By Charlene N. Rivera-Bonet, Waisman Science Writer
Multiple discoveries born from the minds and hard work of Waisman Center investigators have left the nest to become successful companies or products that have had a significant impact in the world through translational research.
In 1990, physician scientist Jon Wolff, MD, made a discovery on delivering DNA to muscle cells that revolutionized gene therapy and was eventually fundamental to the development of the COVID-19 vaccines. The late Waisman Center investigator and his colleagues found a new way of delivering genetic material – DNA and mRNA – into muscles. Later on, Wolff continued to develop gene delivery technologies that became the gold standard in the field, demonstrating a higher efficiency than the existing viral vectors.
Wolff became internationally distinguished in the field for his role in advancing gene therapy. His work and discoveries led to the development of a company, Mirus Bio, which Wolff co-founded along with two colleagues. Mirus Bio, heavily influenced by the research done in Wolff’s lab at the Waisman Center, continues to develop innovative non-viral gene delivery technologies for research in gene therapy.
Like Wolff, multiple scientists at the Waisman Center, University of Wisconsin-Madison have developed companies, products, or therapies that have spun out of many years of research.
BrainXell
Su-Chun Zhang, MD, PhD, professor of neuroscience and neurology and Waisman Center investigator, has always had the desire and motivation to translate his research and discoveries to therapeutics for patients. “But the more you work on it, the more you realize it’s nearly impossible for a researcher to get things into clinics regardless how well you perform. You need another step,” Zhang says. “If you look at it historically, most of the translation needs to go through industry.”
Zhang, a pioneer in stem cell research, was the first in the world to develop neurons from embryonic stem cells in 2001. Since then, his lab has developed most of neural cell types, which they use to study disease mechanisms and design therapeutics.
In 2013 Zhang decided to take the industry route to get his research into the clinics. The opportunity arose as the then-chancellor of UW-Madison Rebecca Blank initiated a program called Discovery to Product (D2P), which provides resources to help transform innovations developed at UW-Madison into products and services. “I submitted a proposal and my proposal was selected in the top dozen. But at that time because of an injury, I was hospitalized,” Zhang says.
Zhang suffered significant injuries as a result of a bike accident, and was hospitalized when it came time to defend the proposal. “I saw it in my email, but I could not respond because I was paralyzed,” Zhang says.
Marsha Mailick, PhD, director of the Waisman Center at the time, visited Zhang at the hospital and mentioned his proposal had been selected, but he could not get the money unless he defended it. “So, I said ‘why not? I will go and defend,’” Zhang says, who asked his son for help to “sneak out” of his hospital room in a wheelchair.
When presenting in front of the D2P committee, Zhang was asked why he wanted to start a company. “I said ‘Look at me. Do you see me? Do you see my condition or what I am now? I’m in a wheelchair,’” Zhang said, while explaining that his goal was to help people that were in his same position.
“In the presentation I got so excited I forgot I was sitting in my wheelchair and actually I stood up,” Zhang says. Whether it was his determination or his presentation skills, the proposal was accepted and he got the startup money.
The company, BrainXell (pronounced brain cell) provides a range of induced pluripotent stem cell (iPSC) derived human neurons for research and therapy development, with a focus on drug discovery. They also work on developing stem cell therapies for neurological injuries and diseases through his new startup BrainXell Therapeutics (https://brainxelltx.com/) as well as in collaboration with pharmaceutical and healthcare industries.
During the second year, the company generating revenue. “The good part is that our research is solid and then when it translates to products it’s also solid,” Zhang says. “From the beginning my goal hasn’t been about making money. My goal is to translate my discoveries from research to therapeutics for patients.”
Opsis Therapeutics
David Gamm, MD, PhD, professor of ophthalmology and visual sciences, director of the McPherson Eye Research Institute, and Waisman investigator, has a goal of treating patients with currently incurable blinding diseases such as retinitis pigmentosa and age-related macular degeneration. Like Zhang, he uses stem cells to research disease mechanisms and develop therapeutics. His lab was the first to generate and patent three-dimensional retinal organoids containing photoreceptors from embryonic and induced pluripotent stem (iPS) cells.
“The combination of being at the forefront of stem cell technology and being able to demonstrate through multiple studies that the retinal cells we produce are authentic – that is, that they’re capable of serving the same functions as the retinal cells in our own eyes – led to interest from industry,” Gamm says.
It was Cellular Dynamics International (CDI), a company founded by stem cell pioneer and UW-Madison professor James Thompson, PhD, that first approached Gamm. In 2016, Fujifilm, which bought CDI, contacted Gamm with an interest in using iPS cell-derived retinal cells such as photoreceptors and retinal pigment epithelium as a potential therapy. “I was very interested in the idea since it represented the culmination of much of our work here at Waisman,” Gamm says. As part of the agreement, Opsis Therapeutics was developed as the first non-wholly owned subsidiary of Fujifilm, with partial ownership by Gamm.
Opsis, in close collaboration with Fujifilm-CDI (FCDI), provides resources and know-how at an entirely different scale compared to academia, Gamm says. It builds upon advances by FCDI that enable scalable manufacturing of authentic human retinal cells derived from iPSC. “It started out here at the Waisman Center and then grew to a local company in Madison imbedded within yet another company spun-off from the university (CDI). But now it’s an effort that involves companies in Tokyo, Boston, and Germany, with Madison being the hub. One of the best things about this long and interesting process is that it was homegrown,” Gamm says.
Opsis and Gamm’s lab at the Waisman Center continue to interact through a sponsored research agreement, which means Opsis funds projects that are related to the company. For Gamm, being part of the Waisman Center with a community of accomplished stem cell researchers such as Zhang was essential in advancing his efforts to develop authentic retinal cells.
