Small state agencies like CIRM don’t normally get to partner with a behemoth like the Department of Defense (DOD), but these are not normal times. Far from it. That’s why we are both joining forces with the National Institutes of Health to fund a clinical trial that hopes to help patients on a ventilator battling a sometime fatal condition that attacks their lungs.
The study is being run by Dr. Michael Matthay from U.C. San Francisco. CIRM awarded Dr. Matthay $750,000 to help expand an existing trial and to partner with U.C. Davis to bring in more patients, particularly from underserved communities.
This approach uses mesenchymal stem cells (MSCs) taken from bone marrow to help patients with a condition called acute respiratory distress syndrome (ARDS). This occurs when the virus attacks the lungs.
In an article in UCSF News, Dr. Matthay says the impact can be devastating.
“Tiny air spaces in the lungs fill up with fluid and prevent normal oxygen uptake in the lungs. That’s why the patient has respiratory failure. Usually these patients have to be intubated and treated with a mechanical ventilator.”
Many patients don’t survive. Dr. Matthay estimates that as many as 60 percent of COVID-19 patients who get ARDS die.
This is a Phase 2 double blind clinical trial which means that half the 120 patients who are enrolled will get MSCs (which come from young, health donors) and the other half will get a placebo. Neither the patients getting treated nor the doctors and nurses treating them will know who gets what.
Interestingly this trial did not get started as a response to COVID-19. In fact, it’s the result of years of work by Dr. Matthay and his team hoping to see if MSC’s could help people who have ARDs as a result of trauma, bacterial or other infection. They first started treating patients earlier this year when most people still considered the coronavirus a distant threat.
“We started the study in January 2020, and then COVID-19 hit, so we have been enrolling patients over the last eight months. Most of the patients we’ve enrolled in the trial have ended up having severe viral pneumonia from COVID.”
So far CIRM has funded 17 different projects targeting COVID-19. You can read about those in our Press Release section.
One of the wonders of regenerative medicine is its broad applicability, which provides us with the opportunity to build upon existing knowledge and concepts. In the midst of a global pandemic, researchers have responded to the needs of patients severely afflicted with COVID-19 by repurposing existing therapies being developed to treat patients. The California Institute for Regenerative Medicine (CIRM) responded immediately to the pandemic and to researchers wanting to help by providing $5 million in emergency funding for COVID-19 related projects. In a short time span, this funding has driven innovation in the form of 17 new projects targeting COVID-19, many of which are based on previously developed concepts being repurposed to deal with the novel coronavirus.
One such example is a clinical trial funded by CIRM that uses natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, which are administered to patients with COVID-19. NK cells play an important role in defense against cancer and in fighting off viral infections. In fact, this exact same therapy was previously used in a clinical trial for patients with Acute Myeloid Leukemia, a type of blood cancer.
Another clinical trial funded by CIRM uses mesenchymal stromal cells (MSCs), a type of stem cell, to treat acute respiratory distress syndrome (ARDS), a life-threatening lung injury that occurs when fluid leaks into the lungs. As a result of ARDS, oxygen cannot get into the body and patients have difficulty breathing. ARDS is one of the most serious and lethal consequences of COVID-19, which is why this trial was expanded after the coronavirus pandemic to include COVID-19 positive patients.
Despite these great strides in driving innovation of therapies, one challenge that still needs to be tackled is providing patients access to these therapies, particularly people from underrepresented and underserved communities. In California alone, there have been over 621,000 positive cases as of August 2020, with more cases every day. However, the impact of the pandemic is disproportionately affecting the Latinx and African American communities more than others. An analysis by the Los Angeles Times found that the Latinx and African American communities have double the mortality rate from the coronavirus in Los Angeles County. Additionally, a surge in cases is being seen in poorer communities in comparison to wealthier ones.
Until a vaccine can be successfully developed and implemented to obtain herd immunity, the number of cases will continue to climb. There is also the challenge of the long term health effects of COVID-19, which can consist of neurological, breathing, and heart problems according to an article in Science. Unfortunately, a study published in the New England Journal of Medicine found that despite disproportionately higher rates of COVID-19 infection, hospitalization and death among people of color, they are significantly underrepresented in COVID-19 clinical trials.
