Farmington, Conn.-based biotech startup Lambdavision Inc. is preparing to test the benefits of microgravity in producing its protein-based artificial retina, thanks to a $5 million, three-year award from the National Aeronautics and Space Administration (NASA). The first-of-a-kind treatment aims to restore vision to people who have lost all or much of their sight due to advanced retinitis pigmentosa (RP). It is expected to have future applications in age-related macular degeneration (AMD), the leading cause of blindness in adults 55 and older.

Lambdavision, along with implementation partner Space Tango Inc., of Lexington, Ky., expects to make several trips to the International Space Station (ISS) to study production of the novel treatment in microgravity during low Earth orbit.

Both RP and AMD are characterized by the loss of photoreceptor cells, which causes the eyes to become insensitive to light. The artificial retina uses bacteriorhodopsin, a light-activated protein that mimics the light-absorbing properties of human photoreceptors. The goal is to replace the damaged cells in the retina and restore normal function, which is absorbing light and transmitting signals to the brain.

Powered by incident light

“The artificial retina is flexible and implantable and designed to be effective regardless of gene type,” Nicole Wagner, Lambdavision’s president and CEO, told BioWorld.

That’s a huge advantage with a gene-regulated disease like RP, she said, noting most R&D is targeting a gene therapy approach. “[RP] is controlled by [more than] a hundred different genes, so what we’re doing is going to be effective, regardless of the gene type.”

About the size of a hole punch, the artificial retina has another advantage over current alternatives. By using incident light as its power source, it doesn’t require external battery packs or goggles to help people see.

The artificial retina is produced via a layer-by-layer process, in which alternating layers of bacteriorhodopsin and a polymer are deposited on an ion-permeable membrane to create a high enough optical density to absorb light and generate an ion gradient that can interact and interface with the damaged neural cells in the retina.

“The idea behind utilizing microgravity, ultimately, is to improve both the stability and the performance of the artificial retina,” Jordan Greco, chief scientific officer at Lambdavision, told BioWorld. “We’ve seen that microgravity paradigms, in terms of manufacturing via layer by layer, have shown to enhance the three-dimensional assembly, increase aggregation in solutions, reduce the number of defects per layer, increase the efficiency between the binding of the layers in the film and, ultimately, this has an increase in the optical clarity of the resulting films that are generated.”

Implications for other medical products

The NASA-funded research could have implications for other medical technologies. Layer-by-layer manufacturing is seen in several products in the biomedical sector, including drug delivery systems, tissue engineering bone grafts and anti-inflammatory applications.

Lambdavision demonstrated proof of concept for its research on the ISS in 2018. The company is working with Space Tango and NASA to coordinate the first flight and experiment on the ISS under the new award, with a targeted launch in the first quarter of 2021.

The first couple of flights from the NASA award will assess the capabilities and manufacturing prototypes that are required to optimize production and pave the way for microgravity production for preclinical and clinical studies, Greco said. Because of its active ingredient, the complex is likely to follow the drug regulatory route.

Founded in 2009 on discoveries with light-activated proteins made in the laboratory of Robert Birge at the University of Connecticut, Lambdavision previously received $500,000 from Connecticut Innovations and has secured funding from the National Science Foundation and National Eye Institute. The company currently is conducting a series A round to support commercialization of the artificial retina through phase I clinical trials.

“Our hope is that we will be in the clinic within the next three to four years,” Wagner said, adding that the company anticipates hiring additional team members in R&D, manufacturing, quality assurance and other areas to support its continued growth.

One of three NASA awards

The artificial retina program is one of three biomedical engineering and automation projects to recently win NASA funding. The University of California at San Diego was awarded $5 million to develop the first dedicated stem cell research laboratory within the ISS. And Cedars-Sinai received $1.5 million to send induced pluripotent stem cells to the ISS, with the aim of seeing whether it is practical to produce large batches of stem cells in space to treat various diseases. Both organizations also are partnering with Space Tango, whose Open Orbit platform provides access to microgravity for research and commercial manufacturing applications that enhance life on Earth.

As a company that facilitates microgravity research and manufacturing, Space Tango is “looking at not only the changes in biological systems that could lead to understanding of diseases and new therapeutics, but where are those levers for manufacturing that could really change the paradigm for the industry,” Jana Stoudemire, Space Tango’s commercial innovation officer, told BioWorld. “Our goal is to build those capabilities, have the access to the microgravity environment and then put that infrastructure for GMP manufacturing in place that allows us to make products intended for human use.”

Building a compliant infrastructure

Ensuring GLP- and GMP-compliant conditions during ascent to the ISS, in orbit and return to Earth is no small order, requiring clean room facilities, tracking controls and quality systems – just as with any FDA-regulated product. “That is not easy to do terrestrially, but integrating that into the chain for a space flight is very complex,” Stoudemire said.

Space Tango envisions a new market segment for manufacturing biomedical products. “We’re moving from the R&D stage to what I would call pilot manufacturing. We’re now going to be taking raw material up and bringing something of value back,” Twyman Clements, co-founder and CEO of Space Tango, told BioWorld. “This isn’t sci-fi. These are real applications with real partners.”

Stoudemire agreed. “We have a future vision of having an automated, fully GMP-compliant manufacturing facility. Once that’s available, it does things like save companies the cost of building a facility to potentially do this improved manufacturing in.”

Given the basic cost per kilogram of sending anything into space, manufacturing aboard the ISS isn’t for everybody. “When we find products like the retinal implant that can be manufactured in a way that can’t be achieved here, that’s the starting point to have those discussions about a process makes it beneficial to want to do [work] in [a microgravity] environment,” Stoudemire said.

In Lambdavision’s case, those advantages include lack of sedimentation and shear stress that would occur in traditional culture, she explained. Microgravity also affects cell shape and cell signaling in ways not seen on Earth. Early work with the Cedars-Sinai team showed that stem cells maintain a state of pluripotency, “which, from a manufacturing standpoint, … is one of the biggest hurdles to the stem cell industry, because it’s so labor-intensive and difficult to passage those cells,” she said.

Beyond the cost, though, made-in-space products could yield rewards for companies in terms of intellectual property and tax advantages, as there is currently no tax structure for manufacturing in orbit.

“When you think about expanding the definition of global to 250 miles up, from a manufacturing standpoint there are … some additional benefits to the industry” in this economic model, she said.

Other miles-high projects

NASA’s support for biomedical research and manufacturing is not new. Last year, Interuniversity Microelectronics Centre, of Leuven, Belgium, received funding to test a technology for monitoring astronauts’ health status under zero gravity conditions using a first-ever disposable diagnostic device developed by its spin-off, Midiagnostics NV. And in January, Scorpio-V Inc., the biological sciences division of Hnu Photonics LLC, of Kahului, Hawaii, announced it will perform biological experiments on the ISS aimed at testing the effects of microgravity on neurons. The company will control and monitor the NASA-funded research from Earth.