Invited Speaker Sydney Spinal Symposium 2022

Chronic low back pain is one of the leading causes of adult disability globally. Currently there are no therapeutic options that target the common pathology of back pain; intervertebral disc degeneration. Intradiscal therapeutics aim to treat some aspects of the pathological disease process, by regenerating or assisting bio-physical characteristics of the intervertebral disc. We first found that mutation in GDF6 leads to the absence of disc in Klippel Feil Syndrome(1). Utilising the principle that ontogeny, or growth and development is replicated during healing of tissues, we demonstrated in three animal models (Sheep, Rabbit(3) and rats(2)) that the recombinant protein or rhGDF6 can regenerate(4) the injured disc and further, improve pain. We are now working towards starting early stage human trials. The talk will discuss the 25-year journey till now and outline the next 5 years.  

1. Tassabehji M, Fang ZM, Hilton EN, McGaughran J, Zhao Z, de Bock CE, Howard E, Malass M, Donnai D, Diwan A, Manson FD, Murrell D, and Clarke RA. Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. Hum Mutat. 2008; 29: 1017-1027.
2. Cui H, Zhang J, Li Z, Chen F, Cui H, Du X, Liu H, Wang J, Diwan AD, Zheng Z. Growth differentiation factor-6 attenuates inflammatory and pain-related factors and degenerated disc-induced pain behaviors in rat model. J Orthop Res. 2020 Jul 03. doi: 10.1002/jor.24793. Epub ahead of print. PMID: 32617997.
3. Miyazaki S, Diwan AD, Kato K, Cheng K, Bae WC, Sun Y, Yamada J, Muehleman C, Lenz ME, Inoue N, Sah RL, Kawakami M, Masuda K. ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model. Eur Spine J. 2018 Apr;27(4):739-751. doi: 10.1007/s00586-018-5488-1. Epub 2018 Feb 19. PubMed PMID: 29460012; PubMed Central PMCID: PMC5874179.
4. Hodgkinson, T.; Gilbert, H.T.J.; Pandya, T.; Diwan, A.D.; Hoyland, J.A.; Richardson, S.M. Regenerative Response of Degenerate Human Nucleus Pulposus Cells to GDF6 Stimulation. Int. J. Mol. Sci. 2020, 21, 7143.