Category Archives: Spinal Cord Repair

Neuronal cells may be repaired in the near future opening the potential to reverse brain damage, spinal cord injuries and the devastating effects of diseases such as MS, ALS, Parkinson’s, Dementia and Alzheimer.  For the first time researchers have direct evidence that viruses can infect neuronal cells, raising hope that antiviral therapy might be effective against neurologic diseases and cell damage, according to a new study.

A neurological disorder is any disorder of the body nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor coordination, loss of mental control, sensation, seizures, confusion, pain and altered levels of consciousness

Neurons are nerve cells that transmit nerve signals to and from the brain at up to 200 mph. The neuron consists of a cell body (or soma) with branching dendrites (signal receivers) and a projection called an axon, which conduct the nerve signal. At the other end of the axon, the axon terminals transmit the electro-chemical signal across a synapse (the gap between the axon terminal and the receiving cell). The word “neuron” was coined by the German scientist Heinrich Wilhelm Gottfried von Waldeyer-Hartz in 1891 (he also coined the term “chromosome”).

There are different types of neuronal cells. They all carry electro-chemical nerve signals, but differ in structure (the number of processes, or axons, emanating from the cell body) and are found in different parts of the body.

• Sensory neurons or Bipolar neurons carry messages from the body’s sense receptors (eyes, ears, etc.) to the CNS. These neurons have two processes. Sensory neuron account for 0.9% of all neurons. (Examples are retinal cells, olfactory epithelium cells.)
• Motoneurons or Multipolar neurons carry signals from the CNS to the muscles and glands. These neurons have many processes originating from the cell body. Motoneurons account for 9% of all neurons. (Examples are spinal motor neurons, pyramidal neurons, Purkinje cells.)
• Interneurons or Pseudopolare (Spelling) cells form all the neural wiring within the CNS. These have two axons (instead of an axon and a dendrite). One axon communicates with the spinal cord; one with either the skin or muscle. These neurons have two processes. (Examples are dorsal root ganglia cells.)

The core component of the nervous system in general, and the brain in particular, is the neuron or nerve cell, the “brain cells” of popular language. A neuron is an electrically excitable cell that processes and transmits information by electro-chemical signalling. Unlike other cells, neurons never divide, and neither do they die off to be replaced by new ones. By the same token, they usually cannot be replaced after being lost, although there are a few exceptions.

Information transmission within the brain, such as takes place during the processes of memory encoding and retrieval, is achieved using a combination of chemicals and electricity. It is a very complex process involving a variety of interrelated steps, but a quick overview can be given here.

Unlike other body cells, most neurons in the human brain are only able to divide to make new cells (a process called neurogenesis) during fetal development and for a few months after birth.
These brain cells may increase in size until the age of about eighteen years, but they are essentially designed to last a lifetime.

During childhood, and particularly during adolescence, a process known as “synaptic pruning” occurs.
Although the brain continues to grow and develop, the overall number of neurons and synapses are reduced by up to 50%, removing unnecessary neuronal structures and allowing them to be replaced by more complex and efficient structures, more suited to the demands of adulthood.

The data demonstrate that Epstein Barr Virus (EBV) and Kaposi’s sarcoma–associated herpesvirus (KSHV) are able to effectively infect neuronal cell lines, as well as primary neurons. “This phenomenon may potentially provide clues to their contribution to the pathogenesis of human neural diseases,” stated the researchers, led by senior author Erle S. Robertson, PhD, of the University of Pennsylvania in Philadelphia, PA.

“In this study, for the first time, we have successfully demonstrated the in vitro infection of Sh-Sy5y (a human neuroblastoma cell line) and Ntera2 cells (a neuronally committed human teratocarcinoma cell line), as well as human primary neurons. We have also determined that the infection is predominately lytic. Additionally, we also report infection of neuronal cells by KSHV in vitro similar to that by EBV,” stated the authors.

