Office of Science-Industry Partnerships
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 Acute Myeloid Leukemia
One-third of patients with acute myeloid leukemia (AML) don’t respond to chemotherapy, and the patients who do achieve remission are likely to relapse and fail further therapy. Dr. Michael Jensen is partnering with bluebird bio to pursue an innovative solution: the first potential T-cell immunotherapy for treating AML.
Our research collaboration with bluebird bio is intended to address two challenges of tackling AML, specifically the heterogeneity of the disease as well as the salvage of normal tissues with the potential for on-target/off-tumor targeting.
Seattle Children’s is a world leader in developing T-cell immunotherapies. Our approach is expected to leverage technology that enables T cells to target multiple antigens on the surface of cancer cells as well as bluebird’s proprietary Dimerizing Agent Regulated Immunoreceptor Complex (DARIC) platform. By utilizing the DARIC platform in potential product candidates, we expect to be able to exert pharmacologic control of CAR T cell activity in vivo, allowing the investigator to switch on and switch off the activity of the engineered T-cells in the patient as needed by administering a small molecule drug.
The research collaboration’s goal is to rapidly accelerate development of potential new therapies for patients with AML.
Bluebird’s financial contributions to research at Seattle Children’s could total more than $10 million over the course of this collaboration.
Fighting factor VIII inhibitors with mRNA
Dr. Carol Miao is partnering with Moderna to investigate whether messenger RNA (mRNA) therapy can be used to treat hemophilia A without the development of inhibitory antibodies.
The current treatment for hemophilia A patients is replacement therapy of factor 8 (FVIII) protein, which is costly and inconvenient. In addition, anti-FVIII antibodies are problematic because they can render factor replacement therapy ineffective.
Moderna is creating lipid nanoparticles (LNPs) that encapsulate mRNA encoding FVIII and other proteins, to treat hemophilia A safely and effectively, as both an on-demand and prophylactic treatment, and to prevent antibody responses.
This collaborative study investigates whether mRNA therapy can achieve therapeutic levels of FVIII as well as prevent anti-FVIII antibody formation in hemophilia A mice.
Investigating an Aptamer-Based Treatment for Sepsis
Dr. Adrian Piliponsky is collaborating with Aptahem to investigate an aptamer-based treatment for sepsis and other life-threatening inflammatory conditions. Sepsis is the world’s third largest cause of death, yet current treatment options are limited to antibiotics, IV fluids and adrenaline to control blood pressure.
Aptahem is taking a new approach. Their primary drug candidate, Apta-1, is being developed as an emergency drug to prevent organ and tissue damage caused by sepsis. Unlike current treatments, Apta-1 counteracts the wide spectrum of coagulation and inflammatory system reactions seen in sepsis patients.
Piliponsky and Aptahem are testing Apta-1 using cecal ligation and puncture (CLP)-induced sepsis models. They’ll also investigate how Apta-1 affects the secreting granulates of mast cells. Through these studies, Piliponsky and Aptahem aim to better understand the underlying mechanisms of Apta-1.
Investigating a Group B Streptococcus Vaccine for Pregnant Women
Dr. Lakshmi Rajagopal is collaborating with Minervax to study a Group B streptococcus (GBS) vaccine targeted to pregnant women. There’s a significant need for a GBS vaccine: At least 4 million maternal and infant GBS-related infections occur worldwide every year. GBS infection during pregnancy can lead to preterm delivery or stillbirth. And, in newborns, infection may result in sepsis, pneumonia or meningitis.
While IV antibiotics during labor can prevent infection during birth, there is currently no way to prevent infections in an unborn child. Using mouse models created in Rajagopal’s lab, she and Minervax are studying if the vaccine prevents GBS colonization and migration from the vagina to the uterus. This research could be a step toward clinical trials in pregnant women.
Developing Therapies to Prevent GBS Infection in Pregnant Women
Dr. Lakshmi Rajagopal is working with Nine to test a therapeutic intervention for preventing Group B streptococcus (GBS) infection in pregnant women and newborns.
GBS is commonly found in healthy women and typically doesn’t cause uterine infections. If GBS infects the uterus during pregnancy, it can increase the risk of preterm birth, stillbirths and early onset GBS infections. While antibiotics can be given before delivery, there is no effective therapy to prevent infections in utero.
Rajagopal has developed standardized mouse models to study intrauterine infections, using non-pregnant and pregnant mice. She and Nine are investigating whether a therapeutic intervention can prevent GBS from infecting the uterus in mouse models.
Investigating Oxytocin Therapies for Obesity
Dr. Christian Roth is partnering with OXT Therapeutics to investigate a novel oxytocin analogue as a weight-loss agent.
Research in obese animals and humans has shown that oxytocin reduces food intake and body weight. But it’s a suboptimal treatment because it’s metabolically unstable. To address this, OXT Therapeutics has developed an oxytocin analogue that offers enhanced stability and oxytocin receptor activity.
Roth previously identified a promising oxytocin analogue that reduced food intake and weight gain in lean rat models. Now he and OXT Therapeutics are investigating the therapeutic potential of another lead novel oxytocin analogue in obese models. The researchers aim to determine the minimum effective dose of the analogue, the range of doses that produce a therapeutic effect without adverse side effects, and the long-term efficacy.
The study is set up to provide a complete and detailed understanding of the mechanism of action of the newly-developed lead analogue and to provide the necessary justification for investigational new drug (IND) approval.
Investigating the Role of Cadherin in Disease
Dr. Barry Gumbiner is collaborating with Takeda to investigate cadherins in inflammatory disease. This research is a potential step toward clinical trials to determine whether mAbs to cadherin have potential as an effective therapy.
Searching for the Genes Behind Intractable Epilepsy
Unfortunately, many children with intractable epilepsy don’t respond to traditional treatments including standard medications or, in some instances, surgical resection. Dr. Ghayda Mirzaa and her colleagues are collaborating with UCB to conduct whole genome sequencing that could reveal more genes and pathways behind intractable epilepsy and open the door to novel treatments.
Mirzaa and her colleagues in the Center for Integrative Brain Research – including Dr. William Dobyns – have previously identified mutations that contribute to abnormal brain development and epilepsy. The UCB partnership builds on this progress. Initially, the collaboration focuses on sequencing brain tissue that is surgically removed from Seattle Children’s epilepsy patients and not required for standard neuropathology.
The sequencing is conducted at the Broad Institute, and the results are then analyzed by Dr. Mirzaa’s lab and UCB. The hope is that this will reveal new genes and mechanisms that contribute to epilepsy, and open the door to a broader collaboration that includes developing and testing novel treatments.
Developing Cell Therapies for Autoimmune Disease
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 for Rare Genetic Disorders
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.
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.