The challenge of underrepresentation in clinical trials and research needs to be addressed by creating a more diverse population of study participants, so as to better generalize results to the U.S. population as a whole. CIRM Board Member Ysabel Duron, a leading figure in cancer education in the Latinx community, has advocated for more inclusion and outreach efforts directed towards underserved and underrepresented communities. By communicating with patients in underserved and underrepresented communities, building relationships established on a foundation of trust, and connecting patients with potential trial matches, underrepresentation can be alleviated.
To help in addressing these disparities, CIRM has taken action by changing the requirements for its discovery stage research projects, which promote promising new technologies that could be translated to enable broad use and improve patient care, and clinical trial stage projects.
For clinical trials, all proposals must include a written plan in the application for outreach and study participation by underserved and disproportionately affected populations. Priority will be given to projects with the highest quality plans in this regard. For discovery projects, all proposals must provide a statement describing how their overall study plan and design has considered the influence of race, ethnicity, sex and gender diversity. Additionally, all proposals should discuss the limitations, advantages, and/or challenges in developing a product or tools that addresses the unmet medical needs of California’s diverse population, including underserved communities. There is still much more work that needs to be done to address health disparities, but steps such as these can help steer progress in the right direction.
Driving innovation while addressing health disparities among people of color is just one of many opportunities and challenges of regenerative medicine in a post pandemic world. This blog post is part of Signal’s fifth annual blog carnival. Please click here to read what other bloggers think about this topic.
This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two new discovery research project as part of the $5 million in emergency funding for COVID-19 related projects. This brings the number of COVID-19 projects CIRM is supporting to 17, including three clinical trials.
$249,974 was awarded to Dr. Karen Christman at UC San Diego to develop a treatment for Acute Respiratory Distress Syndrome (ARDS), a life-threatening lung injury that occurs when fluid leaks into the lungs and is prevalent in COVID-19 patients. Dr. Christman and her team will develop extracellular matrix (ECM) hydrogels, a kind of structure that provides support to surrounding cells. The goal is to develop a treatment that can be delivered directly to site of injury, where the ECM would recruit stem cells, treat lung inflammation, and promote lung healing.
$250,000 was awarded to Dr. Lili Yang at UCLA to develop a treatment for COVID-19. Dr. Yang and her team will use blood stem cells to create invariant natural killer T (iNKT) cells, a powerful kind of immune cell with the potential to clear virus infection and mitigate harmful inflammation. The goal is to develop these iNKT cells as an off the shelf therapy to treat patients with COVID-19.
These awards are part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.
“The harmful lung inflammation caused by COVID-19 can be dangerous and life threatening,” says Maria T. Millan, M.D., the President and CEO of CIRM. “Early stage discovery projects like the ones approved today are vital in developing treatments for patients severely affected by the novel coronavirus.”
Earlier in the week the Board also approved changes to both DISC2 and clinical trial stage projects (CLIN2). These were in recognition of the Agency’s remaining budget and operational timeline and the need to launch the awards as quickly as possible.
For DISC2 awards the changes include:
Award limit of $250,000
Maximum award duration of 12 months
Initiate projects within 30 days of approval
All proposals must provide a statement describing how their overall study plan and design has considered the influence of race, ethnicity, sex and gender diversity.
All proposals should discuss the limitations, advantages, and/or challenges in developing a product or tools that addresses the unmet medical needs of California’s diverse population, including underserved communities.
Under the CLIN2 awards, to help projects carry out a clinical trial, the changes include:
Adjust award limit to the following:
Phase 1, Phase 1/2, Feasability Award Cap
Phase 2 Award Cap
Phase 3 Award Cap
Adjust the award duration to not exceed 3 years with award completion no later than November 2023
Initiate projects within 30 days of approval
All proposals must include a written plan in the application for outreach and study participation by underserved and disproportionately affected populations. Priority will be given to projects with the highest quality plans in this regard.
The changes outlined above for CLIN2 awards do not apply to sickle cell disease projects expected to be funded under the CIRM/NHLBI Cure Sickle Cell Disease joint Initiative.
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.”