They believe that these findings may “open new avenues of consideration related to neuronal pathologies and infection with these viruses. Furthermore, their contribution to chronic infection linked to neuronal disease will provide new clues to potential new therapies.”

In many debilitating neurodegenerative diseases, including MS, the efficiency of electrochemical signals is greatly reduced, they noted, often leading to problems related to cognition and muscular activity. “It is likely that viral infection with EBV or KSHV may severely reduce these signals, leading to reduced cognition and reduced neuromuscular function,” they stated.

The results clearly show that infection of neuronal cells can occur, but further studies are needed to understand the underlying mechanism of these infections and their relevance to neuronal diseases.

Sources:

http://www.neurologytimes.com/alzheimer-disease/herpes-viruses-infection-neurons#sthash.kOMeJYI8.dpuf

http://www.human-memory.net/brain_neurons.html

http://www.enchantedlearning.com/subjects/anatomy/brain/Neuron.shtml

IT SOUNDS like the dark plot of a vampire movie – Young blood rejuvenates our cells. In October 2014, people with Alzheimer’s disease started to be injected with the blood of young people in the hope that it will reverse some of the damage caused by that condition. But holds promise for individuals suffering for a wide range issues that have impacted their body and effected the quality of their life style. Just imagine the implications of reversing Traumatic Brain Injuries, Parkinson’s, MS, ALS, Repairing Damaged Organs, Surgical Healing, Aging of Skin, Muscle and Vascular Development.

In the first human trial of the effects of young blood, at Stanford University, infusions of blood plasma from young people are being given to older people. The preliminary results have surprised the research team, since it appears that young blood rejuvenates all of the cells within the recipients’ bodies are showing marked improvement.

Blood Stanford Test

The scientists behind the experiment have evidence on their side that young blood rejuvenates. Work in animals has shown that a transfusion of young mouse blood can improve cognition and the health of several organs in older mice. It could even make those animals look younger. The ramifications for the cosmetics and pharmaceutical industries could be huge, if the same thing happens in people.

The study was published in Nature Medicine in 2014. Immediately, emails flooded in to Wyss-Coray’s inbox. Alzheimer’s patients wanted infusions of young blood. So did numerous aged billionaires interested in the potential that young blood rejuvenates. One, who flies around in a jet with his name emblazoned on the side, invited Wyss-Coray to an Oscars after-party this year. (He didn’t go.) Another correspondent wrote with a more disturbing offer: he said he could provide blood from children of whatever age the scientists required. Wyss-Coray was appalled. “That was creepy,” he said.

But it wasn’t until spring 2012 that plans to form a company emerged. Nikolich, an entrepreneur and neuroscientist at Stanford, had flown to Hong Kong to visit the family of Chen Din-hwa, a Chinese billionaire known as the King of Cotton Yarn. Three years earlier, Chen had died, aged 89, with Alzheimer’s disease. His grandson told Nikolich that towards the end of his life, Chen barely recognised his own family. Then he had a plasma transfusion for an unrelated condition, which seemed to have a spectacular effect. His mind was clearer and he was suddenly cogent. His grandson indicated that Alzheimer’s disease seem to historical effect the male of the family often at an early age.

Nikolich told them about Wyss-Coray’s research and the potential for plasma-based therapies that revitalised the ageing brain. Before long, the conversation turned to starting a company. The family invested a year later. The money got Alkahest established and ready to launch the first human trial of young plasma.

Alkahest’s ultimate goal – to identify the key proteins in plasma that rejuvenate or age human tissues and then manufacture a product that uses them – could take 10 to 15 years. In the near term, the company has another strategy. Earlier this year, the Spanish blood products firm, Grifols, pledged $37.5m for a 45% stake in Alkahest. With another $12.5m, the company will bankroll more research in exchange for rights to Alkahest’s first products. Over the next two years, Alkahest will take human plasma and divide it into fractions that are rich in different proteins. Each fraction will then be tested in mice to see if they boost brain function. Any that do will be swiftly introduced into human trials and developed into the first generation of products.

