22Q11 Deletion Syndrome

Stanford scientists link problems in nerve cells to schizophrenia

/ Yimy Villa / Leave a comment
A spherical cluster of hundreds of thousands of brain cells cultured in a lab dish. A team of researchers studied such neuronal clusters to better understand schizophrenia.
Image Credit: Pasca lab

The neurological origins of mental illness continue to remain a mystery and along with it any potential treatments for these conditions. However, Dr. Sergiu Pasca and his team at Stanford University have come one step closer to unlocking these mysteries for schizophrenia, a mental disorder characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. 

A common genetic defect called 22q11.2 deletion syndrome, or 22q11DS for short, has been linked to an astonishing 30-fold increased risk for developing schizophrenia. With help from CIRM funding, Dr. Pasca and his team have linked this genetic defect to an electrical defect in nerve cells.

To look at this more closely, the Stanford team generated tiny clusters of brain cells, called cortical spheroids which contain brain nerve cells, in a dish using skin cells from 22q11DS carriers and those from normal patients. The team then measured the resting membrane potential of these nerve cells, which is the voltage difference between the inner and outer part of the cell. This measurement is important because it keeps the nerve cells ready to fire while also preventing them from firing at random.

Dr. Pasca and his team found abnormal levels of resting membrane potential in nerve cells in the cortical spheroids made from 22q11DS carriers. They also found that the the 22q11DS-derived nerve cells spontaneously fired four times as frequently as nerve cells derived from normal patients. What’s even more promising is that the team found that treating the 22q11DS-derived nerve cells with any of three different antipsychotic drugs effectively reversed the defects in resting membrane potential and helped in prevent spontaneous firing.

Dr. Sergiu Pasca

In a press release, Dr. Pasca elaborated more on the team’s findings.

“We can’t test hallucinations in a dish. But the fact that the cellular malfunctions we identified in a dish were reversed by drugs that relieve symptoms in people with schizophrenia suggests that these cellular malfunctions could be related to the disorder’s behavioral manifestations.”

The full results of this study were published in Nature Medicine.

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

/ Kevin McCormack / 8 Comments

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

 Children’s Hospital of Los Angeles $1,297,512

 
DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

 Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

 U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

 Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

 University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

 Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

 Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

barbara_lee_official_photo

Congresswoman Barbara Lee (D-CA 13th District)

Congresswoman Barbara Lee (D-CA 13th DIstrict)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

 $93 million

$30 million
TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K