Urinary Urgency And Frequent Urination: Gene Editing + LED Irradiation

- Jan 10, 2019-

Researchers in China and the United States have restored normal bladder function in rats with frequent and urgent urination by implanting light stimulator. This study demonstrates a new system for clinical treatment, which is expected to expand into cardiac assistance and weight management in the future.

Relevant papers were published in the world's top academic journal, Nature, on the morning of January 3, Beijing time.

The clinical manifestations of overactive bladder are urgency and frequency of urination, occasionally accompanied by urinary incontinence. The traditional treatment is continuous electrical stimulation, but it may cause pain or miss-target effect.

The joint team of Northwest University, Washington University, Massachusetts Institute of Technology and Beijing University of Aeronautics and Astronautics abandoned direct electrical stimulation therapy and chose an emerging biological tool: photogenetics. That is, by editing genes in cells, they can respond to the stimulation of light. In this case, the edited bladder neurons inhibit nerve activity under light.

To this end, researchers implanted an LED light device in the abdominal cavity of rats infected by artificial drugs, connected with a highly sensitive sensor. The sensor is made of flexible material, which monitors the data around the bladder in real time and transmits it to the external recorder wirelessly.

Once the recorder detects abnormal bladder signals, such as unnecessary frequent emptying of the bladder, it sends a wireless signal to the LED lamp in the abdomen of the rat to turn on the light. The bladder nerve cells edited by photogenetics in advance inhibit the corresponding urination under light.

The whole implanted system is powered by a wireless charging device.


Soft "Closed-loop System"

This is called a "closed-loop system" in bioengineering: the output signal in the system is also an input signal, just as the volume of the rat bladder is output by the sensor and then feedback back to be regulated by light.

Closed-loop system has significant clinical advantages: light stimulation can only be triggered when necessary to provide real-time and targeted treatment.

In the experiment, researchers injected the drug cyclophosphamide into rats, which triggered inflammation and increased bladder emptying. The system detects abnormal bladder and triggers inhibition mechanism by light, thus restoring normal frequency of urination.

The rats tolerated the whole system well, and no obvious inflammation, weight change or abnormal movement were observed 7 days after implantation.

It is worth mentioning that this achievement can only be achieved by integrating a number of emerging technologies. The first difficulty is to fabricate flexible electronic devices with good extensibility in order to measure organ changes without affecting organ functions. In addition, wireless data transmission and wireless charging are also the key conditions for optogenetics tools to develop in vivo.


Rats with implantation devices

Ellen T. Roche of MIT's Institute of Medical Engineering and Scientific Research affirmed the breakthrough of this achievement in a related commentary article: for the first time, a stable "closed-loop system" was developed to monitor and treat specific diseases. However, Roche cautions that there are still a number of problems to overcome if the rat experiment is to be scaled up and replicated in human clinical practice.

For example, the wireless charging device in the study was placed at the bottom of the rat cage, which could not meet the needs of normal human activities. After surgical incision of the abdomen of rats exposed to bladder, the researchers injected a specific virus into the bladder cells for photogenetic editing, and then re-implanted the closed-loop system. Such repetitive surgery is not practical in human clinic. Finally, in case of equipment failure, how to repair and replace the problem should also be considered.

Whether the implantation device will affect the organs in rats and cause inflammation or proliferation of surrounding tissues remains to be observed for a long time.

Despite these current obstacles, Roche has made a good outlook for this kind of closed-loop system. Existing experiments have proved that flexible electronic devices can read the physical data of rabbit hearts cultured in vitro. In the future, with implantable devices similar to bladder sensors, people may be able to adjust the activity of artificial heart assist devices in real time.

In addition, if the flexible sensor can read the deformation of the stomach and control the nerve cells to produce satiety accordingly, it may become a new way of weight loss management.