With the fundamental mechanism established for opening the BBB with FUS and microbubbles, scientists around the world are working to advance the potential of FUS to play an integral role—either alone or in combination with other therapies—in the treatment of several neurological diseases. For example, pre-clinical research has been evaluating the use of FUS to deliver therapies to treat:

The goal of using FUS to open the BBB is to allow promising therapeutics to reach the brain. The following diseases are among those that are already under investigation:

Alzheimer’s Disease
Kullervo Hynynen and his group at Sunnybrook Health Sciences Centre in Toronto are using FUS to open the BBB for the delivery of antibodies that reduce the amount of damaging plaques that build up in the brain. They were the first to show that repeated treatments alone (no antibodies) improved spatial memory in a mouse model of Alzheimer’s disease. This work gained the attention of the NIH. They plan to translate their findings to human clinical trials, and the protocol for an initial trial is currently being developed by the Foundation’s Alzheimer’s Disease Steering Committee.

Earlier this year in Queensland, Australia, Gerhard Leinenga and Jürgen Götz published additional evidence to corroborate the Sunnybrook work, as they found similar results – reduced amyloid plaque burden plus increased memory – in a different Alzheimer’s mouse model. The Foundation wrote a Letter to the Editor in response to the study.

After completing initial parameter-setting studies, Elisa Konofagou at Columbia University is using FUS to improve delivery of neurotrophic factors to the brains of Alzheimer’s mice.

The proposed mechanism of action for FUS with Alzheimer’s disease is that it enables delivery of antibodies that facilitate the removal of amyloid plaques. Scientists also hypothesize that it may stimulate glial cells, allowing the immune system to attack and remove the unwanted amyloid plaques on its own.

Brain Cancer
Researchers at Brigham and Women’s Hospital/Harvard-MIT first found an improved anti-tumor effect in rats with glioma while using FUS to administer liposomal (encapsulated) doxorubicin. Subsequent studies found that multiple treatments showed a therapeutic effect and that the level of doxorubicin uptake was based on the size or stage of the tumor.

In Taiwan, Hao-Li Liu and his group at Chang-Gung University have been studying many varying parameters for opening the BBB to target brain tumors with either chemotherapy or immunotherapies while decreasing intracerebral hemorrhage or other types of damage. Some of their studies also include various ways of imaging the opening of the BBB.

At UVA, Rich Price is conducting laboratory research taking specially designed nanoparticles--that were developed and loaded with proteins or genes by Justin Hanes and his group at Johns Hopkins--and using FUS to treat brain tumors and Parkinson’s disease. This work had garnered $3.3 million in NIH funding by 2012, followed by additional multiple funding awards this year.

Studies now underway in Tim Bullock’s laboratory at UVA will look at the potential of FUS to enhance the effectiveness of immunotherapy in treating brain metastases emanating from melanoma.

Parkinson’s Disease
Similar to her work with Alzheimer’s mice, Elisa Konofagou at Columbia University also used FUS to improve delivery of neurotrophic factors to the brain in mice with Parkinson’s disease. This study was funded by the Foundation.


 

 

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