2025-03-17 アメリカ国立衛生研究所(NIH)
米国国立衛生研究所(NIH)による新たな研究で、尿酸が急性虚血性脳卒中の新たな治療法として有望であることが示されました。
虚血性脳卒中は、血栓などによって脳への血流が遮断されることで発生し、アメリカでは主要な障害および死亡原因となっています。現在の治療法は、血栓を溶解または除去し、脳への血流を回復させることに焦点を当てていますが、全ての患者が完全に回復するわけではありません。そのため、脳組織を保護する追加の治療法の開発が求められています。
この研究では、尿酸が脳組織を保護する可能性が示唆されており、今後の臨床試験での検証が期待されています。 これにより、標準的な治療法と組み合わせて、患者の回復を大幅に改善する可能性があります。
<関連情報>
- https://www.nih.gov/news-events/news-releases/nih-funded-study-identifies-potential-new-stroke-treatment
- https://www.ahajournals.org/doi/10.1161/STROKEAHA.124.048748
多施設共同前臨床試験において、尿酸による脳卒中脳保護作用は性別、年齢、合併症を超越した Uric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial
Rakesh B. Patel, PhD, Mariia Kumskova, MD, Hanish Kodali, PhD, Ivan Budnik, MD, PhD, Vitalii Kuznetsov, Aditi Jain, PhD, Abhishek Jha, PhD, …
Stroke Published: 17 March 2025
DOI:https://doi.org/10.1161/STROKEAHA.124.048748
Graphical Abstract
Abstract
BACKGROUND:
Past failures in translating stroke cerebroprotection provoked calls for a more rigorous methodological approach, leading to the stroke preclinical assessment network SPAN (Stroke Preclinical Assessment Network), where uric acid (UA) treatment exceeded a prespecified efficacy boundary for the primary functional outcome. Still, successful translation to humans requires confirmation of the effect of UA across key biological variables relevant to patients with stroke.
METHODS:
We measured the effects of intravenous UA treatment (16 mg/kg) versus intravenous saline in groups of animals enrolled in the SPAN network with diverse comorbidities, sex, and age. The masked study drug or placebo was administered during reperfusion in rodents undergoing a transient middle cerebral artery filament occlusion. The primary outcome was the modified corner test index at day 30 poststroke, and numerous secondary outcomes were collected. A modified intention-to-treat population was used in the analysis. We tested for any interactions with sex, age, and comorbidities (obesity-induced hyperglycemia and hypertension).
RESULTS:
In total, 710 animals were randomized to receive either intravenous UA or saline. After accounting for procedural dropouts and exclusions from treatment, a total of 687 animals were qualified and analyzed, including 458 assigned to UA and 229 to intravenous saline control. UA-treated animals exhibited a better primary functional outcome at day 30 (probability, 0.56 [95% CI, 0.52–0.60]; P=0.006). UA-treated animals also had a better corner test index at day 7 (probability, 0.55 [95% CI, 0.5–0.59]; P=0.035) and a higher survival rate at day 30 (hazard ratio, 1.41 [95% CI, 1.08–1.83]; P=0.011). Brain morphometry at day 2 and 30 was comparable between the treatment groups. The improved functional outcome and survival in UA-treated animals were preserved across different species, sexes, ages, and comorbidities.
CONCLUSIONS:
UA provides ischemic stroke cerebroprotection across key relevant biological variables, making it a promising intervention to be further tested in human clinical trials.
