Innovative Genoceuticals in Human Gene Therapy Solutions: Challenges and Safe Clinical Trials of Orphan Gene Therapy Products

Abstract: The success of gene therapy attempts is controversial and inconclusive. Currently, it is popular among the public, the scientific community, and manufacturers of Gene Therapy Medical Products. In the absence of any remedy or treatment options available for untreatable inborn metabolic orphan or genetic diseases, cancer, or brain diseases, gene therapy treatment by genoceuticals and T-cells for gene editing and recovery remains the preferred choice as the last hope. A new concept of “Genoceutical Gene Therapy” by using orphan ‘nucleic acid-based therapy’ aims to introduce scientific principles of treating acquired tissue damage and rare diseases. These Orphan Genoceuticals provide new scope for the ‘genodrug’ development and evaluation of genoceuticals and gene products for ideal ‘gene therapy’ use in humans with marketing authorization application (MAA). This perspective study focuses on the quality control, safety, and efficacy requirements of using ‘nucleic acid-based and human cell-based new gene therapy’ genoceutical products to set scientific advice on genoceutical-based ‘orphan genodrug’ design for clinical trials as per Western and European guidelines. The ethical Western FDA and European EMA guidelines suggest stringent legal and technical requirements on genoceutical medical products or orphan genodrug use for other countries to frame their own guidelines. The introduction section proposes less-- known ‘orphan drug-like’ properties of modified RNA/DNA, human cell origin gene therapy medical products, and their transgene products. The clinical trial section explores the genoceutical sources, FDA/EMA approvals for genoceutical efficacy criteria with challenges, and ethical guidelines relating to gene therapy of specific rare metabolic, cancer and neurological diseases. The safety evaluation of approved genoceuticals or orphan drugs is highlighted with basic principles and ‘genovigilance’ requirements (to observe any adverse effects, side effects, developed signs/symptoms) to establish their therapeutic use. Current European Union and Food and Drug Administration guidelines continuously administer fast-track regulatory legal framework from time to time, and they monitor the success of gene therapy medical product efficacy and safety. Moreover, new ethical guidelines on ‘orphan drug-like genoceuticals’ are updated for biodistribution of the vector, genokinetics studies of the transgene product, requirements for efficacy studies in industries for market authorization, and clinical safety endpoints with their specific concerns in clinical trials or public use.