An early clinical trial of 5-ALA sonodynamic therapy in recurrent high-grade glioma

Authors

• Nader Sanai, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Artak Tovmasyan, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• An-Chi Tien, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Yu-Wei Chang, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Tigran Margaryan, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• William Knight, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Kristin Hendrickson, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Jennifer Eschbacher, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Jocelyn Harmon, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Amy Hong, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Wonsuk Yoo, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Charuta Furey, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Stuart L. Marcus, SonALAsense Inc., Oakland, CA 94607 USA.
• Lea Alhilali, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Igor Barani, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Zaman Mirzadeh, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
• Shwetal Mehta, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.

Document Type

Article

Abstract

Systemic administration of 5-aminolevulinic acid (5-ALA) results in accumulation of the sonosensitizing compound protoporphyrin IX in tumor cells because of their aberrant metabolism. Activation of protoporphyrin IX by noninvasive, magnetic resonance-guided focused ultrasound (MRgFUS) sonodynamic therapy (SDT) induces production of reactive oxygen species and tumor cytotoxicity. In this first-in-human, open-label, early clinical study (NCT04559685), safety and biological efficacy of ascending doses of MRgFUS combined with intravenous administration of 5-ALA (SONALA-001) were assessed in nine patients with recurrent high-grade glioma. The safety assessment revealed no drug-related or device-related toxicities. Pharmacokinetic analysis provided quantitative information on the concentration of 5-ALA and protoporphyrin IX in plasma, blood, and brain tissue. Comparison of pharmacodynamic markers between half of the tumor region treated with MRgFUS compared with the untreated tumor provided information on dose-related changes in markers of oxidative stress and cell death for each patient's tumor. This early phase clinical trial demonstrates proof of principle for 5-ALA SDT as a therapeutic modality for glioma. Further research is needed to optimize treatment parameters for clinical efficacy and to explore the potential of 5-ALA SDT in other types of cancer.

Medical Subject Headings

Humans; Aminolevulinic Acid (therapeutic use, pharmacokinetics, adverse effects); Glioma (therapy, pathology, drug therapy); Male; Female; Ultrasonic Therapy (methods); Middle Aged; Adult; Brain Neoplasms (therapy, pathology, drug therapy); Protoporphyrins (blood, metabolism); Neoplasm Recurrence, Local (therapy, pathology); Neoplasm Grading; Aged; Treatment Outcome

Publication Date

11-26-2025

Publication Title

Science translational medicine

E-ISSN

1946-6242

Volume

17

Issue

826

First Page

eads5813

PubMed ID

41296829

Digital Object Identifier (DOI)

10.1126/scitranslmed.ads5813

Recommended Citation

Sanai, Nader; Tovmasyan, Artak; Tien, An-Chi; Chang, Yu-Wei; Margaryan, Tigran; Knight, William; Hendrickson, Kristin; Eschbacher, Jennifer; Harmon, Jocelyn; Hong, Amy; Yoo, Wonsuk; Furey, Charuta; Marcus, Stuart L.; Alhilali, Lea; Barani, Igor; Mirzadeh, Zaman; and Mehta, Shwetal, "An early clinical trial of 5-ALA sonodynamic therapy in recurrent high-grade glioma" (2025). Neurosurgery. 2395.
https://scholar.barrowneuro.org/neurosurgery/2395