The Alkahest trial is small. Sha, a specialist in behavioral neurology, can enroll only 18 people aged 50 to 90 with mild to moderate Alzheimer’s disease. Each receives a unit of young human plasma or saline once a week for four weeks. They have the next six weeks off, then have four more weeks of infusions. Those who had plasma first time around get saline and vice versa. The process is blinded, so neither the patients, nor their carers, nor Sha herself, know who is receiving what. Throughout the trial, doctors will look for cognitive improvements. Only at the end of the trial, as soon as October this year, will Sha analyse the findings.

If patients improve with infusions of young plasma, scientists will be ecstatic. But the finding, indicating that young blood rejuvenates, would need to be replicated, ideally at other hospitals, and in more patients, in order to convince researchers. If any benefits stand the test of time, the studies will move on, to tease out the best doses and ages at which to give plasma, how patients’ brains change, and whether improvements make a real difference to the life of someone who can no longer recognize their own family.

Then there is safety. Toying with the ageing process might backfire. Rando is concerned that pumping pro-youthful proteins into people for years could end up giving them cancer. Wyss-Coray agrees it is a worry, but points out that long-term growth hormone therapy appears to be safe. “We just don’t know yet whether or not it will be a problem,” he said.

Rando is more upbeat about infusing patients with pro-youthful proteins for short periods. An elderly person having surgery might get an infusion to help them heal like a teenager. “Let’s say it works. If you can target tissues and improve wound healing in older people, that would be a feasible approach. It would not be about making 90-year-olds younger, or having people live to 150. It’s about healthy living, not longer living,” he said.

In the first human trial of the effects of young blood, at Stanford University, infusions of blood plasma from young people are being given to older people. The preliminary results have surprised the research team, since it appears that all of the cells within the recipients’ bodies are showing marked improvement.

In some countries, there is already a legal market for blood plasma. In the wake of the BSE crisis of the 1990s, plasma donations are not used in the UK. But in the US, donors can make $200 a month (plus loyalty points) from plasma donations. The fresh plasma is separated from the blood, and the red blood cells returned to the bloodstream, in a sitting that lasts 90 minutes. The plasma is used in medical procedures, to treat coagulation disorders and immune deficiencies. The business is completely legitimate, but if young blood rejuvenates our cells is proved to have anti-ageing effects, the risk of backstreet operators setting up will soar. When I asked Wyss-Coray if the prospect worried him, he looked serious. “Absolutely,” he said. “There are always going to be nutcases.”

These are worst-case scenarios. The Stanford trial may find that simply injecting young plasma into old people has little or no effect. Wyss-Coray confesses that he suspects as much. He believes that rejuvenating older people might take a more potent brew than natural plasma. He has in mind a concentrated blend of 10 or 20 pro-youthful factors from young blood, mixed with antibodies that neutralise the effects of ageing factors found in old blood.

“As we get older, we have fewer stem cells and newly born neurons in our brains, and our learning and memory are affected,” says Villeda. “It’s not ddementia it’s just the natural degeneration associated with age.”

Amy Wagers emphasizes that no one has convincingly shown that young blood lengthens lives, and there is no promise that it will. Still, she says that young blood, or factors from it, may hold promise for helping elderly people to heal after surgery, or treating diseases of ageing.

Young mice blood has been studied to cause repair of age related damage such as cardiac hypertrophy, muscle dysfunction, demyelination processes and brain vasculature system in old mice. The mouse is the most common model organism for preclinical studies even though it has not proven particularly reliable at predicting the outcome of studies in humans.

Wyss-Coray one of the authors of the study mentioned in the question is a part of board of directors of a biotechnology start-up named Alkahest to explore the therapeutic implications of the mice findings in humans. The young mice blood treatment has been shown to have effects in old mice neural dysfunctions such as

1. Cardiac hypertrophy: Loffredo et.al. have concluded that treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging in 2013.

2. Muscle dysfunction: GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction per conclusions of Sinha M et.al. in 2014.

