Digging deep down to molecules

Scientists pinpoint molecular signal that drives and enables spinal cord repair

Caption: This is a confocal micrograph taken from the lesion core after a spinal cord injury. Nuclear EdU (red) shows the presence of newly differentiated cells which produce Schwann cell myelin (P0, green). These peripheral-like Schwann cells remyelinate central axons in the injured spinal cord and are important for spontaneous repair and functional recovery after spinal cord injury.
Researchers from King’s College London and the University of Oxford have identified a molecular signal, known as ‘neuregulin-1’, which drives and enables the spinal cord’s natural capacity for repair after injury.
The findings, published today in Brain, could one day lead to new treatments which enhance this spontaneous repair mechanism by manipulating the neuregulin-1 signal.
Every year more than 130,000 people suffer traumatic spinal cord injury (usually from a road traffic accident, fall or sporting injury) and related healthcare costs are among the highest of any medical condition – yet there is still no cure or adequate treatment.
Spinal cord injury has devastating consequences for muscle and limb function, but the central nervous system does possess some limited capacity to repair itself naturally.
Understanding what drives this repair mechanism could aid the development of new treatment strategies aimed at boosting the self-healing capacity of the injured spinal cord by taking advantage of ‘tools’ that the spinal cord already possesses.
For the first time researchers from King’s and Oxford have identified one of these tools, neuregulin-1, which signals from the surface of damaged nerve fibres during a process called ‘spontaneous remyelination.’
Spontaneous remyelination is a period of natural regeneration that happens in the weeks following a spinal cord injury. The process takes place as a result of damage to spinal nerve fibres which have lost their insulating ‘myelin sheath’. This myelin sheath is crucial for efficient communication between the brain and the body.
However, this natural capacity for repair is not sufficient for full recovery and may account for the compromised function of surviving nerve fibres, which can affect balance, coordination and movement.
The researchers found that, in mice lacking the neuregulin-1 gene, spontaneous myelin repair was completely prevented and spinal nerve fibres remained demyelinated (i.e. unable to send nerve signals along the spinal cord).
They also discovered that mice without neuregulin-1 showed worse outcomes after spinal cord injury compared to mice with the gene intact, particularly in walking, balance and coordinated movements.
Not only did neuregulin-1 drive spontaneous remyelination, but it also served as a molecular switch for cells within the spinal cord to transform themselves into cells with remyelinating capacity. This is unusual, according to the researchers, because the ‘Schwann’ cells with new remyelinating capacity normally only myelinate nerve fibres in the peripheral nervous system – not the central nervous system, as observed here.
Elizabeth Bradbury, Professor of Regenerative Medicine & Neuroplasticity at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, and Medical Research Council Senior Fellow, said: ‘Spinal cord injury could happen to anyone, at any time. In an instant your life could change and you could lose all feeling and function below the level of the injury.
‘Existing treatments are largely ineffective, so there is a pressing need for new regenerative therapies to repair tissue damage and restore function after spinal cord injury.
‘These new findings advance our understanding of the molecular mechanisms which may orchestrate the body’s remarkable capacity for natural repair.’

Professor Bradbury added: ‘By enhancing this spontaneous response, we may be able to significantly improve spinal cord function after injury. Our research also has wider implications for other disorders of the central nervous system which share this demyelinating pathology, such as multiple sclerosis.’
Dr Katalin Bartus, also from the IoPPN at King’s College London, said: ‘We hope this work will provide a platform for future research, in which it will be important to test how enhancing levels of neuregulin-1 will improve functional outcome after spinal cord injury.’
This research is a collaboration between scientists at King’s – led by Professor Elizabeth Bradbury – who work on repairing traumatic injuries of the central nervous system, and a group of researchers at Oxford – led by Professor David Bennett – who work on nerve injury and myelination within the peripheral nervous system. The study was funded by the Medical Research Council, Wings for Life Spinal Cord Research Foundation, the Wellcome Trust and the International Spinal Research Trust and Henry Smith Charity.



