NTG-101: A Novel Molecular Therapy that Halts the Progression of Degenerative Disc Disease.

The tremendous cost, pain and disability associated with degenerative disc disease (DDD) makes the development of a biological agent that can mitigate the course of DDD, a critical unmet need. We have identified and reported that a single injection of a combination of recombinant human (rh) Transforming growth factor beta 1 (TGF-ß1) and Connective tissue growth factor (CTGF) proteins into the injured intervertebral disc (IVD) nucleus pulposus (NP) can mediate DDD in a pre-clinical rodent model. In this study, we developed and evaluated the efficacy of a novel molecular therapy (NTG-101) containing rhTGF-ß1 and rhCTGF proteins suspended in an excipient solution using in vivo models of DDD including rat-tail and chondrodystrophic (CD) canines. Needle puncture injury in CD-canine NPs resulted in loss of hydration, disc height and showed radiographic evidence of DDD like humans. However, NTG-101-injected IVDs maintained disc height and demonstrated retention of viscoelastic properties as compared to IVDs injected with phosphate buffer saline (PBS, 1X, pH = 7.2). In addition, a single intra-discal injection of NTG-101 into the injured IVD-NPs resulted in sustained expression of healthy extra-cellular matrix (ECM) proteins (aggrecan, collagen 2A1) and reduced expression of inflammation associated proteins and molecules (IL-1ß, IL-6, IL-8, MMP-13, Cox-2 and PGE2) as compared to vehicle controls. In conclusion, we demonstrated that a single intra-discal injection of the novel formulation, NTG-101 confers a robust anti-inflammatory, anti-catabolic and pro-anabolic effects in pre-clinical models of DDD thereby restoring homeostasis. These findings suggest the therapeutic potential of NTG-101 for clinical use.

Biochemical injection treatment for discogenic low back pain: a pilot study.

BACKGROUND CONTEXT: Biochemical treatment options including attempts at intervertebral disc restoration are desirable for the physiologic treatment of degenerative disc disease. PURPOSE: This was a pilot study to test the potential effectiveness of intradiscal injection therapy using agents known to induce proteoglycan synthesis in the treatment of intervertebral disc disease. STUDY DESIGN: Prospective, within subject, experimental design was applied in the study. PATIENT SAMPLE: Thirty patients, average age 46.5 years, with chronic intractable low back pain of 8.5 years average duration, took part in the study. All patients had lumbar discography with reproduction of pain. OUTCOME MEASURES: Pretreatment Roland-Morris disability scores and visual analogue scores were compared with 1-year follow-up posttest values of these scores. METHODS: Lumbar intervertebral discs were injected with a solution of glucosamine and chondroitin sulfate combined with hypertonic dextrose and dimethlysulfoxide (DMSO). Assessment of pain and disability was completed before treatment and an average of 12 months after the last treatment. RESULTS: Posttreatment Roland-Morris scores for the entire group of 30 patients of 6.4+/-.994 were significantly (p<.001) lower than pretreatment scores of 12.0+/-.92 (mean+/-SE). The posttreatment visual analogue scores of 3.00+/-.44 were also significantly less than the pretreatment of 6.11+/-.33 (mean+/-SE). Although the results were statistically significant for the 30 patients as a whole, 17 of the 30 patients (57%) improved markedly with an average of 72% improvement in disability scores and 76% in visual analogue scores. The other 13 patients (43%) had little or no improvement. Patients who did poorly included those with failed spinal surgery, spinal stenosis and long-term disability. There were no complications or serious side effects, although postinjection pain was moderate to severe for 48 to 72 hours and required epidural steroids in five cases. CONCLUSIONS: The results of this pilot study suggest that intradiscal injection therapy with glucosamine, chondroitin sulfate, hypertonic dextrose and DMSO warrants further evaluation with randomized controlled trials.