Tuesday, May 07, 2024

 

Breakthrough paves the way for next generation of vision implants



CHALMERS UNIVERSITY OF TECHNOLOGY
Professor Maria Asplund 

IMAGE: 

MARIA ASPLUND, WHO LED THE TECHNOLOGY DEVELOPMENT PART OF THE PROJECT AND IS PROFESSOR OF BIOELECTRONICS AT CHALMERS UNIVERSITY OF TECHNOLOGY IN SWEDEN.

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CREDIT: CHALMERS UNIVERSITY OF TECHNOLOGY | GABOR RICHTER





A group of researchers from Chalmers University of Technology in Sweden, University of Freiburg and the Netherlands Institute for Neuroscience have created an exceptionally small implant, with electrodes the size of a single neuron that can also remain intact in the body over time – a unique combination that holds promise for future vision implants for the blind.

 

Often when a person is blind, some or part of the eye is damaged, but the visual cortex in the brain is still functioning and waiting for input. When considering brain stimulation for sight restoration, there needs to be thousands of electrodes going into an implant to build up enough information for an image. By sending electrical impulses via an implant to the visual cortex of the brain, an image can be created, and each electrode would represent one pixel.

 

“This image would not be the world as someone with full vision would be able to see it. The image created by electrical impulses would be like the matrix board on a highway, a dark space and some spots that would light up depending on the information you are given. The more electrodes that ‘feed’ into it, the better the image would be,” says Maria Asplund, who led the technology development part of the project and is Professor of Bioelectronics at Chalmers University of Technology in Sweden.

 

The vision implant created in this study can be described as a ‘thread’ with many electrodes placed in a row, one after the other. In the long term you would need several threads with thousands of electrodes connected to each one, and the results of this study are a key step towards such an implant.

 

The future of vision implants

An electrical implant to improve vision in people with blindness is not a new concept. However, the implant technology currently being explored in human patients is from the 1990s and there are several factors that need to be improved, for example the bulky size, scarring in the brain due to their large size, materials corroding over time and materials being too rigid.

 

By creating a really small electrode the size of a single neuron, researchers have the potential to fit lots of electrodes onto a single implant and build up a more detailed image for the user. The unique mix of flexible, non-corrosive materials make this a long-term solution for vision implants.

 

“Miniaturisation of vision implant components is essential. Especially the electrodes, as they need to be small enough to be able to resolve stimulation to large numbers of spots in the ‘brain visual areas’. The main research question for the team was, ‘can we fit that many electrodes on an implant with the materials we have and make it small enough and also effective?’ and the answer from this study was – yes,” says Professor Asplund.

 

The smaller the size, the worse the corrosion

To create an electrical implant on such a small scale comes with its challenges, especially in a tough environment, such as the human body. The major obstacle is not to make the electrodes small, but to make such small electrodes last a long time in a moist, humid environment.  Corrosion of metals in surgical implants is a huge problem, and because the metal is the functional part, as well as the corroding part, the amount of metal is key. The electrical implant that Asplund and her team have created measures in at a miniscule 40 micrometers wide and 10 micrometers thick, like a split hair, with the metal parts being only a few hundred nanometers in thickness And since there is so little metal in the super tiny vision electrode, it cannot ‘afford’ to corrode at all, otherwise it would stop working.

In the past, this problem has not been possible to solve. But now, the research team have created a unique mix of materials layered up together that do not corrode. This includes a conducting polymer to transduce the electrical stimulation required for the implant to work, to electrical responses in the neurons. The polymer forms a protective layer on the metal and makes the electrode much more resilient to corrosion, essentially a protective layer of plastic covering the metal.

 

“The conducting polymer metal combination we have implemented is revolutionary for vision implants as it would mean they hopefully could remain functional for the entire implant life-time. We now know it is possible to make electrodes as small as a neuron (nerve cell) and keep this electrode effectively working in the brain over very long timespans, which is promising since this has been missing until now. The next step will be to create an implant that can have connections for 1000s of electrodes,” says Asplund, something that is currently explored within a larger team in the ongoing EU project Neuraviper.