Transitioning Together
Being such an interdisciplinary center, research at Waisman has a wide range of applications that impact multiple neurological disorders and intellectual and developmental disabilities.
Leann DaWalt, PhD, director of the Waisman Center University Center for Excellence in Developmental Disabilities (UCEDD) and a Waisman investigator, developed a multi-family group psychoeducation intervention for families of adolescents on the autism spectrum. This intervention, Transitioning Together, is now implemented beyond the Waisman Center.
Transitioning Together focuses on the transition into adulthood for autistic individuals, which can be a time of stress and challenge for them and their families. There is also a significant loss of services for autistic young adults as they graduate from high school.
The intervention resulted from 14 years of longitudinal research study that started in 1998. “The hope was to be able to take that information and develop an intervention,” says DaWalt. The longitudinal study, Adolescents & Adults with Autism: A Study of Family Caregiving, was first initiated and led by Marsha Mailick, PhD, and Jan Greenberg, PhD, and included 406 families of adolescents with ASD. It looked into understanding the developmental course of autism and the impact of autism on the family. The results of this research provided insight into what factors promote positive outcomes for autistic individuals and their families.
In 2009, DaWalt and her research group translated these findings into practice by developing the innovative, family-centered program.
The development of Transitioning Together first consisted of focus groups to learn about core family needs. After forming a curriculum based on those needs, they tested its feasibility and effectiveness through a pilot study partially funded by the Institute for Clinical and Translational Research (ICTR) at UW-Madison.
Upon successful pilot studies – feasible implementation, high satisfaction in families, full program completion – DaWalt and her colleagues developed the full intervention curriculum for Transitioning Together. The curriculum is now being implemented nationwide and in Canada.
The implementation of Transitioning Together in different sites involves training and ongoing coaching of social workers, psychologists, and other professionals that provide the curriculum. Each site pays for the training, ongoing coaching, and access to a website containing all of the materials they need.
In order to work effectively, the curriculum also has to be adapted to each site. “One of the most important pieces with implementing this outside of Madison is helping people understand that the services need to be locally based,” DaWalt says. This includes localizing examples, identifying local resources, and using culturally relevant support. The curriculum is also available in Spanish and has been expanded to use with young adults through the Working Together curriculum.
So far, all studies on Transitioning Together have found that it is a beneficial tool. Families that go through the program display significant improvement in adolescent social engagement and parental problem solving. Additionally, there is reduced parental depressive symptoms and an improvement in attitude about their teenagers.
SALT Software
Prior to Jon Miller, PhD, CCC-SLP, emeritus professor of communication sciences and disorders and former Waisman investigator, there wasn’t any quantitative method of assessing kids’ language and communication. After 10 years of working in developmental disabilities clinics Miller developed what he calls the “Blue Book.” It detailed methods of language assessments developed by Miller and colleagues to document the communication abilities of children with developmental disabilities.
Up to that point, the analysis process of children’s free speech required taking handwritten notes and counting each of their words by hand. It was prone to error and took about 20-30 hours depending on the complexity of the analysis, the number of words, the sample size, and the severity of the child’s language challenges. Miller knew he had to come up with a way to do this more efficiently. “Computers were really the deal,” Miller says, who asked a computer sciences student for help to come up with a good solution.
“This kid came by and in two weeks he had a version of [a program],” says Miller. The program was based on the findings recorded in the Blue Book. The program was able to analyze a sample of speech that would typically take days in just four to five minutes. The program wasn’t perfect and was far from user friendly, but it had a lot of potential.
For the following few years, Miller and a group of scientists and programmers including Robin Chapman, PhD, and Ann Nockerts worked on making the program, named Systematic Analysis of Language Transcripts (SALT), better. And they did. Analysis of language using SALT could reveal the process of typical vocabulary development, and help pinpoint what is going on in the language development of kids with intellectual and developmental disabilities. “As soon as we got SALT done and told anybody about it, they wanted a copy,” Miller says.
As the demand for SALT began to grow, calls to the lab for technical support started getting harder to keep up with. In order to solve this, they started charging for the product so they could hire students to answer the phone and solve consumer problems. “SALT became an enterprise,” Miller says.
It wasn’t until Miller was ready to retire from academia that he considered starting a business along with Nockerts. The Business School at UW-Madison provided support as the company started and offered courses on writing business plans that Miller took advantage of. Miller and Nockerts got full ownership of the company, SALT Software, in 2006.
What the future holds
All of these products, therapies, and companies still continue to evolve as research leads to new developments.
Zhang and BrainXell are currently working on getting approval from the Food and Drug Administration (FDA) for a clinical trial to test a new stem cell therapy in individuals with Parkinson’s Disease.
Opsis recently formed a $70 million strategic alliance with BlueRock Therapeutics in Boston and Bayer AG in Germany to take a treatment for retinitis pigmentosa into clinical trials, with cell therapies for macular degenerations on the horizon.
Transitioning Together is now working on how to make the program more accessible to different communities, testing its delivery through telehealth, and mechanisms on implementing it in locations with fewer resources. DaWalt also wants to expand the curriculum to be available for individuals with other intellectual and developmental disabilities.
SALT has continued to develop several new databases, collaborated with other countries, and produced different versions of SALT. The program is used in all 50 states and more than 20 countries in several languages. “Over the past 20 years we have produced countless versions of SALT, each one geared to a particular computer and each one easier to use than the last,” reads SALT Software’s website.
Wolff’s company, Mirus Bio, was bought by Roche in 2008 for $125 Million. Wolff passed away on April 17, 2020.
The desire and hard work to provide individuals with the best quality of care, and attend to needs with empirically tested and scientifically sound interventions distinguish scientists at the Waisman Center.
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Learn more about the Waisman Center's 50th Anniversary, including events, history, stories and images: 50 Years | 1973 - 2023 |