California Stem Cell Agency's 'Holiday' Awards: $25 Million for Research Ranging from Liver Failure to Dementia

OAKLAND, Ca. -- Directors of the California stem cell agency last week approved nearly $25 million for research but dashed the hopes of two scientists who were pushing extra hard for funding from the 13-year-old state enterprise.

Thirteen researchers ultimately received awards for tackling such afflictions as diabetes, dementia and liver failure. Thirty-two scientists who applied in the round were originally rejected by reviewers for the California Insitute for Regenerative Medicine, (CIRM), as the agency is formally known.

Reviewers make the de facto decisions on awards by the agency, although its governing board can override their actions. Four researchers whose proposals were nixed during an earlier, closed-door reviewer session sought to reverse those decisions.

Only two out of the four won over the board. One was Mark Tuszynski, director of the Translational Neuroscience Institute at UC San Diego, who sought $2.1 million to support his research to use neural stem cells to grow new connections through injured spinal cord. In a letter to the board prior to the meeting, he said ,

"As the present round of...funding winds down, this may be our last opportunity to develop this work to benefit the citizens of the state of California."

Tuszynski's application received a score of 80 out of 100, five points below the cutoff line of 85.

CIRM directors discussed the application briefly during which San Diego researcher addressed the board.

In addition to Tuszynski's application, the board reversed reviewers on an application for a cellular treatment for epilepsy. The $1.6 million proposal by Neurona Therapeutics of South San Francisco scored 80. Arnold Kriegstein, co-founder of the firm and head of the UC San Francisco stem cell program, spoke on behalf of the Neurona. 

The other appellants were Alice Tarantal of  UC Davis and Gregorio Chazenbalk of UCLA.

Tarantal filed a $1.1 million application (DISC2-10599) that she said involved "total-body positron emission tomography (PET) imaging technology, which currently is only available in California."

Her application was scored at 84 by reviewers, just one point below the cutoff line. Board members in the past have noted that such narrow differences are statistically meaningless.

Chazenbalk's $2.2 million application (DISC2-10473) involved a "new population of pluripotent stem cells" known as Muse cells, which he said can be used to treat acute myocardial infarction with a "high potential rate of success." His score was not disclosed but appears to be below 65.

Both Tarantal and Chazenbalk addressed the board but none of the directors discussed their applications. 

No discussion of the winning applications was conducted by the board members. A list of their names, institutions and projects is below.  

Here is the CIRM press release on the awards. It includes the application numbers for all proposals, which can be used to find the summaries of reviewer comments and scores. The specific review summaries can be found by scrolling more deeply into that document.

APPLICATION	TITLE	INSTITUTION	CIRM COMMITTED FUNDING
DISC2-10591	Preclinical development of an immune evasive islet cell replacement therapy for type 1 diabetes	ViaCyte	$1,470,987
DISC2-10524	Genome Editing of Sinusoidal Endothelial Stem Cells for Permanent Correction of Hemophilia A	Saswati Chatterjee City of Hope	$2,182,193
DISC2-10679	Towards hepatocyte cell replacement therapy: developing a renewable source of human hepatocytes from pluripotent stem cells	Irv Weismann Stanford	$2,201,136
DISC2-10748	Engineering Lifelong Cellular Immunity to HIV	Scott Kitchen U.C. Los Angeles	$1,701,178
DISC2-10714	iPS Glial Therapy for White Matter Stroke and Vascular Dementia	Stanley Thomas Carmichael U.C. Los Angeles	$2,096,095
DISC2-10604	Stimulating endogenous muscle stem cells to counter muscle atrophy	Helen Blau Stanford	$2,198,687
DISC2-10753	Generation and in vitro profiling of neural stem cell lines to predict in vivo efficacy for chronic cervical spinal cord injury.	Aileen Anderson U.C. Irvine	$1,575,613
DISC2-10751	Silicon Nanopore Membrane encapsulated enriched-Beta Clusters for Type 1 Diabetes treatment	Shuvo Roy U.C. San Francisco	$1,113,000
DISC2-10695	Identification and Generation of Long Term Repopulating Human Muscle Stem Cells from Human Pluripotent Stem Cells	April Pyle U.C. Los Angeles	$2,184,000
DISC2-10747	Targeting Cancer Stem Cells in Hematologic Malignancies	Tannishtha Reya U.C. San Diego	$2,167,200
DISC2-10559	Development of immune invisible beta cells as a cell therapy for type 1 diabetes through genetic modification of hESCs	Yang Xu U.C. San Diego	$2,167,200
DISC2-10525	Development of a cellular therapeutic for treatment of epilepsy	Neurona Therapeutics	$1,616,536
DISC2-10665	Neural Stem Cell Relays for Severe Spinal Cord Injury	Mark Tuszynski U.C. San Diego	$2,100,581

Chart by CIRM

Alpha Thalassemia to Strokes to Zika: A $64 Million Boost by California for Stem Cell Research

BURLINGAME, Ca. -- The California stem cell agency today awarded more than $64 million for research tackling cancer, stroke, leukemia, heart failure, brain injury, Zika and much, much more

The agency's directors allotted $44 million of the amount for two clinical trials and potentially two more trials, which are the last stages before approval of treatments for use by the general public. Prior to today's action, the agency -- known officially as the California Institute for Regenerative Medicine or CIRM -- was helping to finance 27 active clinical trials.

