Two preclinical studies of IDCT, an allogenic (donor-derived), non-invasive cell therapy for the treatment of degenerative disc disease (DDD), demonstrate that proprietary discogenic cells, the active ingredient of IDCT, are safe and non-tumor forming. DiscGenics, a clinical stage regenerative medicine company developing cell therapies for patients with mild to moderate DDD, announced these results at the Orthopaedic Research Society (ORS) 2018 Annual Meeting (10—13 March, New Orleans, USA).
Discogenic cells are highly specialised therapeutic progenitor cells derived from donated intervertebral disc tissue and engineered to address the complex environment of the degenerated disc. For the purposes of these studies and for the company’s Phase I/II clinical trial of IDCT, the discogenic cells are combined with a viscous delivery vehicle (saline or sodium hyaluronate) prior to injection.
The two preclinical studies, which evaluated the safety and bioactivity of discogenic cells implanted in subcutaneous pouches of athymic mice and rabbit disc models, respectively, demonstrated that discogenic cells have the ability to generate intervertebral-like tissue.
For example, in the mouse study, male and female athymic mice were injected with either a supra-physiological dose of discogenic cells (10 million per 0.2 mL) with sodium hyaluronate and cryopreservatives, a cell-free injection of vehicle alone, or 10 million HeLa cells in EMEM into a subscapular pouch (n=10 animals/group). The mice were then observed daily for body weight, morbidity, mortality, and for the presence of tumors. After four months, the animals were euthanised and a gross necropsy was performed.
In four of 10 animals that received discogenic cells and vehicle, regions of cartilaginous, disc-like tissue were identified. These masses were small, encapsulated, and contained well-developed, non-neoplastic cartilage, fibrocartilage and dense fibrous connective tissue containing human discogenic cells. Proliferation was present at low levels. The cartilaginous matrix produced by discogenic cells and vehicle consisted of proteoglycan mixed with collagen fibers of varying sizes. This evidences that the discogenic cells generate intervertebral-like tissue in some instances, and thus have a regenerative capacity.
Both studies also resulted in disc height improvement and normalisation of tissue architecture.
Tissues and organs evaluated in animals treated with cells and vehicle did not contain neoplasms or distal metastases, consistent with a non-tumorigenic phenotype. When evaluating the animals that were treated with vehicle, no patterns of histologic findings were noted. In contrast, all animals that received the positive control (HeLa cells) developed carcinomas at the injection site, consistent with a tumorigenic profile.
Currently, IDCT is an investigational product that is under development by DiscGenics and has not been approved by the FDA or any other regulatory agency for human use.
Results from these studies support DiscGenics’ recently initiated US clinical trial of IDCT. The prospective, randomised, double-blinded, vehicle and placebo-controlled study will evaluate the cell therapy’s safety and preliminary efficacy in subjects with single-level, symptomatic lumbar DDD, a major cause of chronic low back pain. The estimated primary completion date is April 2020, and the estimated study completion date is April 2021.