3. Reversal of demyelination processes: Ruckh JM et.al. in 2012 concluded that enhanced remyelinating (Remyelination is a term for the re-generation of the nerve’s myelin sheath, damaged in many diseases) activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life.

4. Improvement of brain vasculature system: Katsimpardi L et.al. in 2014 concluded that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. Studies in mice and Xenopus suggest that this protein is involved in mesodermal formation and neurogenesis during embryonic development. Research shows that there could be multiple forms of GDF11

Sources:

http://www.nature.com/news/ageing-research-blood-to-blood-1.16762

Home

http://glennlaboratories.stanford.edu/

http://www.nature.com/news/blood-hormone-restores-youthful-hearts-to-old-mice-1.12971

http://www.bizjournals.com/sanfrancisco/print-edition/2014/01/31/conboy-uc-berkeley-aging-research.html

http://www.bizjournals.com/sanfrancisco/blog/biotech/2014/05/young-blood-stanford-researchers-hope-plasma.html

http://www.bizjournals.com/sanfrancisco/print-edition/2014/01/31/aging-calico-levinson-buck-institute.html

https://www.ucsf.edu/news/2014/01/122211/blood-work-scientists-uncover-surprising-new-tools-rejuvenate-brain

https://www.newscientist.com/article/mg22329831-400-young-blood-to-be-used-in-ultimate-rejuvenation-trial/

http://www.theguardian.com/science/2015/aug/04/can-we-reverse-ageing-process-young-blood-older-people

The spinal cord regenerated with nasal cells was pioneered by Prof. Geoffrey Raisman, who first identified their potential to repair nerve damage in mice. The olfactory en-sheathing cell transplantation has been successfully used to enable Darek Fidyka, who was paralyzed from the chest down in a knife attack in 2010, to walk again.

The future for cell regeneration is extremely vast according to Professor Geoffrey Raisman, who began experimenting with mice in this field with his first transplant in 1972, over 40 years ago. In years to come, utilizing his team’s first successful human regenerative cell transplant, as an initial first step, we will see strides made in stroke, heart and brain damage patients. The horizon is vast for the improvement of humanities health and well being.

http://youtu.be/OMJLg5K40U0

The paper reporting the transplant, which was carried out by surgeons in Poland and  led by Geoffrey Raisman of the UCL Institute of Neurology, is published today in the journal Cell Transplantation (5). The technique involves taking specialized cells known as olfactory ensheathing cells (OECs) from the patient’s own patient’s olfactory bulbs, and then grafting these cells at the site of injury, where they promote nerve cell growth to bridge the gap and restore function. An added advantage in using the patient’s own cells is that it avoids the problem of rejection by their immune system.

Darek Fidyka, 40, from Poland, said walking again – with the support of a frame – was “an incredible feeling”, adding: “When you can’t feel almost half your body, you are helpless, but when it starts coming back it’s like you were born again.”

Prof Geoffrey Raisman, chair of neural regeneration at University College London’s Institute of Neurology, led the UK research team. He said what had been achieved was “more impressive than man walking on the moon“.

The treatment used olfactory ensheathing cells (OECs) – specialist cells that form part of the sense of smell. OECs act as pathway cells that enable nerve fibres in the olfactory system to be continually renewed. In the first of two operations, surgeons removed one of the patient’s olfactory bulbs and grew the cells in culture.

Two weeks later they transplanted the OECs into the spinal cord, which had been cut through in the knife attack apart from a thin strip of scar tissue on the right. They had just a drop of material to work with – about 500,000 cells. About 100 micro-injections of OECs were made above and below the injury with four thin strips of nerve tissue were taken from the patient’s ankle and placed across an 8mm (0.3in) gap on the left side of the cord.

The scientists believe the OECs provided a pathway to enable fibres above and below the injury to reconnect, using the nerve grafts to bridge the gap in the cord.

BBC Interview by Fergus Walsh with UK research team