Who is the cure for?

[Christopher Paddon]

Wise, I am putting you on the spot not for the first time. You are always so much more optimistic than others in the medical profession about sci cure but then you know the topic better than almost anyone else.

If, for argument's sake, being wildly optimistic the first clinical trials in ChinaSCINet actually yield a treatment that gets people up and walking is it only the comparatively young that will benefit?

I'm 53 now and been paraplegic for 29 years - has my time run out? I think it's why some of the younger newer injuries accuse the older ones of not supporting a cure. Well, a lot of the older guys and girls feel it is too late for them - but is that wrong?


Thanks

[rjg]

Good question. As a c6-7 quad who's 29 and nearly 12 years post, you and I have more in common than I'd care to admit. I tend to think that 3 years is the same as 30 if spasms are present, but only Dr. Young is qualified to say for sure.

[susanrotchy]

What is a Cure

It depends on what you think a cure is? I have been advocating for a cure for years when I first was injured a cure was walking if you ask me today it is not about walking. Having your bowels and bladder function and having feeling being able to transfer is a cure today for me. But I would never turn down walking or stop fighting for Paralysis because it could benefit my child that is not injured or others. It is the secondary conditions that trap us in our bodies and take over our lives. No more Pressure sores, UTI’s and broken bones that don’t heal is my cure 15 years later.

[ineedmyelin]

Christopher Paddon,

GREAT question! i too feel like my window of opportunity is starting to close. i'm a walking incomplete quad 41 yrs old and 21 yrs post injury. i'm finding it harder and harder everyday to deal with this life. i have decent muscle throughout my legs and arms etc but both my knees and shoulders feel like there shot. i cant sleep at night because the right side of my back spasms and tightens all night long, my doctor says its because of my c4-c5 fusion causing strain on c6-c7 vertabraes. l continue to think that i would benefit greatly from remylination therapy.

God speed to you Dr Young cause a lot of us are starting to lose the edge we once had.

[gjnl]

I think the "cure" for those of us who are long term injured (I am C6/7 complete post 29 years) may entail more pain than we can possibly imagine, even though many of us suffer greatly from various forms of pain now. Imagine flipping the "cure switch" (I know that is trite and over simplified), turning on all of those neurons and nerve fibers that haven't been communicating with our brains or the pain involved in enervating long dormant muscles. Maybe the "cure" for those of us long injured may be worse than the "disease." I'm am sure researchers have this in mind as they put more pieces of the puzzle together and develop criteria for offering the cure, when it comes, to those of us with spinal cord injuries.

All the best,
GJ

[ineedmyelin]

Wise, I am putting you on the spot not for the first time. You are always so much more optimistic than others in the medical profession about sci cure but then you know the topic better than almost anyone else.

If, for argument's sake, being wildly optimistic the first clinical trials in ChinaSCINet actually yield a treatment that gets people up and walking is it only the comparatively young that will benefit?

I'm 53 now and been paraplegic for 29 years - has my time run out? I think it's why some of the younger newer injuries accuse the older ones of not supporting a cure. Well, a lot of the older guys and girls feel it is too late for them - but is that wrong?


Thanks

bumpity bump

[Dale]

Me at 73 (this month) and 5 years post, T12 incomplete. I'm being optimistic. Hopefully
the cure will come before I check out.

[khmorgan]

My definition of a cure

My definition of a cure is to restore enough of your spinal column that you are only limited in your recovery by how much you can restore your bones and muscles.

I'm a C5/C6 incomplete and 45 years post. I know full well that I'll never walk again, and you know, I don't care. Just give me control of my muscles, get rid of the neuropathic pain, and make it my responsibility to do the rest.

[TMAZ]

So what if the cure was here already meaning that the scientists can measure functionality but cannot measure the subjective experience. Would you take the cure and make it a crap shoot to see how it affects your pain levels, overall wellbeing, and more importantly your bladder,sexual, and bowel functions? As the years go by I often wonder if I want anything else. I am uncertain of the future already but my pain is managed and I do walk but also have other side effects of SCI that I of course do not want. I guess my point is when would be the right time to get treatmnt if it was available?

[Wise Young]

Wise, I am putting you on the spot not for the first time. You are always so much more optimistic than others in the medical profession about sci cure but then you know the topic better than almost anyone else.

If, for argument's sake, being wildly optimistic the first clinical trials in ChinaSCINet actually yield a treatment that gets people up and walking is it only the comparatively young that will benefit?