The agency has yet to develop therapies that would be available for widespread use that voters were led to expect in 2004 when they approved creation of the $3 billion research effort. CIRM expects to run out of cash for new awards in three years. 

The most advanced clinical research approved today involves a phase 2b trial for which CIRM ponied up $20 million. The effort is also backed with co-funding of $22 million by the recipient, SanBio, Inc., a Mountain View, Ca., subsidiary of a Japanese firm, SanBio Co., Ltd. 

The review summary of the application (CLIN2-10344) said the trial had already demonstrated safety and "a trend toward efficacy" involving ischemic strokes. The research is aimed at improving motor function of victims of strokes, which is the leading cause of adult disability.

Directors also approved $5.3 million for work aimed at starting a clinical trial for a treatment that would enhance the brain's ability to create new blood vessels to replace those damaged during a stroke. (The review summary for CLIN-09433 can be found here.)

The funds went to Gary Steinberg of Stanford University.

Maria Millan, interim president and CEO of the agency, said in a news release,

"Today the CIRM Board approved two very different methods, using different kinds of stem cells, to address this need. By funding 'multiple shots on goal' we believe that we have a better chance of finding a way to repair the damage caused by stroke and give people a better quality of life.”

The second phase 2 clinical trial backed by CIRM involves transplantation of maternal bone marrow stem cells into fetuses discovered to have alpha thalassemia major, an affliction that is almost always fatal in utero.

The $12.1 million award (CLIN2-09183) went to Tippi MacKenzie of UC San Francisco. (The review summary can be found here.)

The fourth application (CLIN1-09776) involves acute myeloid leukemia and preparation for a clinical trial application. CIRM awarded $6.9 million to Cellerant Therapeutics, Inc., of San Carlos. The agency reported that $1.7 million in co-funding would be provided by Cellerant. (The review summary can be found here.)

Also approved was $20 million for 13 awards in what the agency calls its Quest program, which is aimed at supporting promising, less developed research that is likely to move on to the next stage of development within two years. Twenty-six applications were rejected.

The review summaries and scores on the awards can be found in this document. The list of recipients can be found in the CIRM press release.

Conflict List for CIRM Directors on Quest Awards

Here is the conflict of interest list for directors of the California stem cell agency compiled by the agency in preparation for voting today on applications for Quest research awards. The list identifies the directors with conflicts on specific applications. The directors with conflicts are barred from voting on those applications or discussing them during today's meeting.

  Conflict of Interest List CIRM Directors Quest Awards June 2017 by DavidJensen on Scribd

Latest Targets of the California Stem Cell Agency: $26 Million for Zika, Heart Disease and Much More

The California stem cell agency next Thursday expects to award nearly $26 million to 14 scientists to seek therapies for afflictions ranging from cystic fibrosis to Zika.

The awards have all been approved by the agency's out-of-state reviewers in a round called "Quest." The $3 billion agency's board is scheduled to ratify reviewers' decisions at a telephonic meeting next week. The board almost never overturns its reviewers' decisions.

The expected outcome of a Quest award is "a candidate therapeutic, medical device, diagnostic or tool that is ready for translational stage activities."

The application receiving the highest score, 95, is seeking to develop "CRISPR/Cas9 mediated FOXP3 gene editing in patient-derived hematopoietic stem cells as a cure for IPEX syndrome."

The review summary on the $1.1 million proposal said,

"Using CRISPR/Cas9 gene editing, we will insert a wild type copy of the FOXP3 gene into patient derived HSCs, enabling pre-clinical proof of concept data for clinical trials that could reduce IPEX patient pathologies. This work will the first-in-man demonstration of the curative potential of edited HSCs and will help maintain California’s lead position in stem cell research and cure."

IPEX syndrome is a rare disease that can lead to diabetes and severe enlargement of secondary lymphoid organs.

The Zika award received the second highest score, 93. It is aimed at determining the "the impact of the Zika virus during human neurodevelopment and to test a FDA-approved therapeutic candidate to treat Zika infection." The research is budgeted for $2.1 million. 

The largest award, $2.4 million, is aimed at a gene therapy to "regenerate heart muscle for the 23 million adult and pediatric patients with heart failure, for whom there are currently no disease-modifying therapeutic approaches."  It received a score of 88.

The cystic fibrosis application was scored at 85, which was right at the cutoff line for funding. The proposal is aimed at "genome editing to correct cystic fibrosis mutations in airway  stem cells."  The application sought $2.2 million.

The reviews of 14 applications can be found here along with the reviews of unsuccessful applicants who scored from 84 to 65. None of the names of the applicants have been released yet by the agency, which withholds the information until after the board ratifies the reviewer decisions. 

Here is a link to the agenda for the meeting, which includes remote locations throughout the state at which the public can participate in the meeting and speak to the board. The meeting is also expected to be available through an audiocast. 

Remote locations include Oakland, San Diego, Napa, Irvine, Los Gatos, Elk Grove and San Francisco. Specific addresses can be found on the agenda.