 

More about: the study method

The method was implemented by the research collaborators at the Netherlands Institute for Neuroscience, where mice were trained to respond to an electrical impulse to the visual cortex of the brain. The study showed that not only could the mice learn to react to the stimulation applied via the electrodes in just a few sessions, but the minimal current threshold for which mice reported a perception was lower than standard metal-based implants. The research team further reported that the functionality of the implant stayed stable over time, for one mouse even until the end of its natural lifespan.

 

More about the research:

The research has been published in the article: "Flexible Polymer Electrodes for Stable Prosthetic Visual Perception in Mice" published in Advanced Healthcare Materials. It is written by Corinne Orlemann, Christian Boehler, Roxana N. Kooijmans, Bingshuo Li, Maria Asplund and Pieter R. Roelfsema. The authors are active at the Netherlands Institute for Neuroscience, University of Freiburg and Chalmers University of Technology.

 

For more information, please contact: 

Maria Asplund, Professor, Electronics Material and Systems, Microtechnology and Nanoscience, Chalmers University of Technology, Sweden maria.asplund@chalmers.se  +46 31 772 41 14

 

Pieter R. Roelfsema, Department of Vision and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands p.roelfsema@nin.knaw.nl

 

The Chalmers contact person speaks English and Swedish, and is available for live and pre-recorded interviews. At Chalmers, we have podcast studios and broadcast filming equipment on site and would be able to assist a request for a television, radio or podcast interview.

 

Collage CAPTION: The exceptionally small vision implant created in this study uses electrical impulses to stimulate the visual cortex of the brain, where information is converted into visual impressions, like pixels on a highway matrix board.  Lower left corner: figure from the study - electrodes the size of a neuron are placed on implant “threads” as small as half a strand of hair. The implant is made of a non-corrosive material paving the way for a permanent – and more efficient - solution for the blind. 

 

Collage CREDIT: top left eye: Unsplash, lower left: Chalmers University of Technology\ Maria Asplund, right illustration: iStock

 

 

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Participants of pioneering CRISPR gene editing trial see vision improve


OHSU scientist: Results show CRISPR can treat inherited retinal disease, support further research



OREGON HEALTH & SCIENCE UNIVERSITY





About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of blindness, according to a paper published today in the New England Journal of Medicine.

 

Mark Pennesi, M.D., Ph.D. (OHSU)

“This trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration,” said Mark Pennesi, M.D., Ph.D., a corresponding author on the paper, an ophthalmologist and Oregon Health & Science University’s lead scientist for the Phase 1/2 BRILLIANCE trial. “There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment. One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights.

“While these types of tasks might seem trivial to those who are normally sighted, such improvements can have a huge impact on quality of life for those with low vision.”

The BRILLIANCE trial evaluated the safety and effectiveness of EDIT-101, an experimental gene editing treatment developed by Editas Medicine that uses CRISPR technology. The experimental treatment was designed to edit a mutation in the CEP290 gene, which provides instructions to create a protein that is critical for sight.

People with this gene mutation have a rare condition that is commonly called Leber Congenital Amaurosis, or LCA, Type 10, for which there is currently no Food and Drug Administration-approved treatment. LCA’s various types occur in about 2 or 3 out of 100,000 newborns.

Learn more about how OHSU is a leader in eye health care and research.

The OHSU Casey Eye Institute treated the trial’s first participant in early 2020. That procedure also marked the first time that CRISPR had been used to edit genes within the human body, called in vivo gene editing.

