I apologize for the long time in between posts. I was away dealing with a little something called my oral boards. The board certification process in neurosurgery typically takes several years as the surgeon has to accrue case data for review by members of the American Board of Neurological Surgeons (ABNS). This long and tedious process begins with a written exam at the end of residency and culminates with a 3-hour oral exam several years into practice. During this oral exam you are presented case after case to see how you manage typical situations in the O.R., including complications. I just received word that I passed and am now officially a “board-certified” neurosurgeon. Believe me, I am thrilled that this hurdle is behind me.
I thought I’d take a break from our march through the various topics of cervical pathology and talk about something that I came across in the mass media not too long ago. Patients frequently ask me “well Doc, isn’t there something you can inject into my disc to make me all better?” The short answer is no, not yet, but there may be soon. In the next two posts we’ll discuss the basic science behind restorative therapies for degenerative conditions of the spine. In the first part we’ll discuss a recently developed injection therapy that has been shown to block inflammatory mediators that may be important in degenerative disc disease (DDD.) In the next post we’ll discuss stem cell therapies for DDD. I’ll refer to these topics collectively as the biologics of DDD.
On the cover of March 2014 issue of Men’s Journal there is a header that reads “NO SURGERY REQUIRED-High Tech Treatments for Knees & Backs.” (Note: I will NOT use this as an opportunity to vent about how sick and tired I am of the mass media’s assault on the efficacy of spinal surgery and the integrity of spinal surgeons.) The article describes a process in which a patient’s blood is incubated and injected (as autologous conditioned serum or ACS) into an inflamed joint or spine. This process, patented by a German orthopedic surgeon, Dr. Peter Wehling, as Regenokine, is heralded as a “painless” way for patients suffering from the chronic pain of chronic arthritis to avoid surgery (which as described so eloquently in the article “sucks in general.”) Now, I am always initially suspicious of a treatment that a) hasn’t been evaluated by the FDA, b) is a proprietary treatment method that costs as much as $10,000 cash up front (ACS isn’t covered by insurance) and c) is touted in the mass media, rather than in neurosurgical journals, as a miracle cure for a long-standing affliction. That said, the science behind treatments like ACS is sound.
In order to understand how therapies like ACS combat DDD you must first understand the structure of an intervertebral disc (IVD). The IVD is comprised of an inner nucleus pulposus (gel-like in consistency due to its combination of proteoglycans and type II collagen) and the outer annulus fibrosus (strong and fibrous like kevlar due to its type I collagen.) These inner layers are held together by cartilaginous endplates above and below (one patient recently told me that this looked like an ice cream sandwich to her; see figure 1.) Various populations of cells within the IVD maintain the health of these structural components through the secretion of a perfectly balanced concoction of cytokines and growth factors. At some point in adult life this delicate balance is disrupted in favor of so-called pro-inflammatory cytokines that promote the breakdown of the proteoglycans and collagens within the IVD. Eventually the gel-like nucleus pulposus is replaced by firm, fibrous scar tissue (not a good shock absorber like the normal nucleus pulposus) and the annulus fibrosus tears and fails under the increased load. This is DDD in a nutshell.
Figure 1: Intervertebral disc with the inner gelatinous nucleus pulposus and outer annulus fibrosus. (Source: http://www.porcpotlas.hu/en/porckorong.html)
One of the pro-inflammatory cytokines that has been well-studied is interleukin-1 (IL-1). Lab studies of human IVD cells show that IL-1 will stimulate the production of chemicals (matrix metalloproteinases if you’re interested) that break down components of the disc and will also turn off the genes that produce collagens and proteoglycans. So if you’re a fan of disc health IL-1 is the bad guy. Your body will keep IL-1 in check by concurrently producing a chemical that competes with IL-1 at its binding sites. Let’s call this IL-1ra for IL-1 receptor antagonist. In a degenerated IVD, as well as in other degenerated collagen-based tissues like knees and shoulders, IL-1 levels skyrocket while IL-1ra levels plummet so inflammation runs unchecked. This is where ACS comes in. In ACS, a patient’s venous blood is drawn and incubated in such a way that concentrates the levels of IL-1ra to levels that are 150 times normal levels (see figure 2). The resulting serum is injected into the inflamed joints or into the spines of patients where IL-1ra combats the effects of IL-1 thereby halting inflammation and degeneration to relieve pain.
Figure 2: Schematic of the ACS treatment (source: Wehling P, Moser C, Frisbie D, McIlwraith CW, Kawcak CE, Krauspe R, et al.: Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy. BioDrugs 21:323–32, 2007.)
Another therapy, platelet-rich plasma (PRP), also uses the patient’s own blood to combat degeneration of connective tissue. PRP is thought to act by increasing the amount of local growth factors available to stimulate native cells to repair the degenerated tissue in the disc. In summary, both ACS and PRP tip the balance in favor of repair and regeneration of the connective tissue of the degenerated disc.
The data in support of the ACS treatment the strongest for orthopedic conditions such as tennis elbow and knee arthritis. The data supporting the use of ACS in degenerative spinal conditions, however, is less clear. In one double-blinded study (Becker et al, 2007) there was minimal increased benefit of ACS when compared to steroids for use in spinal epidural injections for radiculopathy (pinched nerve.) I think that more randomized trials are needed to prove that ACS is superior to current treatments.
While early data on these new biologic treatments is still mixed, the prospect of regenerative treatments for DDD and arthritis is very exciting. Surely we’re just beginning to understand the importance of these interdependent chemical signals and how they relate to DDD. I can’t help to think that someday, after treatments like these become mainstream, we’ll look back and wonder in astonishment about how we ever thought that a lumbar fusion, currently the gold standard for treatment of DDD, was ever considered a standard treatment at all!
Thanks for following along. I know it was a complicated post!
J. Alex Thomas, M.D.
Becker C, Heidersdorf S, Drewlo S, de Rodriguez SZ, Krämer J, Willburger RE: Efficacy of epidural perineural injections with autologous conditioned serum for lumbar radicular compression: an investigator-initiated, prospective, double-blind, reference-controlled study. Spine (Phila Pa 1976) 32:1803–8, 2007.
Le Maitre CL, Freemont AJ, Hoyland JA: The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther 7:R732–45, 2005.
Masuda K, An HS: Prevention of disc degeneration with growth factors. Eur Spine J 15 Suppl 3:S422–32, 2006.
Wehling P, Moser C, Frisbie D, McIlwraith CW, Kawcak CE, Krauspe R, et al.: Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy. BioDrugs 21:323–32, 2007.