Focused Ultrasound in Cell and Gene Therapies

Listen to Quick Takes from experts in the community on the following questions (Time: 20 min):  

• What is focused ultrasound?  

• Why is focused ultrasound a safe treatment option?  

• What are the latest advancements and clinical applications of focused ultrasound in brain disease treatments? 

• How can focused ultrasound enhance gene and cell therapy treatments for brain diseases, and what are the main challenges to making this a clinical reality? 

• For non-brain diseases, how can focused ultrasound enhance gene and cell therapy treatments and what are the main challenges to make this a clinical reality? 

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How it Works

Unlike standard ultrasound used for imaging, focused ultrasound targets and treats tissues, aiming to address medical conditions like cancer and essential tremors non-invasively (meaning no medical instruments will enter the body). 

Focused ultrasound involves high-frequency sound waves that interact with body tissues, either causing vibrations (mechanical effects) or heating tissues (thermal effects). Thermal effects are used to create small lesions in specific areas. 

Focused ultrasound can treat essential tremors by creating tiny lesions in the brain to stop the tremors. This approach is non-invasive, does not require surgery, and avoids ionizing radiation. 

Clinical trials over the past decade have demonstrated evidence for the safety of focused ultrasound. It has been FDA-approved for several applications, offering non-invasive alternatives to traditional surgeries. 

Applications of Focused Ultrasound

• Prostate Cancer: Treats prostate tumors non-invasively, using a transrectal (through the rectum) approach to preserve surrounding nerves. 

• Uterine Fibroids: Ablates fibrous masses in the uterine wall that cause symptoms like bleeding or pain, using an external transabdominal (through the abdomen) approach. 

• Bone Metastasis Pain Relief: Provides palliative pain relief for bone metastasis by targeting bone tumors.  

• Liver Metastasis: Treats colorectal cancer metastasis in the liver using a method called histotripsy, given externally through the abdomen. 

Potential and Benefits

Focused ultrasound treatments are generally performed without incisions, anesthesia is optional, and patients avoid radiation exposure, making these therapies safer than many traditional treatments. 

Focused ultrasound can deliver large therapeutic compounds and cells safely across the blood-brain barrier. It enhances bioavailability in the brain while allowing precise targeting of diseased brain areas, which is critical in disorders like ALS, Parkinson’s, and Huntington’s disease. Focused ultrasound now offers a non-invasive alternative that may achieve comparable delivery efficacy without incisions. 

Expanding Ultrasound for Gene Delivery Beyond the Brain

• Genetic diseases affecting organs like the heart (e.g., cardiomyopathy), muscles (e.g., muscular dystrophy), kidneys, and blood (e.g., sickle cell disease) are potential targets for gene therapy.  

• Unlike sickle cell treatments that utilize genetically modified bone marrow, organ-specific therapies like those for the heart and kidney require direct gene insertion into tissues. 

Challenges of Gene Delivery in Large Organs 

• Broad Coverage: Focused ultrasound, suitable for pinpoint precision (as in the brain), is less applicable for large organ-wide gene delivery. A new approach must target the entire organ rather than a localized area.  

• Selective Targeting: Ultrasound must ensure genes enter the correct cells (e.g., heart muscle cells) while avoiding uptake by unintended cell types like blood vessel or support cells. 

Ultrasound Techniques for Organ-Wide Gene Delivery

• Whole-Organ Ultrasound Exposure: Involves using ultrasound across the entire organ rather than pinpoint-focused energy.  

• Microbubble-Assisted Ultrasound: Tiny bubbles (contrast agents) vibrate in the ultrasound field to enhance gene delivery from blood vessels into targeted tissues. 

Key Research Hurdles

• 3D Ultrasound Exposure: Requires generating ultrasound fields that cover the full three-dimensional structure of an organ with adequate intensity and frequency.  

• Cellular Specificity: Developing methods to guide genes to specific cells within organs (e.g., heart muscle cells) to address diverse cell types present in large organs. 

Research and Future Directions

• Ongoing efforts aim to overcome the challenges of large-organ gene delivery by refining ultrasound techniques and optimizing targeting strategies. 

Continuing the Journey

Check out some helpful information to guide you through the exciting new field of Focused Ultrasound: 

• Focused Ultrasound Foundation  

• Search Clinicaltrials.gov for open trials researching this treatment approach  

Call to Action

Share this information among your community to help raise awareness and understanding of focused ultrasound. For more information on gene therapy, explore the rest of ASGCT's Patient Education site, which includes resources that are free to use by sharing on social media, embedding the video, or simply linking to this page! Please credit the American Society of Gene and Cell Therapy, or tag @ASGCTherapy. 

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