fact, it is common experience that polio patients had a productive life before starting to experience PPS at the time of retirement. PPS is estimated to affect about 20 million people worldwide.
Fig. 1. Predicted age distribution of polio survivors in the USA in the years 2006 and 2016 (source: Becker LC. Polio survivors in the U.S., 1915–2000. Age distribution data. Saint Louis, MO: Post-Polio Health International; 2006).
In the article, the estimated epidemiology of PPS is reported together with the pathogenic pathways that could lead, over time, to the progressive loss of neuromuscular functions. When PPS becomes clinically manifest, polio survivors experience new weakness, generalized fatigue, atrophy of previously unaffected muscles, physical decline.
The core message is that PPS can be caused by unapparent chronic low-level infection due to the poliovirus type that, at the time of the initial insult, infected the patient. This conclusion is derived from the study of about 120 PPS patients. Nearly three quarters of them were shown to harbor poliovirus “remnants” (in other words polioviral genomes and low-level virus activity). It is thought that chronic virus infection of the nervous and muscular systems may be responsible of the progressive loss of neural and muscular cells that is accompanied by low-level chronic inflammation.
An important point is that the “poliovirus remnants” detected in PPS patients are not transmitted to family members, thus are not dangerous to the population, nor represent a possible form of resurrection for poliomyelitis. It is thought, but not proven, that the poliovirus forms that remain persistent in polio survivors are “mutated” or “genetically changed” derivatives of the virulent polioviruses that were circulating (before anti-polio vaccines) at the time of polio epidemics.
Idealized representation of changes in motor units from the time of acute poliovirus
Fig. 2. Idealized representation of changes in motor units from the time of acute poliovirus attack and the possible development of PPS. Distal degeneration of innervating fibres and loss of motor units accompanies the appearance of new weakness and the atrophy of previously unaffected muscles.
Finally, the need is presented for an effective “cure” of PPS. So far, in fact, anti-inflammatory drugs and other treatments have failed in this field. A possible remedy is seen in the administration of intravenous human immunoglobulins (i.e., antibodies derived from blood donors). This treatment is costly and only temporarily effective. For this reason, the article brings the attention of clinicians and pharma industries to the need of introducing antiviral agents for the treatment of this condition. Several new antiviral compounds are becoming available, and some of them have the potential of blocking the replication and pathogenicity of polioviruses. Treatment of PPS cases with select compounds could ameliorate the life of patients, and could serve as a test for using these same compounds as drugs for new poliovirus epidemics that might emerge in the world.
Antonio Toniolo
University of Insubria Medical School, Varese, Italy

Jan 12, 2016

Neuroprosthetics for paralysis: an new implant on the spinal cord

EPFL scientists have managed to get rats walking on their own again using a combination of electrical and chemical stimulation. But applying this method to humans would require multifunctional implants that could be installed for long periods of time on the spinal cord without causing any tissue damage. This is precisely what the teams of professors Stéphanie Lacour and Grégoire Courtine have developed. Their e-Dura implant is designed specifically for implantation on the surface of the brain or spinal cord. The small device closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and pharmacological substances. The risks of rejection and/or damage to the spinal cord have been drastically reduced. An article about the implant will appear in early January in Science Magazine.

So-called “surface implants” have reached a roadblock; they cannot be applied long term to the spinal cord or brain, beneath the nervous system’s protective envelope, otherwise known as the “dura mater,” because when nerve tissues move or stretch, they rub against these rigid devices. After a while, this repeated friction causes inflammation, scar tissue buildup, and rejection.

An easy-does-it implantFlexible and stretchy, the implant developed at EPFL is placed beneath the dura mater, directly onto the spinal cord. Its elasticity and its potential for deformation are almost identical to the living tissue surrounding it. This reduces friction and inflammation to a minimum. When implanted into rats, the e-Dura prototype caused neither damage nor rejection, even after two months. More rigid traditional implants would have caused significant nerve tissue damage during this period of time.

The researchers tested the device prototype by applying their rehabilitation protocol -- which combines electrical and chemical stimulation – to paralyzed rats. Not only did the implant prove its biocompatibility, but it also did its job perfectly, allowing the rats to regain the ability to walk on their own again after a few weeks of training.

“Our e-Dura implant can remain for a long period of time on the spinal cord or the cortex, precisely because it has the same mechanical properties as the dura mater itself. This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury,” explains Lacour, co-author of the paper, and holder of EPFL’s Bertarelli Chair in Neuroprosthetic Technology.

Flexibility of tissue, efficiency of electronicsDeveloping the e-Dura implant was quite a feat of engineering. As flexible and stretchable as living tissue, it nonetheless includes electronic elements that stimulate the spinal cord at the point of injury. The silicon substrate is covered with cracked gold electric conducting tracks that can be pulled and stretched. The electrodes are made of an innovative composite of silicon and platinum microbeads. They can be deformed in any direction, while still ensuring optimal electrical conductivity. Finally, a fluidic microchannel enables the delivery of pharmacological substances – neurotransmitters in this case – that will reanimate the nerve cells beneath the injured tissue.

The implant can also be used to monitor electrical impulses from the brain in real time. When they did this, the scientists were able to extract with precision the animal’s motor intention before it was translated into movement.

“It’s the first neuronal surface implant designed from the start for long-term application. In order to build it, we had to combine expertise from a considerable number of areas,” explains Courtine, co-author and holder of EPFL’s IRP Chair in Spinal Cord Repair. “These include materials science, electronics, neuroscience, medicine, and algorithm programming. I don’t think there are many places in the world where one finds the level of interdisciplinary cooperation that exists in our Center for Neuroprosthetics.”

For the time being, the e-Dura implant has been primarily tested in cases of spinal cord injury in paralyzed rats. But the potential for applying these surface implants is huge – for example in epilepsy, Parkinson’s disease and pain management. The scientists are planning to move towards clinical trials in humans, and to develop their prototype in preparation for commercialization.
Author:Lionel PousazSource:Mediacom
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