We are partnering with private companies to rapidly develop treatments, devices and technologies that improve children’s lives. Our latest partnerships include:
Developing Cell Therapies for Autoimmune Disease
Drs. David Rawlings and Andrew Scharenberg
Seattle Children's Research Institute signed an exclusive licensing and collaboration agreement with Casebia Therapeutics to pursue novel therapeutic approaches for autoimmune disease.
The deal revolves around technologies – developed at Seattle Children’s by Drs. David Rawlings and Andrew Scharenberg – that use Casebia’s CRISPR/Cas9 technology to generate gene-edited regulatory T cells (Tregs). These gene-edited Tregs could eventually be used against a range of diseases such as immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome and other forms of autoimmunity.
Under the agreement, Casebia is sponsoring Rawlings’ research and collaborating with his lab in the continued development and application of gene-edited Tregs. In return, Casebia receives exclusive, worldwide rights to develop and commercialize certain intellectual property that results from the collaboration. Casebia’s funding contributions to Seattle Children’s could exceed $12 million over the course of the agreement.
Investigating mRNA Therapy
Dr. J. Lawrence Merritt, II is partnering with Moderna Therapeutics to investigate mRNA therapy for methylmalonic academia (MMA) and propionic acidemia (PA) – rare genetic disorders that disrupt amino acid metabolism and block production of enzymes that help digestion of certain proteins. Moderna has developed mRNA molecules that could restore protein expression in the liver and enable production of the missing enzymes.
As home to one of the West Coast’s largest biochemical genetics programs, Seattle Children’s sees a relatively large number of patients with MMA and PA. Dr. Merritt is collaborating with Moderna on an observational study to characterize the natural history of these patients. This is a step toward multicenter clinical trials to determine whether the mRNA approach can be an effective therapeutic option.
This therapeutic strategy could be extended to other diseases. With support from the Office of Science-Industry Partnerships, Seattle Children’s researchers are also collaborating with Moderna on additional projects in rare genetic disorders.
Creating a Cost-Effective Test for Drug-Resistant HIV
Dr. Lisa Frenkel is working with InBios International Inc. to manufacture an inexpensive, point-of-care assay that determines if patients have a drug-resistant strain of HIV prior to starting antiretroviral therapy (ART).
Pre-ART drug resistance is increasing in frequency across Africa, but there has been no rapid, cost-effective way to test for drug-resistant strains. Funding from the Office of Science-Industry Partnerships helped Frenkel develop an assay that overcomes this obstacle.
Frenkel’s assay predicts virologic failure of frontline ART and is rapid enough that testing can be completed before a patient leaves the clinic. This enables providers to match patients with the appropriate drug regimen – potentially preventing the spread of drug-resistant HIV strains.
Frenkel partnered with InBios and engineers at the University of Washington to translate the assay to freeze-dried reagents and to a paper strip test, and to develop a prototype test kit. Then Frenkel’s team validated the test – and proved it is easy to implement by staff with no technical expertise – at Coptic Hospital in Nairobi, Kenya. Negotiations are underway to manufacture the test for widespread distribution.
Identifying Biomarkers for Lupus
With systemic lupus erythematosus (SLE), a common clinical problem occurs when a patient develops a systemic febrile illness. The physician must then determine whether this is an infection, requiring antibiotic treatment, or a flare of SLE, requiring high-dose steroids or chemotherapy. Delayed treatment of either condition can be life-threatening.
Dr. Anne Stevens is working with NanoString Technologies to identify biomarkers that could lead to a relatively inexpensive, rapid screening test that directs real-time treatment for these critically vulnerable patients. The biomarkers could also be used to monitor disease activity.
Stevens and her colleagues are using NanoString technology to investigate gene expression in peripheral blood mononuclear cells from pediatric patients with SLE. The goal is to identify gene clusters that:
- Differentiate between infection and an SLE flare
- Predict gene flares
- Predict response to lupus medications
Once these gene clusters are identified, Stevens’ team will validate them with quantitative polymerase chain reaction. Her team then plans to translate their work into a point-of-care screening test.
Evaluating Biomarkers for Sepsis
Dr. Adrian Piliponsky is working with Immunexpress to identify and evaluate biomarkers for pediatric sepsis. Piliponsky has identified of a set of mast cell-related proteins that are potentially relevant to sepsis screening. Our initial work with Immunexpress built on Piliponsky’s findings by using a panel to identify a considerable number of candidate proteins that might have the dual function of being biomarkers for sepsis and affecting how mast cells respond to infection.
Now Piliponsky and Immunexpress are devising a screening strategy to narrow the list of candidate proteins and generate information relevant to research and commercial efforts, such as a sepsis screening test.