Treatment of viral infections with 5-aminolevulinic acid and light.
OBJECTIVE
When 5-aminolevulinic acid (ALA) is exogenously supplied, protoporphyrin IX (PpIX) is accumulated in various cells and makes them light sensitive. The possibility of using such an approach for the treatment of viral infections was studied in this work.


METHODS
ALA was added to cultured cells infected with human immunodeficiency virus (HIV). Accumulation of PpIX in the cells as well as virus infectivity after photodynamic treatment (PDT) were assessed. For in vivo studies, guinea pigs were infected with herpes simplex virus (HSV) and then administered ALA at intervals after infection. The animals were exposed to PDT at the site of infection 3 hours after ALA administration. Clinical observations and virus titration were made daily. For clinical studies, two patients with Molluscum contagiosum and Verrucae vulgares were treated with ALA fortified with an iron chelating agent and dimethylsulfoxide, followed 4 hours later by PDT.


RESULTS
Cells that are infected with HIV accumulated PpIX upon addition of ALA in vitro. This accumulation was enhanced approximately two-fold in the presence of an iron chelator. Subsequent exposure to red light PDT drastically reduced the virus titer (> 99% for U1 cells latently infected with HIV). In guinea pigs infected with HSV, subsequent administration of ALA and exposure of the lesions to red light shortened the duration of vesicles' appearance from more than a week to a few days and reduced HSV titer in the lesions by > or = 5 log10. ALA-PDT treated AIDS patient suffering from Molluscum contagiosum or a kidney transplant patient with Verrucae vulgares showed greatly improved clinical symptoms one month after treatment.


CONCLUSIONS
It is concluded that ALA-PDT could be effective in treating certain viral infections, particularly those resulting in warts.
Smetana
Z
Z
Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
Malik
Z
Z
Orenstein
A
A
Mendelson
E
E
Ben-Hur
E
E
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D005260:Female; D006168:Guinea Pigs; D015497:HIV-1 / Q000187:drug effects; D006561:Herpes Simplex / Q000188:drug therapy; D006801:Humans; D008297:Male; D008976:Molluscum Contagiosum / Q000188:drug therapy; D010778:Photochemotherapy / Q000379:methods*; D011524:Protoporphyrins / Q000096:biosynthesis; D014777:Virus Diseases / Q000188:drug therapy*; D014860:Warts / Q000188:drug therapy
D011524:Protoporphyrins; D000622:Aminolevulinic Acid