Title:Innovative Genoceuticals in Human Gene Therapy Solutions: Challenges
and Safe Clinical Trials of Orphan Gene Therapy Products
Volume: 24
Issue: 1
Author(s): Rakesh Sharma*
Affiliation:
- Surgery NMR Lab, Plastic Surgery Research, Massachusetts General Hospital, Boston, MA 02114, USA
- CCSU, Government Medical College, Saharanpur, 247232 India
Keywords:
Genoceuticals, genovigilence, gene therapy products, nucleic acid therapy, mechanism of gene therapy, clinical trials, innovations and solutions in gene therapy.
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 lessknown
‘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.
