Paralyzed monkeys walk again

Researchers are now moving towards human trials.

Two monkeys who had suffered a spinal-cord injury have had movement restored in their paralyzed leg and regained the ability to walk. The study published in Nature, used an implantable device, termed brain-spine interface, to decode signals from the brain and restore movements of the paralyzed leg. Furthermore, many of the components used in the device have already been approved for research in humans and the leader of the study, Prof. Gregoire Courtine, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, expects “to test brain-spine interface in a clinical trial within the next ten years.” Medtronic, Brown University, Fraunhofer ICT-IMM, University of Bordeaux, Motac Neuroscience and the Lausanne University Hospital (CHUV) also contributed.

We spoke to Tomislav Milekovic, one of the lead authors of the study, about the Nature article. You follow the group's research in their project on ResearchGate.

ResearchGate: Can you give us a brief insight into the results of your new study? What about this excites you the most?

Tomislav Milekovic: We showed that a brain-spine interface can restore walking in non-human primates with a spinal cord injury. The brain-spine interface acts as a bridge over the spinal cord injury by interpreting movement intentions from the brain signals and stimulating the spinal cord in order to reinforce those intended movements.

Confirming the effectiveness of this approach in non-human primates opens the prospects of developing and testing a brain-spine interface therapy for people with paraplegia. All the devices that were used in our study have been or are in the process of being approved for clinical use, thus making clinical trials soon possible. A future in which people with paraplegia use brain-spine interface to walk again is exciting.

Grégoire Courtine holds a silicon model of a primate’s brain and a brain implant. The brain-spine interface uses a microelectrode array like this one to detect spiking activity of the brain’s motor cortex. Credit: Alain Herzog / EPFL
Grégoire Courtine holds a silicon model of a primate’s brain and a brain implant. The brain-spine interface uses a microelectrode array like this one to detect spiking activity of the brain’s motor cortex. Credit: Alain Herzog / EPFL.

RG: What was the most challenging aspect of the study? 

Milekovic: The effectiveness of the brain-spine interface relies on the accurate delivery of spinal cord stimulation, based on the movement intentions decoded from the brain signals. This process is controlled by a software application that collects brain signals from 96 electrodes at 30 000 samples per second, processes all the data in real time and then makes the decision whether one of the intended movements has been identified in the brain signals. Developing a software application that could robustly perform these operations was very challenging.

RG: Have you helped other animals to walk before?

Milekovic: Courtine lab has been working on restoring walking in paralyzed rats over the last ten years. A Nature Neuroscience study in 2009 showed that epidural spinal cord stimulation can restore locomotion of paralyzed rats. A following study published in Science in 2012 showed that a similar approach can restore voluntary leg movements in paralyzed rats. The versatility of the epidural spinal cord stimulation approach was demonstrated in a 2014 study published in Science Translational Medicine, where paralyzed rats climbed the staircases with the help of computer-controlled stimulation. A study published earlier this year showed the clear benefits of spatially and temporally modulated spinal cord stimulation over a continuous stimulation delivered only over specific locations.

The knowledge and experience gained from these rat studies was crucial in designing and implementing a brain-spine interface system in non-human primates and will be vital for the development of the clinical brain-spine interface system that will one day be tested in people with paralysis.

RG: Why were monkeys used for this study? 

Milekovic: During primate evolution, the motor cortex and its axonal projections became increasingly involved in the production of complex, dexterous and precise voluntary movement. While rodents do not rely on the integrity of the motor cortex or corticospinal tract for movement, nonhuman primates and humans exhibit permanent deficits in gait control even after small cortical lesions. Therefore, non-human primate models are critical in translating therapies developed in animal models to people with paralysis.

The brain-spine interface uses a brain implant like this one to detect spiking activity of the brain’s motor cortex. Seen here, a microelectrode array and a silicon model of a primate’s brain. Credit: Alain Herzog / EPFL
The brain-spine interface uses a brain implant like this one to detect spiking activity of the brain’s motor cortex. Seen here, a microelectrode array and a silicon model of a primate’s brain. Credit: Alain Herzog / EPFL.

RG: What types of injuries could this potentially fix?

Milekovic: The brain-spine interface will be most effective when reinforcing the descending motor commands that survived the injury. In the majority of spinal cord injuries, some portion of the descending motor axons remain preserved. For example, large percentage of spinal cord injuries are contusions suffered in working or driving accidents, and majority of those people have some portion of descending connections spared. Potentially, all of the people with remaining descending motor axons could be helped by the brain-spine interface.

RG: What’s next for your research? When could this go to human clinical trials?

Milekovic: Courtine lab has already begun a feasibility clinical study at the Lausanne University Hospital (CHUV) in Switzerland to test the therapeutic effects of the spatiotemporally modulated spinal cord stimulation in people with spinal cord injury (https://clinicaltrials.gov/ct2/show/NCT02936453). In this clinical study, the stimulation is triggered using residual movements, rather than controlled using the brain signals.

In parallel, we will continue improving the brain-spine interface and the devices that are a part of it, and work to secure regulatory approvals and funding for a clinical trial to test the feasibility and efficacy of a therapy based on a brain-spine interface. If everything proceeds as planned, we expect to test brain-spine interface in a clinical trial in the next ten years.



Featured image courtesy of flickr.