Exciting News from Dr. Silver’s Lab

When Spinal Cord Injury occurs, our body creates a scar in that area of spinal cord. This “crust” forms a solid wall that still sprouting neurons can not overcome. The idea behind Dr. Silver’s work is to find a way to dissolve this scar and help neurons from both sides of injury spot to grow and re-connect again.
In the latest appearance in Cleveland, OH @ Neural Prosthesis seminar (January 16, 2016) Dr. Silver has announced results from research on chronic animal model treated with Chondroitinase (Cha’se) enzyme and Peptide, concluding that “robust breathing function recovery occurred”.
Experiment is repeated several times and possibly  first time in medical history we have significant Central Nervous System Regeneration with certain method / therapy confirmed.
Dr. Silver want to rush his team findings from the lab to human use as soon as possible. One intermediate step, as test on large animal model (primates), is needed before the first people with high level SCI injuries (patients using ventilators for breathing) will be approached.

Dr. Silver is also ready to answer any questions at this Post @ CareCure Forum – Click on the Link.   Some of the questions / answers you an read below.

Dogs are already receiving this Cha’se treatment and healing

Quote Originally Posted by comad View Post
Dr Silver, I have few questions:
– What would be the fastest & safest way to deliver Cha’se + Peptide to humans – I guess with micro-injections ?
– If this therapy (to restore breathing) proven effective on humans, do you expect
accelerated human testing for similar Cha’se + Peptide approach for other levels of chronic SCI.
– Also – realistically – how long large animal testing procedure can take?
Thank you very much for your time and for your work!!!!!


Dr. Silver:
Good questions

Ch’ase is administered via micro-injections to the appropriate levels of the cord depending on which behaviors one is targeting for recovery. For breathing, the target is around C4, for arm/hand function C5-8, for walking L2 (the location of the CPG) and bladder/bowel/ sexual function lower lumbar L4,5 + upper sacral. There is a possibility to target multiple cord levels simultaneously with the enzyme. The ISRT is now working on state of the art controlled AAV vector delivery systems for the enzyme. This will give us a long acting, highly potent and widespread delivery system that can be turned off when behavioral improvements plateau. I am extremely optimistic that they will be successful. They are a wonderful and dedicated group. The peptide (or a small molecule substitute that is now being developed) is delivered systemically either via su-cutaneous injections or maybe in the future via oral administration.

I do believe that the respiratory system is not unique in its ability to sprout slowly after injury. I am very optimistic about improving arm/hand function. We should be able to target other levels of the cord as mentioned above. For those with complete cord lesions we will need to build a bridge across the lesion scar and we are now working on that with with a combination of peripheral nerve grafting, Ch’ase and our peptide. We have had great success using our bridging strategy over the years and we are now focused on repeating this in chronic models. The bridging work is funded by a grant from the NIH.

Large animals are a bit of a hurdle due to cost. I have colleagues who are quite interested in testing our strategy in mini-pigs and primates. I would very much like to move to primates before humans because of their human-like hand function. Unfortunately, they are telling me that the cost is about a million and half bucks (100K per animal, good grief). It should not take too long once the experiments begin.

Quote Originally Posted by comad View Post
Thank you for your answers, Dr Silver!
In above quote you’ve said that you will work on building bridges for complete injury.
Is this mean that INCOMPLETE CHRONIC injuries might have even larger chance for recovery using this method? Also, if 1.5 Million (15 animals x $ 100K needed for primates testing step) is obstacle to achieve this research to become human trial – should this community start screaming around for donations and more media attention??!?

Yes, for certain, incomplete chronic injuries are far more likely to respond best to the enzyme. As for money raising it is always appropriate for the SCI community to help call attention to and help raise funds for scientifically excellent research. One good way of identifying the very best SCI related science is to browse the Unite2Fight Paralysis web site. They do a wonderful job of calling attention to the good stuff.

Quote Originally Posted by 6 Shooter View Post

Dr. Silver–Looking down the road after successful large animal trials, when beginning to test with humans, how do you envision the combined Ch’ase and peptides will be administered into the spinal cord? Surgery, injections, pills, intravenous? Oops, just read above which answers this question.

Would this be a one time and done, or would the procedure require multiple attempts due to the time it takes to degrade the glial scar?

