The future prospects of cell
and gene therapy

Role of Cell and Gene Therapy in Gastrointestinal Disorders

1. Inflammatory Bowel Disease (IBD) – Crohn’s Disease and Ulcerative Colitis

• • Mesenchymal Stem Cells (MSCs): MSCs have immunomodulatory properties that help in reducing inflammation and promoting tissue repair. Clinical trials have shown that MSCs can induce remission in patients with refractory Crohn’s disease by modulating immune responses and enhancing mucosal healing​
  • Hematopoietic Stem Cells (HSCs): HSC transplantation (HSCT) has been explored for severe cases of Crohn’s disease. The procedure aims to reset the immune system, thereby reducing disease activity. Although risky, it has shown promising results in inducing long-term remission in some patients​.

2. Cystic Fibrosis (CF)

• • Gene Editing (CRISPR-Cas9): CF is caused by mutations in the CFTR gene. Gene editing technologies like CRISPR-Cas9 have been used to correct these mutations in cells derived from CF patients. Preclinical studies have demonstrated that CRISPR can restore CFTR function, offering a potential cure for CF-related GI complications, such as pancreatic insufficiency and intestinal blockages​.
  • Gene Therapy Vectors: Adenoviral and lentiviral vectors have been employed to deliver functional CFTR genes to the affected cells in the GI tract. Early-phase clinical trials are ongoing to assess the safety and efficacy of these approaches​

3. Colorectal Cancer

• • CAR-T Cells: Chimeric antigen receptor (CAR) T-cell therapy has been adapted to target specific antigens expressed on colorectal cancer cells. CAR-T cells are engineered to recognize and kill cancer cells, providing a personalized immunotherapy option. Clinical trials are investigating the effectiveness of CAR-T therapy in treating metastatic colorectal cancer​.
  • Oncolytic Viruses: Gene therapy utilizing oncolytic viruses, which selectively infect and kill cancer cells, has shown promise in colorectal cancer. These viruses can be engineered to express therapeutic genes that enhance anti-tumor immune responses​ .

4. Liver Diseases – Genetic Metabolic Disorders

• • Gene Therapy for Wilson’s Disease: Wilson’s disease, caused by mutations in the ATP7B gene, leads to copper accumulation in the liver. Gene therapy approaches aim to deliver a functional copy of the ATP7B gene to liver cells, correcting the underlying genetic defect and preventing copper accumulation​.
  • Phenylketonuria (PKU): Gene therapy is being explored to correct the genetic mutation in the PAH gene responsible for PKU. Delivering a functional PAH gene to liver cells can restore the enzyme activity needed to metabolize phenylalanine, preventing the toxic buildup that causes the disease​.

5. Pediatric Intestinal Failure

• • Organoid Transplantation: Research into generating intestinal organoids from patient-derived stem cells is underway. These organoids can potentially be transplanted into patients with severe intestinal failure to restore normal gut function. This approach could offer a new avenue for treating conditions like short bowel syndrome​

6. Gastroesophageal Reflux Disease (GERD)

• • Vagal Nerve Stimulation: Gene therapy approaches are being explored to modulate the activity of the vagus nerve, which plays a role in controlling stomach acid secretion. By altering gene expression in neurons, it may be possible to reduce acid reflux symptoms more effectively than current pharmacological treatments​.