UPMC Enterprises Translational Sciences and the University of Pittsburgh Office of Innovation and Entrepreneurship are teaming on a second request for proposals for sponsored research projects in specific therapeutic areas. We are highlighting the two projects funded in the first RFP. We previously featured a project to develop a therapy for progressive supranuclear palsy (PSP), a debilitating neurodegenerative disease with no effective treatments. Now we feature a gene therapy from the lab of Dwi Kemaladewi, Assistant Professor of Pediatrics.
Children with congenital-onset muscular dystrophy carry faulty genes that manifest as progressive muscle wasting and declining neuromuscular function, for which there are no treatments available.
Dwi Kemaladewi, PhD, assistant professor of pediatrics, came to the University of Pittsburgh in 2019 from the University of Toronto to advance research into gene therapy to restore healthy muscle tissue in affected children.
The faulty gene, known as LAMA2, however, has more than 600 underlying mutations that have been identified in patients. Developing unique genetic fixes for all of them would be time and cost prohibitive. Therefore, Kemaladewi and her colleagues put their efforts into up-regulating LAMA1, a sister gene that is similar enough to LAMA2, and showed that they could reverse the effects of LAMA2 mutations in animal and patient-derived models using CRISPR activation.
They also developed a way to deliver the gene therapy, which had previously required two engineered viruses, or vectors, in a single vector. Delivering the therapy with a single vector will reduce potential toxicity of the treatment as well as the cost.
Kemaladewi and her team initially focused on showing the efficacy of the therapy before the severe symptoms developed. In humans, however, diagnosis of muscular dystrophy does not usually occur until several months after birth. They now turn to showing whether the LAMA1 therapy can help reverse nerve and muscle damages that have already occurred.
That’s where funding support from UPMC Enterprises comes into the picture. The Translational Sciences team at UPMC Enterprises, collaborated with the University Office of Innovation and Entrepreneurship, to issue a request for proposals for early-stage drug discovery research projects to solve unmet medical needs.
“With support from the UPMC Enterprises Translational Sciences group, we will be conducting experiments to mirror how a therapy would be used in patients,” Kemaladewi said.
Kemaladewi and her team are excited for the potential of their work and, importantly, for both the financial and commercialization support from UPMC Enterprises to be able to move closer to clinical trial.
“While we celebrate very recent successes of gene therapy in the treatment of muscular dystrophy, more innovation in this space is clearly needed – both to support patients suffering from rarer genetic forms of muscular dystrophy such as LAMA2-CMD, and to leverage emerging therapeutic technologies such as CRISPR-activation” said Matthias Kleinz, Executive Vice President of Translational Sciences at UPMC Enterprises. “Dr. Kemaladewi has dedicated her career to unraveling these rare muscular dystrophies, and to finding novel solutions that have the potential to restore patient mobility, independence, and quality of life. We are thrilled to support her mission to positively impact this under-served pediatric patient community.”
Pitt and UPMC Enterprises Translational Sciences are supporting a new funding opportunity for transformative therapeutics. Support of up to $1 million per year over two years is available. This request for proposals focuses on the following areas and awards are expected to be made later in 2023.
- Precision Cardiovascular Disease
- Precision Metabolic Disease
- Chronic Kidney Disease
- Next-Generation RNA Therapies