The enzyme is administered through micro-needles but the number of injections per area that would adequately cover the cord still needs to be worked out in a larger animal model. In our rat model we only administer a single injection at C4. When the viral vectors are perfected they spread much farther than regular ch’ase. Thus, perhaps only a single injection will be needed even in a larger animal per targeted area. The peptide is given systemically and can be administered for as long as needed. A critical adjunct to the therapy can be physical rehab or epidural stimulation.


SENSOR WALK was developed by Otto Block in conjunction with the Mayo Clinic. The knee-ankle-foot orthotic (KAFO) provides superb stance control for patients who exhibit weak or absent quadriceps, or display knee instability while bearing weight during the stance phase of the gait cycle.

Unique sensors in the footplate know when the patient is in the late stance phase and triggers the knee joint to unlock. Because an extension movement is not required to unlock the joint, the SENSOR WALK helps provide the clinical benefits of a more natural gait. The robust design can handle patients who weigh up to 300 lbs (136 kg) and can accommodate a 15° knee flexion.

Key Features:

Enhanced stability during stance phase.
Stumble recovery due to the ability to block flexion if needed.
The flexion blocking mechanism is activated when needed
during the gait cycle, providing additional stability.
300 lbs (136 kg) weight limit.
Electronic assessment of the relative orientation of the
patient’s limb and utilization of a microprocessor to determine
the appropriate time to engage and disengage the knee joint restraint mechanism.
The SENSOR WALK can be set to function in three ways:
as a locked joint, as a stance control KAF orthotic, and in a free swing mode.

Investment for Cures

NovaGenesis and their Swiss commercial branch Ophiuchus will offer autologous stem cell therapy transplant to investors & family members.
More money in the pocket – closer to the cure folks!!!

Stem cell company tells investors, ‘Make money and save humanity’

A new investment model will see high net worths sponsor ground-breaking research to wipe out the world’s diseases

A small Swiss company has created a novel investment model, where the rewards are far greater than anything financial could bring.

Rather, investors are also paid with technology advancements that could save the lives of their nearest and dearest, or solve their own chronic health issues.

The Novagenesis Foundation and its commercial arm, Ophiuchus Technologies, are pioneers in a niche field of stem cell research. The organisation has created a patented technology that allows bone marrow cells to be taken from an individual, reprogrammed, and reinserted into the body.

The technology is based on the salamander lizard, which can regrow limbs and organs when they are damaged. According to Jørgen Thorball, managing director of Ophiuchus, the company has the capability to heal – and in some cases cure – a variety of health issues.

In Roman mythology, Ophiuchus, also known by his more common name Asclepius, learnt the secrets of keeping death at bay.

The organisations are raising capital through XOventure, which finds funding and support for early-stage life sciences and biotechnology firms.

Ed Cappabianca, senior partner at XOventure, explains that cures are usually avoided by traditional investors, such as venture capitalists, because once someone is cured, the product is no longer required, which limits its scalability.

“What investors want is a single chemical, something like Viagra, that you can scale and sell for a lot of money,” he says. “Once you start taking it, you tend to keep taking it. It doesn’t solve a problem, so you create a customer for life.

Last year Pfizer made $1.7bn from Viagra sales

“The same is true of many treatments for diabetes. The focus is on creating medicines that allow people to lead healthy, happy lives – as long as you keep taking them.”

Novagenesis has been funded by high-net-worth individuals who are motivated by altruistic or personal reasons to further this kind of research. The not-for-profit foundation has already raised “many millions” to take its technology into clinical trials, and Ophiuchus is aiming to close a £7m investment round.

The company could later also go down the crowdfunding route, Cappabianca claimed, allowing armchair investors to invest in the firm. “The early data will help us to secure the next round of funding as we don’t want to IPO too early,” says Cappabianca. “The stock price will be driven up as people hear about us and the last thing you want is to have a steep valuation when you’re looking to raise more money.

“We want to raise money at a lower price, giving early investors a return, but leaving something on the table for the next guy. That way we can keep going back to the well.”

One private investor, Serge Richard, who manages the Swiss branch of a global estate planning business, said he was attracted to the proposition because of its human dimension. “I believe it will create progress for humanity as a whole, not just for a few people,” he says, “Everyone knows somebody who has been hurt in an accident and left disabled or brain damaged and that could all be avoided with this technology.”

