Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency.
| Publication Type | Academic Article |
| Authors | Matsumura Y, Stiles K, Reid J, Frenk E, Cronin S, Pagovich O, Crystal R |
| Journal | Mol Ther Methods Clin Dev |
| Volume | 15 |
| Pagination | 72-82 |
| Date Published | 08/26/2019 |
| ISSN | 2329-0501 |
| Abstract | Aldehyde dehydrogenase 2 (ALDH2) deficiency causes "Asian flush syndrome," presenting as alcohol-induced facial flushing, tachycardia, nausea, and headaches. One of the most common hereditary enzyme deficiencies, it affects 35%-40% of East Asians and 8% of the world population. ALDH2 is the key enzyme in ethanol metabolism; with ethanol challenge, the common ALDH2*2 (E487K) mutation results in accumulation of toxic acetaldehyde. ALDH2*2 heterozygotes have increased risk for upper digestive tract cancers, compounded by smoking and drinking alcohol. We hypothesized that a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) would correct the deficiency state. AAVrh.10hALDH2 was administered intravenously to Aldh2 knockout (Aldh2 -/-) and Aldh2 E487K knockin homozygous (Aldh2 E487K+/+) mice. Following acute ethanol ingestion, untreated ALDH2-deficient mice had elevated acetaldehyde levels and performed poorly in behavioral tests. In contrast, treated Aldh2 -/- and Aldh2 E487K+/+ mice had lower serum acetaldehyde levels and improved behavior. Thus, in vivo AAV-mediated ALDH2 therapy may reverse the deficiency state in ALDH2*2 individuals, eliminating the Asian flush syndrome and reducing the risk for associated disorders. |
| DOI | 10.1016/j.omtm.2019.08.004 |
| PubMed ID | 31649957 |
| PubMed Central ID | PMC6804850 |