Gene therapy of amyotrophic lateral sclerosis.
Two-year experiments were performed to evaluate the neurotrophic effect of hypoxia-inducible factors (vascular endothelial growth factor and angiogenin) expressed in recombinant human adenoviruses in amyotrophic lateral sclerosis. Randomized placebo-controlled trial demonstrated safety and good tolerability of the recombinant antiviral drugs. The life span of patients under conditions of hypoxia increased after treatment with the test drug, which was probably related to improved resistance of motoneurons. The presence of virus-neutralizing antibodies decreases the effectiveness of adenoviral vectors, which necessitates differential approach to the selection of patients and continuous monitoring of gene therapy.
Zavalishin
I A
IA
Research Center of Neurology, Russian Academy of Medical Sciences, Russia.
Bochkov
N P
NP
Suslina
Z A
ZA
Zakharova
M N
MN
Tarantul
V Z
VZ
Naroditskiy
B S
BS
Suponeva
N A
NA
Illarioshkin
S N
SN
Shmarov
M M
MM
Logunov
D Y
DY
Tutyhina
I L
IL
Verkhovskaya
L V
LV
Sedova
E S
ES
Vasiliev
A V
AV
Brylev
L V
LV
Ginzburg
A L
AL
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D000808:Angiotensinogen / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019076:Transgenes / Q000235:genetics; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics
D010919:Placebos; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000808:Angiotensinogen