Dr. Justin Ichida

CIRM & CZI & MOU for COVID-19

/ Kevin McCormack / Leave a comment

Too many acronyms? Not to worry. It is all perfectly clear in the news release we just sent out about this.

A new collaboration between the California Institute for Regenerative Medicine (CIRM) and the Chan Zuckerberg Initiative (CZI) will advance scientific efforts to respond to the COVID-19 pandemic by collaborating on disseminating single-cell research that scientists can use to better understand the SARS-CoV-2 virus and help develop treatments and cures.

CIRM and CZI have signed a Memorandum of Understanding (MOU) that will combine CIRM’s infrastructure and data collection and analysis tools with CZI’s technology expertise. It will enable CIRM researchers studying COVID-19 to easily share their data with the broader research community via CZI’s cellxgene tool, which allows scientists to explore and visualize measurements of how the virus impacts cell function at a single-cell level. CZI recently launched a new version of cellxgene and is supporting the single-cell biology community by sharing COVID-19 data, compiled by the global Human Cell Atlas effort and other related efforts, in an interactive and scalable way.

“We are pleased to be able to enter into this partnership with CZI,” said Dr. Maria T. Millan, CIRM’s President & CEO. “This MOU will allow us to leverage our respective investments in genomics science in the fight against COVID-19. CIRM has a long-standing commitment to generation and sharing of sequencing and genomic data from a wide variety of projects. That’s why we created the CIRM genomics award and invested in the Stem Cell Hub at the University of California, Santa Cruz, which will process the large complex datasets in this collaboration.”  

“Quickly sharing scientific data about COVID-19 is vital for researchers to build on each other’s work and accelerate progress towards understanding and treating a complex disease,” said CZI Single-Cell Biology Program Officer Jonah Cool. “We’re excited to partner with CIRM to help more researchers efficiently share and analyze single-cell data through CZI’s cellxgene platform.”

In March 2020, the CIRM Board approved $5 million in emergency funding to target COVID-19. To date, CIRM has funded 17 projects, some of which are studying how the SARS-CoV-2 virus impacts cell function at the single-cell level.

Three of CIRM’s early-stage COVID-19 research projects will plan to participate in this collaborative partnership by sharing data and analysis on cellxgene.   

  • Dr. Evan Snyder and his team at Sanford Burnham Prebys Medical Discovery Institute are using induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treating the virus.
  • Dr. Brigitte Gomperts at UCLA is studying a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19.
  • Dr. Justin Ichida at the University of Southern California is trying to determine if a drug called a kinase inhibitor can protect stem cells in the lungs and other organs, which the novel coronavirus selectively infects and kills.

“Cumulative data into how SARS-CoV-2 affects people is so powerful to fight the COVID-19 pandemic,” said Stephen Lin, PhD, the Senior CIRM Science Officer who helped develop the MOU. “We are grateful that the researchers are committed to sharing their genomic data with other researchers to help advance the field and improve our understanding of the virus.”

CZI also supports five distinct projects studying how COVID-19 progresses in patients at the level of individual cells and tissues. This work will generate some of the first single-cell biology datasets from donors infected by SARS-CoV-2 and provide critical insights into how the virus infects humans, which cell types are involved, and how the disease progresses. All data generated by these grants will quickly be made available to the scientific community via open access datasets and portals, including CZI’s cellxgene tool.

CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

/ Kevin McCormack / Leave a comment
Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

Scientists at USC untangle the mysteries of cellular reprogramming- a method that could be used to treat diseases

/ Yimy Villa / 1 Comment
Dr. Justin Ichida, Assistant Professor at USC and lead author of the study

Scientists have long tried to repurpose cells in order to potentially treat various types of conditions. This process, called reprogramming, involves changing one type of cell into another, such as a blood cell into a muscle cell or nerve cell. Although the technique has been around for decades, it has only been effective 1% of the time.

Fortunately, thanks in part to a CIRM grant, Dr. Justin Ichida and other researchers at USC have been able to untangle this complicated process to ensure reprogramming happens more efficiently. The researchers were able to figure out a process that reprograms cells much more reliably than previous methods.

USC scientists have found a solution to untangle twisty DNA, removing kinks so the molecules can be used to reprogram cells to advance regenerative medicine to treat disease.
Photo courtesy of Illustration/iStock

The technique the scientists developed uses an enzyme to untangle reprogramming DNA, similar to how a hairdresser conditions untangled hair. Since DNA molecules are twisty by nature, due to the double helix configuration, they do not respond well when manipulated to change itself. Therefore, reprogramming DNA requires uncoiling, yet when scientists begin to unravel the molecules, they knot up tighter.

“Think of it as a phone cord, which is coily to begin with, then gets more coils and knots when something is trying to harm it,” Dr. Ichida said in a press release by USC.

To smooth the kinks, the researchers treated cells with a chemical and genetic cocktail that activates enzymes that open up the DNA molecules. This process releases the coiled tension and lays out the DNA smoothly, leading to more efficient cellular reprogramming.

This new technique works almost 100% of the time and has been proven in human and mouse cells. The increased efficiency of this techniques opens the possibilities for studying disease development and drug treatments. New cells could be created to replace lost cells or acquire cells that can’t be extracted from people, a problem observed in Parkinson’s, ALS, and other neurological diseases.

Moreover, since these reprogrammed cells are the same age as the parent cell, they could be used to better understand age-related diseases. It is possible that the reprogrammed cells may be better at creating age-accurate models of human disease, which are useful to study a wide array of degenerative diseases and accelerated aging syndromes.

To summarize his work, Dr. Ichida states in the USC press release that,

“A modern approach for disease studies and regenerative medicine is to induce cells to switch their identity. This is called reprogramming, and it enables the attainment of inaccessible tissue types from diseased patients for examination, as well as the potential restoration of lost tissue. However, reprogramming is extremely inefficient, limiting its utility. In this study, we’ve identified the roadblock that prevents cells from switching their identity. It turns out to be tangles on the DNA within cells that form during the reprogramming process. By activating enzymes that untangle the DNA, we enable near 100% reprogramming efficiency.”

The full findings of this study can be found in Cell Stem Cell.