Most of Novagenesis’s backing has been provided by a single donor with progressive multiple sclerosis, a form of the disease where symptoms get continually worse over time rather than having relapses and remissions. Cappabianca also got involved with the project because of personal reasons. “A friend has progressive MS,” he says. “I don’t know if we’ll solve the problem in time for Charlie, but it is why I wanted to help raise the money.”

Ophiuchus’s work is currently focused on spinal cord injuries. The foundation’s founder, Jan-Eric Ahlfors, who invented the new technology, chose to target the most severe cases of paraplegics in order to leave no doubt that the science and product concept was robust.

“Most researchers go for the low-hanging fruit,” says Thorball. “But it actually makes sense to try and solve the most difficult problems first because then you know the technology works.”

Ophiuchus has embarked on its first human clinical trials. The trials are being undertaken in Russia, supported by the country’s leading health body, the Federal Research Clinical Centre of Federal Medical & Biological Agency. There will be 30 patients in the current trial.

Ahlfors is working on the core technology in a private lab in Montreal, Canada, and will publish a paper on his research when the current set of clinical trials are complete.

Novagenesis has kept its research under wraps to avoid creating false hope among the paraplegic community, and sufferers of other diseases, who could eventually be helped by the technology. “We didn’t want to create hype before there was a product,” says Thorball. “The science is interesting but it’s not relevant for the patient, only products are relevant. When science says we can cure something and there is no product, what does the patient do?”

Unlike other stem cell methodologies, Ahlfors is focusing on an “autologous” process, which ensures that the cells are not rejected by the patient, unlike experiments using cells harvested from other sources.

One barrier to growth is that different governments have varying laws on whether an individual can have their own cells harvested. This is not currently possible in the UK or US.

“It seems ridiculous to tell people that they cannot have their own cells, but the regulations are very different depending where you are in the world,” says Thorball.

Other companies have allegedly made headway in stem cell research. Last year, the BBC’s Panorama programme followed the treatment of one paralysed man in Poland, who was filmed walking again for the first time after his accident. Thorball warned against taking claims made by stem cell researchers that are based on a single selected patient.

“In that case, the spinal cord was not severed, just damaged,” says Thorball. “He already had some ability, so the regrowth is a matter of discussion.”

Ophiuchus will work hard towards rolling out treatments in private clinics within two years. The company is aiming to create a mass-market product within a decade. Investor Richard said: “All the insurance companies will begin covering the treatment because even though it will be expensive, it will be much less expensive than treating people for the rest of their lives for a disease, or keeping them in a wheelchair.”




In our post in September 2013 we have announced possibility for further development and possible human trial for this drug.
Spinalon will affect walking pattern generator in spinal cord on the way to produce short outburst of involuntary walking motion that will last for 30 – 40 minutes.
This drug have no ability to recover or reconnect damaged nerves and patients (chronic para and quadriplegic Spinal Cord Injuries) will be able to walk just @ controlled treadmill environment.

More details about this trial in Press Release and
Blog Spinal Cord Injuries Research & Advocacy.

Brain Repair in the Pill

For the first time, researchers have used a cocktail of small molecules to transform human brain cells, called astroglial cells, into functioning neurons for brain repair. The new technology opens the door to the future development of drugs that patients could take as pills to regenerate neurons and to restore brain functions lost after traumatic injuries, stroke, or diseases such as Alzheimer’s. Previous research, such as conventional stem cell therapy, requires brain surgery and therefore is much more invasive and prone to immune-system rejection and other problems. The research, led by Gong Chen, Professor of Biology and the Verne M. Willaman Chair in Life Sciences at Penn State University, will be published online in the journal Cell Stem Cell on Oct. 15th, 2015.

My testing of New medication – 4-AP-3-MeOH

  This my own observation and it’s not based on any medical & scientific
basis, methods or guidelines. I would ask anyone to take caution and consult
doctor before trying to repeat any of my ideas.

Conclusion: Potassium channel blocker – 4-AP-3-MeOH – New signal enhancer medication – will increase ability of damaged or less functional nerves to conduct signals and can help with exercise, in functional recovery program and during the rehab for Incomplete Spinal Cord Injuries.
With medication 4-AP-3-MeOH (currently 2 x 0.5 mg daily) I am taking for the last 4 weeks,
I am actually improving my posture and my ability to walk in higher platform
walker with knee braces (time and distance).  Also, this medication is cause of increased
time and strength of pushing and frequency of good steps and time
of walking on treadmill with.suspended weight.

