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Suppression of MMP-9 by doxycycline in brain arteriovenous malformations
Tomoki Hashimoto1, Melissa M Matsumoto, Jenny F Li
1Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, San Francisco, California, USA. hashimot@anesthesia.ucsf.edu
Background:
The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs).
Methods:
Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured.
Results:
Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 microg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 microg/ml = 100 +/- 6 vs 60 +/- 16 vs 61 +/- 9%; active: 100 +/- 8 vs 48 +/- 16 vs 59 +/- 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 +/- 1.94 vs 3.26 +/- 3.58, P = .50; active: 0.48 +/- 0.48 vs 0.95 +/- 1.01 ng/100 microg protein, P = .25).
Conclusions:
A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.
Insights
Doxycycline effectively reduced matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformation (AVM) tissues ex-vivo and showed a trend toward reduction in patients. Further research is needed to confirm doxycycline's clinical efficacy in AVM treatment.
Area of Science:
- Vascular Biology
- Pharmacology
- Neurosurgery
Background:
- Brain arteriovenous malformations (AVMs) are complex vascular lesions.
- Matrix metalloproteinase-9 (MMP-9) plays a role in AVM pathogenesis.
- Current treatment options for AVMs have limitations.
Purpose of the Study:
- To investigate the feasibility of using doxycycline to suppress MMP-9 in AVMs.
- To evaluate doxycycline's effect on MMP-9 levels in ex-vivo AVM tissues and in a pilot clinical trial.
Main Methods:
- Ex-vivo treatment of AVM tissues with doxycycline.
- Measurement of active and total MMP-9 levels.
- Pilot trial administering doxycycline or placebo to AVM patients prior to resection.
Main Results:
- Doxycycline significantly decreased MMP-9 levels in ex-vivo AVM tissues.
- A trend for lower MMP-9 levels was observed in patients receiving doxycycline compared to placebo.
- The observed effects suggest potential therapeutic value.
Conclusions:
- Doxycycline can decrease MMP-9 in AVM tissues at clinically relevant concentrations.
- A short course of oral doxycycline may reduce MMP-9 in AVMs.
- Further clinical trials are warranted to validate doxycycline's efficacy in AVM treatment.
