Key Points
- A review paper shows sonodynamic therapy with 5-aminolevulinic acid as a strong potential noninvasive treatment for malignant gliomas.
- Preclinical and early clinical studies have demonstrated selective tumor destruction, preservation of healthy tissue, and good patient tolerance.
Sonodynamic Therapy Using 5-Aminolevulinic Acid for Malignant Gliomas: A Review
Malignant gliomas are aggressive brain tumors that originate from glial cells – cells that provide support, protection, and insulation for neurons. The standard of care is surgical resection, when possible, followed by chemotherapy and radiotherapy. However, the prognosis remains poor, with a median survival of less than 24 months, and new therapies are desperately needed.
What is Sonodynamic Therapy?
Sonodynamic therapy (SDT) with focused ultrasound has emerged as a promising treatment option for gliomas, particularly when the tumor is inoperable. SDT destroys tumors cells when focused ultrasound is used to activate a sonosensitizing agent that selectively accumulates in abnormal cells. Specifically, 5-aminolevulinic acid (5-ALA) has shown great potential as a sonosensitizing agent for glioblastoma due to its high selectivity for tumor cells.
A recent article authored by Andrea Ebeling, PhD, at Photonamic GmBH in Pinneberg, Germany, and Francesco Prada, MD, at Istituto Neurologico C. Besta in Milan, Italy, provides a comprehensive overview of the science behind SDT using 5-ALA, shares results from completed and ongoing preclinical and clinical studies, and outlines future directions for the technology.
Preclinical Data
Preclinical studies have demonstrated promising performance of this therapy in in vitro and in vivo settings. Multiple research teams have shown that SDT has a selective antitumor effect while preserving surrounding healthy tissue and increased survivability across a range of frequencies and intensities. Further studies have been conducted to optimize the parameters before to moving to clinical trials.
Clinical Trials
Initial clinical trials have been conducted and are currently underway for SDT with 5-ALA. A study in Phoenix, Arizona, (NCT04559685) and another in Milan, Italy (NCT04845919) are testing the safety and feasibility of Insightec’s Exablate Neuro device. Another ongoing study at the University of Virginia (NCT06039709) is using the NaviFUS device in up to 11 participants.
In addition to the Insightec and NaviFUS devices, additional studies have tested Alpheus Medical’s CV01 device. Overall, the results have shown clinical improvements and good patient tolerance with a lack of observed side effects.
Future Directions
While the field is still evolving, SDT shows great promise, and future work aims to test its versatility. Gliomas are inherently a heterogeneous group of tumors, making it important to optimize the SDT parameters for biological differences. Additionally, preclinical studies have been completed using SDT in breast, pancreatic, and liver cancer, highlighting the potential for it to be used as a treatment for a variety of cancer types. More studies are also necessary to evaluate the safety and efficacy of SDT in combination therapies, such as chemotherapy or immunotherapy.