| Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc |
| Journal website https://www.jocmr.org |
Review
Volume 15, Number 2, February 2023, pages 76-83
Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy
Table
| HCU: homocystinuria; CBS: cystathionine beta synthase; 3D: three dimensional. | ||
| Supplemental and dietetic aspects | Pyridoxine | a) pyridoxin responsive and b) non responsive cases |
| Vitamin D | a)/b): diet is different | |
| Folic acid | ||
| Vitamin B12 | ||
| Chaperones (small ligands) | Betaine anhydrate, sorbitol, proline, glycerol, aminolaevulinic acid, taurine, trehalose, Buphenyl, 4-phenylbutyrate | Methyldonators with lowering levels of homocysteine [28, 65, 66] |
| Proteasome inhibitors and probiotic treatment | Bortezomib (Velcade) and SYNB 1353 | Both therapy options are in preclinical study as treatment option in HCU [52, 53, 62-64] |
| Enzyme replacement therapy | Pegtibatinase (OT-58) | PEG-ylated recombinant |
| Subcutaneous application | ||
| Pegtarviliase | Up to 55% reduction of homocysteine levels after 12 weeks of application in recent preclinical studies [21, 47] | |
| CDX-6512 | ||
| Erymethionase | Erymethionase lowers both levels of homocysteine and methionine in blood plasma as first drug and is in preclinical study [68] | |
| Liver-directed therapy | Future research focus on 3D bioprinting and liver tissue engineering [75-79] | In vitro engineering of liver organoids with normal CBS enzyme activity |
| Implantation of liver organoids with normal CBS activity in the future | ||
| Cells for liver regeneration | Transplantation of liver progenitor cells (stem cells) isolated from bone marrow [71-79]. | |
| Liver transplantation | Small population surgically treated with liver transplantation to date; danger of postoperative side effects; one adult patient with primary underlying cancer disease and domino liver Tx [39, 54-56] | |
| Gene therapy | Mutation repair | Gene therapy is still in childhood shoes, studies focus on adenovirus-associated gene transfer or mini circle DNA vector in mice are confidential [67-70]; one-time approach would be desirable [37, 56-58, 61]. |
| Gene editing (CRISP-Cas 9) | ||
| Adenovirus-associated gene transfer | ||
| Mini-circle DNA vector gene transfer | ||