The new paper describes the study’s findings through February 2023 and details how the trial’s 14 participants — 12 adults and two children — responded to receiving EDIT-101 in one eye. Key results include:

  • 11 participants, about 79%, showed improvement in at least one of four measured outcomes.
  • 6 participants, about 43%, showed improvement in two or more outcomes.
  • 6 participants, about 43%, reported improved vision-related quality of life.
  • 4 participants, about 29%, had clinically meaningful improvement in visual acuity, or how well they could identify objects or letters on a chart.
  • There were no serious adverse events related to the treatment.
  • Most adverse events were mild or moderate, and all have since been resolved.

Four specific outcomes were used to evaluate the experimental treatment’s effectiveness:

  • Visual acuity
  • How well participants saw colored points of light while looking into a specialized device, which scientists call a full-field test
  • How well participants navigated a research maze with physical objects and varying amounts of light
  • How much participants reported experiencing improved quality of life

Further research for a future treatment

In November 2022, trial sponsor Editas Medicine announced that it was pausing the trial’s enrollment and would seek another partner to continue the experimental therapy’s development. Pennesi and colleagues are exploring working with other commercial partners to conduct additional trials, in collaboration with Editas. The researchers hope future studies can examine ideal dosing, whether a treatment effect is more pronounced in certain age groups such as younger patients, and include refined endpoints to measure impacts on activities of daily living.

“This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,” said Mass Eye & Ear ophthalmologist Eric Pierce, M.D., Ph.D., who is also a corresponding author. “While more research is needed to determine who may benefit most, we consider the early results promising. To hear from several participants how thrilled they were that they could finally see the food on their plates — that is a big deal. These were individuals who could not read any lines on an eye chart and who had no treatment options, which is the unfortunate reality for most people with inherited retinal disorders.”

“Our patients are the first congenitally blind children to be treated with gene editing, which significantly improved their daytime vision,” said the paper’s third corresponding author, Tomas S. Aleman, M.D., a pediatric ophthalmologist at the Children’s Hospital of Philadelphia and the University of Pennsylvania’s Scheie Eye Institute. “Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision. This trial represents a landmark in the treatment of genetic disease, in specific genetic blindness, by offering important alternative treatment when traditional forms of therapy, such as gene augmentation, are not an option.”

“The results from the BRILLIANCE trial provide proof of concept and important learnings for the development of new and innovative medicines for inherited retinal diseases. We’ve demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and have clinically meaningful outcomes,” said Editas Medicine Chief Medical Officer Baisong Mei, M.D., Ph.D.

The OHSU Casey Eye Institute is one of five clinical sites that recruited participants for the trial. The other sites are: Bascom Palmer Eye Institute in Miami, Florida; Mass Eye and Ear in Boston, Massachusetts; Scheie Eye Institute at the University of Pennsylvania and Children’s Hospital of Philadelphia; and Kellogg Eye Center in Ann Arbor, Michigan.

More information is also available from Mass Eye and Ear and Penn Medicine.

REFERENCE: Eric A. Pierce, Tomas S. Aleman, Kanishka T. Jayasundera, Bright S. Ashimatey, Keunpyo Kim, Alia Rashid, Michael Jaskolka, Rene L. Myers, Bryon L. Lam, Steven T. Bailey, Jason I. Commander, Andreas K. Lauer, Albert M. Maguire, Mark E. Pennesi, Gene-editing for CEP290-associated Retinal Degeneration, New England Journal of Medicine, May 6, 2023, DOI: 10.1056/NEJMoa2309915, https://www.nejm.org/doi/full/10.1056/NEJMoa2309915.

This research was supported by Editas Medicine, the National Institutes of Health’s National Eye Institute (grants P30 EY014104 and P30 EY010572), Malcolm M. Marquis MD Endowed Fund for Innovation, Research to Prevent Blindness (unrestricted grants to OHSU Casey Eye Institute and University of Pennsylvania’s Scheie Eye Institute), the Irene Heinz Given and John LaPorte Given Endowment, and Hope for Vision.

This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

In the interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regards to this research, Dr. Mark Pennesi has received payments for consulting from Editas Medicine. Review details of OHSU's conflict of interest program to find out more about how we manage these business relationships.

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