I'm 53 now and been paraplegic for 29 years - has my time run out? I think it's why some of the younger newer injuries accuse the older ones of not supporting a cure. Well, a lot of the older guys and girls feel it is too late for them - but is that wrong?


Thanks

Christopher,

Good question. As you may know, our phase 2 trial is looking at patients between ages 18 and 60 in Hong Kong and China. Depending on the safety of the therapy seen in the trials now, we are considering increasing that range to 18-64 years. By the way, this does not mean that I don't think the treatment will be effective in even older patients. That would need to be a subject of further studies in the coming trials.

So, no, I don't consider you over the hill at age 53 and 29 years after injury. I believe that the spinal cord is continuing to try to regrow and recover 20, 30, 40, or even 50 years after injury. In fact, it is possible that older people might respond more to regenerative therapy than younger ones. That is because the growth factor levels and endogenous stem cell activities of older people are less so that adding growth factors and younger stem cells will have greater effects.

That is the one advantage of umbilical cord blood stem cells over autologous bone marrow stem cells. Umbilical cord blood cells are likely to work equally in young and old people, as opposed to autologous bone marrow cells which many investigators have shown to have fewer and less active stem cells at ages above 50.

Of course, aging bones and joints, as well as atrophied muscles, may not respond as alacritously. On the other hand, I am not sure that age really makes that much of a difference in terms of bones and muscles. After all, at age 61, if I were to take up weight-lifting as a hobby, I can build both my muscles and bones. It will take a long time, to be sure.

The body doesn't spend the energy maintaining structures that they don't use. So, an astronaut will suffer over 50% calcium loss from his or her bones after several months in microgravity. It takes years to restore the calcium levels and bone strength. I think the same thing is true for bones, joints, and muscles of people with spinal cord injury. I don't think that there is a cut off.

Finally, what about the nervous system? Do axons grow slower (just like hair grows slower) with age? Some scientist seem to think that aging neurons, muscles, and cells are less responsive to neurotrophins [1]. Rose, et al. [2] grew retinas from monkeys of different ages to see if aging monkey retinal ganglion cells have different capacity for growth. They found "Vigorous regeneration of axons occurred from identifiable morphological types of RGCs throughout all stages of life, although the numbers of axons decreased with age."

A lot of the data suggesting that regeneration declines with age compared embryonic development with young animals and not necessarily young versus aged animals. Expression of certain genes may play a role in determining the response of neurons to stimuli to regenerate [3]. Thus, even if aging does slow regeneration, it may be possible to regenerate despite aging by turning on the appropriate genes. Let's cross that bridge when we come to it.

Wise.

References cited

1. Kovacic U, Sketelj J and Bajrovic FF (2009). Chapter 26: Age-related differences in the reinnervation after peripheral nerve injury. Int Rev Neurobiol 87: 465-82. Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia. Numerous and extensive functional, structural, and biochemical changes characterize intact aged peripheral nervous system. Functional recovery after peripheral nerve injury depends on survival of injured neurons and functional reinnervation of target tissue by regeneration of injured axons and collateral sprouting of uninjured (intact) adjacent axons. The rate of axonal regeneration becomes slower and its extent (density and number of regenerating axons) decreases in aged animals. Aging also impairs terminal sprouting of regenerated axons and collateral sprouting of intact adjacent axons, thus further limiting target reinnervation and its functional recovery. Decreased survival of aged noninjured and injured neurons, limited intrinsic growth potential of neuron, alteration in its responsiveness to stimulatory or inhibitory environmental factors, and changes in the peripheral neural pathways and target tissues are possible reasons for impaired reinnervation after peripheral nerve injury in old age. The review of present data suggests that this impairment is mostly due to the age-related changes in the peripheral neural pathways and target tissues, and not due to the limited intrinsic growth capacity of neurons or their reduced responsiveness to trophic factors. Age-related alterations in the soluble target derived neurotrophic factors, like nerve growth factor, and nonsoluble extracellular matrix components of neural pathways, like laminin, might be important in this respect.
   
