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Ultrasound, a miracle cure for DIPG or just an add-on therapy?

Updated: Mar 10, 2023

Sharing my thoughts and data collection on Ultrasound for DIPG, as always a disclaimer that I am not a medical doctor and this is not medical advice just my thoughts, understanding, and research.

The applicable usages of ultrasound as DIPG therapy:

  1. SonALA / MRI Guided HFUS High-intensity Focused Ultrasound (Sonodynamic therapy SDT)

    1. Variation: Ultrasound (but low-intensity) + 5-ALA

  2. Opening the blood-brain barrier to deliver a chemotherapy. LFUS Low-intensity Focused Ultrasound + Microbubbles

  3. Ultrasound combined with Radiation

Focused Ultrasound (HFUS) (high-intensity) / SonALA / MRI Guided (MRgFUS)

The simple explanation for me is the known 5-ALA dye, bunds predominantly to DIPG/cancer cells (they divide much faster: high grade gliomas), and when excited with ultrasound the ultrasound-excited 5-ALA kills the cancer cells (selective malignant cell cytotoxicity; This is called photodynamic treatment (PDT))

A short explainer Video form YouTube

The SONALA-001 is a special formulation of the 5-ALA dye, which has been used as a dye /fluorescence for tumors during resection (ex. GBM) for a long time and the research in our own Javad Nazarian's lab in Zurich Children's Hospital's DIPG/DMG Center showed that the SONALA-001 dye works even better in DIPG cells than in GBM.

The questions in my head remain: what % (or which type) of the cancer cells the 5-ALA will bind to, will repeat treatments help further or not, any longer-term side effects, and clearly the MTD combination of dye and ultrasound intensity (the main target of the clinical trial referenced below)

  • A Phase 1/2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2 in Patients With DIPG clinical trial NCT05123534

    • Main target: MTD of drug+intensity: 5-15mg/kg and 200-800J of the MRgFUS (the HFUS)

    • No serious side effects were reported from the first few patients (on social media) and promising initial results for helpfully prolonged MST (Median Survival Time)

One Variation under the same principal of Ultrasound (but lowwe-intensity) with 5-ALA

This is currently excluding DIPG (brainstem tumors) and it is 18+ years of age. Still, given the HFUS above history then the applicability seems obvious and identical so moving to the brainstem tumors and pediatrics is a matter of time. The company Alpheus Medical does mention an Expanded Access Policy as Compassionate Use is still too early given the Phase 1 trial.

One of the main differences to HFUS, as I understand it, is that the Ultrasound is not focused (treating a larger area) and that the 5-ALA drug is taken orally as a solution (I am not certain, but I believe SONALA-001 is delivered through an IV)

  • A Phase 1 Study to Evaluate 5-ALA Combined With CV01 Delivery of Ultrasound in Recurrent High-Grade Glioma NCT05362409

Opening the blood-brain barrier to deliver a chemotherapy. Focused Ultrasound (LFUS) (low-intensity) with Microbubbles

The goal here is for the vibrating microbubbles to open the BBB and allow various drugs (or immune therapies) to penetrate the BBB or enter the brain in larger quantities for the BBB-penetrating drugs. Children's National is preparing to start a trial very soon (I will find a reliable source with more specifics). The best source of data so far has been the Children's National article here.

March 2023, NCT05762419 is recruiting patients with the Etoposide as a drug.

Canada, were the 1st to open such a trial "Opening the blood-brain barrier to deliver a chemotherapy link" Nov 16, 2022 Update: "Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound" trial is now open NCT05615623

A pre-clinical example with LFUS + microbubbles is this in-vivo work with Doxorubicin.

Combination with Radiation

In conclusion, ultrasound has very promising applications for DIPG as well as other tumors, but for us in the DIPG community, there is just not enough data with only a very early Phase 1 trial. So ultrasound remains one of the many bets and research areas that our community is trying to fund. To join the cause of saving thousands of children suffering from unimaginable suffering and almost certain death Donate Now to the cause and/or share this article to make DIPG a priority for more people.

As always share any updates, corrections, extensions, and ideas so I can update the article and do let me know if you want to be cited/credited for specific updates or sources.

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