I have no side-effects so far and I am trying to keep “monitoring” and I will post any changes here.

Dosage is crucial. I got my capsules as 0.5 mg (as this compound is
10x stronger than  Ampyra) and I have started by one daily, increasing
to 2, 3 and 4 daily slowly and decreasing slowly back to 2 daily within 2 weeks period.
I didn’t notice any side effects except slightly buzzing in my head when I had 4 x 0.5 mg**
(**which is, anyway hard to confirm with my chronic tinnitus 🙂 .
During this period and all time taking 4-AP-3-MeOH I did not take an alcohol or any other drug except aspirin.

I have very significant firmness in my legs, in my core, my non working fingers flickering.
My spasms didn’t increased with 4-AP-3-MeOH as with Ampyra in May this year,
rather there is less spasms, but when spasms happens they are stronger.
Somehow, my overall energy increased. Ability to voluntary and functionally move limbs just slightly increased.

Now I am planing to stop taking this cat – “MeeeOH” as I call it, for
a week or 2 to cleanse little bit, get some wine and see how this period without drug
will reflect on me and I am planning to start to take another round after that and I
will try to increase my exercise level along with dosage, to maybe 5 x 0.5 mg in time of heavy workouts. I am pretty sure that gradually increasing dosage in time of heavy exercise program time and than gradually decreasing dosage for less activity period is safe to do.

According to all research and data comparison, only benefits, old incomplete SCI
patients would get from long (6 months at least) and extremely hard walking exercise program.
If accompanies this exercise program with medication that increase signal strength (as 4-AP-3-MeOH) and possibly even use a system as Parastep (Functional Electric Stimulation & suspended weight walk), chances for good outcome would be much higher.


This compound drug is available from several places and I got 100
capsules for US $ 100 from UK compound pharmacy mod4all.com .
Shelf life is apparently much longer (18-24 months) than 4AP.


Since my SCI Injury (C-6 Incomplete) 12 years ago in waves of Virginia
Beach, I am trying to put together extremely complex and by medicine science
impossible-to-solve puzzle with picture of myself walking again.
After being ditched by Canadian Health care system that would rather promote dependability and assists business of wheelchair & various equipment & supplies, health care system that would  never prescribe more than 12 physio therapies through 1 year (1 per month) for “chronic” spinal cord injuries, I have found myself paying for my own physio-therapies overseas, in my native Bosnia & Herzegovina in Rehab center in Fojnica, where I had recovered within 3 months to be able to walk in parallel bars with knee braces only.
Unfortunately I was able to travel to that rehab only twice (by 3 months) within 2 years
after my injury. With every return to Canada and after longer periods
without quality & quantity exercises, I lost all achieved improvements.
I knew that any improvement with my condition will be very hard to
achieve but I had no Idea will be so easy to lose it.
Only way to get lasting effect will be to exercise long & hard enough to put your mind and body  over the threshold that will make yourself (body) going into mode of self recovery.
Only some very small percent of people figure out how to do it and did it.
As every incomplete injury is different there is no template, manual how to do it.
Each and every one of us, prisoners of our own broken body need to
find our own way, and everyone’s recovery and exercise program should
be custom and different.
However, some things works for All Incomplete Spinal Cord Injuries!
Program based on controlled and focused exercises, specially standing and walking (with
necessary help of others or help of needed devices) as often as possible over some longer period of time (at least 6 months) would bring certain improvement to any incomplete SCI person!
Some people recover more, some less  – depend of several factors.


