Introduction

Lactic acid stimulates collagen deposition in the nucleus pulposus (NP) which increases flexural rigidity of the motion segment. Based on this observation, and on safety data from a phase 1b trial, STA363 (final formulation of lactic acid mixed with iohexol) is currently evaluated in a phase 2b study on patients with degenerative disc disease (DDD). Literature data show that both low pH and lactate reduce the levels of proteoglycans of the NP. It is therefore hypothesized that prior to establishment of fibrosis, STA363 has a chemonucleolytic effect and consequently, it may be used to treat radiculopathy caused by lumbar disc herniation. We therefore re-analyzed MRI data from a previous study on DDD patients to determine whether STA363 may act as a chemonucleolytic as indicated by disc height/volume reduction and dehydration of the NP.

Methods

In a phase 1b study on DDD patients, placebo (n=6) or STA363 (lactic acid at 45, 90 and 180 mg/disc, n=3 in each group) was injected into 1 or 2 lumbar discs (L3/4-L5/S1) of Pfirrmann grade 3, and disc height and width indices (disc height/width relative to the height of the cranial vertebra) were calculated. Intensity was evaluated by comparing MR images before and after injection. All measures were taken 12 months after treatment.

Results

Data from the patients treated with the lowest dose were not analyzed due to early withdrawal of one patient and the fact that only one disc/patient was injected in the two other patients. While disc height decreased by 5% in the placebo group, the decrease was 15% and 20% in the 90 and 180 mg groups, respectively (Table 1). Disc width did not change significantly. There was a consistent loss of intensity of NP in the two dose groups.

Discussion

Chemonucleolytics such as chymopapain and condoliase act by degrading water-binding glycosaminoglycans (GAGs) leading to dehydration, loss of disc height and volume which induces a drop in pressure. The decrease in disc pressure will be mirrored in the herniation as long as it communicates with the NP, causing it to shrink. The present work suggests that STA363 shares these fundamental properties of established chemonucleolytics. Since disc height but not width was reduced, disc volume must have decreased, consistent with water loss. Dehydration as reflected by T2-weighted MRI was also noted. In summary, STA363 may have a therapeutic utility in patients suffering from radiculopathy caused by lumbar disc herniation.

Table 1

*p<0.05; **p<0.01, Student’s paired t test