2. Rose K, Schroer U, Volk GF, Schlatt S, Konig S, Feigenspan A and Thanos S (2008). Axonal regeneration in the organotypically cultured monkey retina: biological aspects, dependence on substrates and age-related proteomic profiling. Restor Neurol Neurosci 26: 249-66. Department of Experimental Ophthalmology, University Eye Hospital Munster, Munster, Germany. Injury to the mature primate and subprimate optic nerve results in irreversible impairment and loss of vision, because the retinal ganglion cells (RGCs) fail to regenerate their cut axons within the optic nerve interior. This study was performed to examine whether aging monkey RGCs retain the ability to regenerate their axons in organ culture and whether axonal regeneration is associated with specific proteomic profile. Retinal stripes obtained from marmoset eyes (C. jacchus) were cultured between the day of birth and adult stages on different substrates like laminin-1, laminin-2, collagen, matrigel and poly-D-lysine. No neurotrophic factors were added to the medium. Axonal growth was monitored with microscopy and immunohistochemistry. Onset and rate of growth was examined with time-lapse videography. Vigorous regeneration of axons occurred from identifiable morphological types of RGCs throughout all stages of life, although the numbers of axons decreased with age. Axonal growth occurred virtually only on laminin-1. Growth correlated with re-expression of the laminin-1 receptor alpha6-integrin and sustained staining for GAP-43 as shown by immunohistochemistry and immunoblotting. At proteomic level, there is a maturation-dependent change in the protein immunostaining within the retina. When retinal slices of the same age were compared, regeneration-specific protein staining included calmodulin, fatty acid binding protein, alpha-crystallin, IFN-gamma, cyclin-dependent kinase inhibitor (p21), beta-hemoglobin, 60s-ribosomal protein, GAP-DH and ADP-ribosylation factor (ARF). To our knowledge these data are the first from subhuman animals to suggest that axonal regeneration of injured RGCs is correlated to expression of identifiable proteins within the retina.
   
3. Parikh P, Hao Y, Hosseinkhani M, Patil SB, Huntley GW, Tessier-Lavigne M and Zou H (2011). Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci U S A 108: E99-107. Fishberg Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. Axon growth potential is highest in young neurons but diminishes with age, thus becoming a significant obstacle to axonal regeneration after injury in maturity. The mechanism for the decline is incompletely understood, and no effective clinical treatment is available to rekindle innate growth capability. Here, we show that Smad1-dependent bone morphogenetic protein (BMP) signaling is developmentally regulated and governs axonal growth in dorsal root ganglion (DRG) neurons. Down-regulation of the pathway contributes to the age-related decline of the axon growth potential. Reactivating Smad1 selectively in adult DRG neurons results in sensory axon regeneration in a mouse model of spinal cord injury (SCI). Smad1 signaling can be effectively manipulated by an adeno-associated virus (AAV) vector encoding BMP4 delivered by a clinically applicable and minimally invasive technique, an approach devoid of unwanted abnormalities in mechanosensation or pain perception. Importantly, transected axons are able to regenerate even when the AAV treatment is delivered after SCI, thus mimicking a clinically relevant scenario. Together, our results identify a therapeutic target to promote axonal regeneration after SCI.
   
   

[#LHB#]

At almost 26 years old inject me and i will take my chances of breaking a leg to get better.

[christopher]

I think the "cure" for those of us who are long term injured (I am C6/7 complete post 29 years) may entail more pain than we can possibly imagine, even though many of us suffer greatly from various forms of pain now. Imagine flipping the "cure switch" (I know that is trite and over simplified), turning on all of those neurons and nerve fibers that haven't been communicating with our brains or the pain involved in enervating long dormant muscles. Maybe the "cure" for those of us long injured may be worse than the "disease." I'm am sure researchers have this in mind as they put more pieces of the puzzle together and develop criteria for offering the cure, when it comes, to those of us with spinal cord injuries.

All the best,
GJ

This is my greatest concern regarding a cure as well. At what cost would a cure benefit me? To walk again, to be able to pee on a tree would be great, but not at the cost of living in constant pain.

[Christopher Paddon]

Thanks Wise

I guess my next related question is how easily could the treatment be taught to other neurosurgeons and rehab teams?

The cure may be there in China/US/Europe but in all likelihood myself and others in New Zealand and other places couldn't afford to travel or be able to jump the queue.

Would you be able to simply fly to New Zealand and teach the Auckland neurosurgeons what to do? Or they simply get instruction over the internet? Or would they need to be comprehensively retrained? (which they may not bother to do)

[cajun]

If prospective cures come along, some will be brave enough or desperate enough to give it a try. It won't take long until at least the short-term effects are known. Of course, with the complexity of our universe, I'm betting that it still won't be an easy decision, lol. God isn't merciful, he's a comedian.

[Donnie]

Chris, You shouldnt worry about how to get a treatment until one of them is proven effective. Don't put the wagon before the horse...