With incomplete SCI you can often find that only one smaller part of
the spinal cord has been damaged, contused, bruised with only some
nerves physically cut and the most of nerves intact.
Due to immediate “short circuit” reaction  within spinal cord in moment or immediately after the
injury patient will go into “spinal shock” state, where the most neuro-signals below injury level are cut off. Even their intact nerves stop conducting proper signals.
In some cases person get lucky and after some time spinal shock effect
diminishes over the time and some of the functions get returned.
What is real mechanism of spinal shock and how its working is still great mystery.
Now, some of non-cut nerves that refuse to come back into conduction
signal mode are actually overstretched or contused / compressed
and their axons (center part of nerve) are intact but their own
insulation myelin sheet are jeopardized, so signal transfer has been interrupted.
That interruption could cause very weak, sporadic signal that for
effect has limited or weak ability of certain muscles to contract /
move or they can cause sporadic or more constant spasm’s.
Thanks to potassium channel blockers that acting as artificial nerve
insulators (Pyridine’s group (4-AP) ),
patient can get extra help in effort to re-establish neurological pathways.
Problem with potassium channel blockers is they can cause side effects.
Some side effects can be serious as epileptic seizures and due to
highly unique “configuration” of every injury, it is almost impossible
to establish universal dosage. That’s why each patient who is taking potassium
channel blockers need to go through careful ramping process to find
out what dosage will work for him / her.
There are several pyridine based blockers – first, the oldest one is
generic 4-AP drug know for few decades, made by compound pharmacies and
used by lot of people with more or less success.
There is also slow release version of the same drug approved about 5
years ago known as Ampyra in USA (Fampyra – Canadian version).
This drug is very expensive ($ 600 – $ 900 monthly dose) for non
insured people and it is approved for MS patients but never officially
approved for Spinal Cord injured patients exactly from the same reason of inability to
establish universal dosage.
Third generation of this drug is 4-AP-3-MeOH, 10 X stronger and with
less side effects than predecessors.
This drug came from Lab of Dr. Shi (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019253/ )
and it was tested on animals only – never being tested on humans.


Yes, I feel as a Lab Rat…testing alone something that was tested on animals only.
Well,  I have already tried, by my Spinal Cord doctor prescribed, similar medcation
“Ampyra” in May of this year when I visit again Rehab center in Bosnia
and after few weeks I didn’t notice almost any serious side effects taking
2 x 10 mg recommended dose of this medication..
I was there in SCI Rehab Clinic for 45 days and once I had
finished my training session in rehab center in Bosnia I have stop taking
Ampyra. With Ampyra, major differences caused with this medication were
overall 200% greater stiffness of my legs and some stronger spasm’s.
In that Rehab time I have focused more on core and lower back
exercises and not on walking.

Let me explain something – about use of “walking” term here:
There are 2 type of “walking” I perform – walking with knee braces in
tall platform walker with belt behind me and there is also
suspended weight type of walking on treadmill with help of my feet positioning.
I have platform walker in my home and usually walk every morning 30
min or less after stretching exercises.
This walk I call “Frankenstein” walk with knee braces that lock my
knees for standing and stiffing my legs bearing full body weight.
Second type is “more natural” , knee bending walk and I am able to do
it @ MacWheelers gym in Hamilton Ontario, thanks to the staff & students
of McMaster University /  Kinesiology / Volunteers.
Twice per week by 30 – 35 minutes I am walking with half of my weight
suspended over the treadmill and 2 students are helping me with moving
and positioning my feet.
With 4-AP-3-MeOH (2 x 0.5 mg daily) that i am taking for the last 4
weeks, I am actually improved and hope to keep improving by
lowering suspended weight (from 63 to 50 kilos just recently) and
increasing frequency of good steps.

Again, I will keep “monitoring” and I will post any changes here.
Your comments are welcomed!

Zel Komadina
Miracle of Walk

Non-invasive technique to transplant cells into the nervous system


Dr. Sekiya Dr. Sekiya A research team led by Dr Testuji Sekiya at Kyoto University’s Graduate School of Medicine has discovered a new, non-invasive technique to transplant cells into the nervous system. They show that the “glial scar”, commonly thought to be an obstacle to regeneration, can provide critical cues to the integration of donor cells.

Patients suffering from spinal cord injury and from neurodegenerative disorders such as Parkinson’s disease and amyotrophic lateral sclerosis have high hopes for cell transplantation therapy. However, survival and integration of transplanted cells is often poor and thought to be inhibited by scar tissue that is produced by non-neuronal supporting cells called glial cells. Thus the glial scar is believed to be a major barrier to successful cell transplantation to the nervous system. The current practice is to deliver cells directly into nerve tissue through a fine tube, the idea being to place cells as close as…

View original post 554 more words