Ascentx Medical

S125 for Degenerative Disk Disease (DDD)

Degenerative Disc Disease

Degenerative Disc Disease (DDD) is thought to be the first step in degenerative spinal changes(18) and is considered to be one of the causes of several symptoms including lower back and neck pain.

The prevalence of DDD over the entire spine was found to be 71% in men and 77% in women aged <50 years, and >90% in both men and women aged >50 years. The prevalence of an intervertebral space with DD was highest at C5/6, T6/7, and L4/5. Age and obesity were associated with the presence of DDD in all regions. Low back pain was associated with the presence of DDD in the lumbar region.(19-22)

MRI image of normal, degenerated, and herniated disc

Several reports have found that DDD was a source of low back pain (discogenic pain)(18-21), and it is our belief that injection of polymethylmethacrylate (PMMA) microspheres carried in collagen into the center (nucleus pulposus) of a degenerated spinal disc may slow down DDD progression and provide pain relief via low-risk, least-invasive and cost-effective outpatient procedure.

Intervertebral Disc Injection

The nucleus pulposus is the soft center of the intervertebral disc and is contained by a strong fibrous tissue cover known as the annulus fibrosus (interwoven collagen fibers). The gel-like nucleus pulposus is responsible for shock absorption and motion of the spine. In young people it consists mostly of water and proteoglycans (similar to a small water balloon), yet as we get older, the disc, and especially the nucleus pulposus, dry out. This dehydration results in a significant loss of disc height, and by age 60 to 70, the disc is composed entirely of fibers, and the shock absorption for the spine is for the most part lost. As aging discs lose fluid and elasticity over time, they are more susceptible to compression and become thinner where even painful bone-on-bone contact may occur and the probability of spinal nerve impingement and back pain increases.

Degenerated Disc. NP=Nucleus Pulposus, IA=Inner Annulus, OA=Outer Annulus of L4/L5 lumbar disc

Based on pre-clinical testing in a sheep pilot study(23,24), where the original ArteFill® PMMA/collagen formulation was injected percutaneously into lumbar sheep spinal disc nuclei to treat annular injury, we believe that S125 PMMA/collagen injections hold promise for treating degenerative disc disease (DDD) through re-hydration of the nucleus, sealing of annular tears that can lead to nuclear prolapse, maintenance of normal disc cytoarchitecture, maintenance of disc height and improvement of elasticity (as opposed to a destructive process, where part or all of the disc is removed), as well as re-establishment of the nucleus’ shock absorbing function.

Previous animal study results revealed maintenance of the microspheres without migration to outer or inner annulus and early encapsulation of the injected material within the first 6 weeks.(23,24)

Healing of the annular defect occurred with formation of new collagen and without intense inflammatory response. Control discs revealed progressive degenerative changes in the annulus surrounding the created defect. No adverse events were noted in the treatment group.(23,24)

PMMA microsphere/collagen injections in sheep disc annular injury model

Despite the fact that our focus with S125 lies on the treatment of degenerated discs (which are composed of collagen, elastin, water and proteoglycans(22)), and not the bony vertebrae, the use of PMMA bone cement in the treatment of spinal fractures has a long history, including vertebroplasty and kyphoplasty. Both procedures have been widely used to treat painful, osteoporosis-related vertebral compression fractures in the spinal column. During both procedures, liquid PMMA bone cement is injected into fractured vertebrae, either via imaging guidance (vertebroplasty), or via insertion of a high-pressure balloon to first create a space and then fill it with cement (balloon kyphoplasty by KYPHON/Medtronic). Following such minimal-invasive “internal cast” procedures, about 75% of patients have shown to regain lost mobility and become more active:

Vertebroplasty (top) & Balloon Kyphoplasty (bottom) procedures via liquid PMMA injections

It is our goal, through continued research & development efforts, to further enhance biomaterial properties of S125 and clinically develop the ideal injectable spinal disc repair/sealant material for this potentially game-changing, least-invasive injection treatment for degenerative disc disease (DDD).