Two heads are better than one

SAN FRANCISCO—In 2004, California voters, through thepassage of the statewide ballot issue Proposition 71, overwhelmingly called forthe establishment of an entity to make grants and loans available for stem cellresearch. Seven years later, this entity—the California Institute forRegenerative Medicine (CIRM)—has been called the world's largest backer of stemcell research, and with a recently signed agreement, the CIRM is nowcollaborating with perhaps the largest sponsor of research funding in theworld: the U.S. National Institutes of Health (NIH).

A memorandum of understanding announced at the end of Octoberand signed by CIRM President Alan Trounson and NIH Deputy Director forIntramural Research Michael Gottesman has established a framework to advancethe parties' "complementary and synergistic goals," and to "help NIH and CIRMresearchers work together to bring their special talents in stem cell andregenerative medicine research to bear upon prevention, diagnosis and treatmentof various diseases."

"The goal is to use this agreement as a springboard tocreate synergy between our funding streams and expand the capacity of eachagency to move advances in basic research more rapidly into the clinic," saidDr. Mahendra Rao, director of the NIH Center for Regenerative Medicine, in astatement.

It was the appointment of Rao that "allowed us to get thisagreement done efficiently," says Trounson.

"We're very pleased to be able to work with what is clearlythe strongest research agency in the world, and broadly across many areas ofmedicine," Trounson says. "This partnership joins our strengths in stem cellsand regenerative medicine with their broad medicine capabilities."

Since its inception, the CIRM has used bond proceeds to fundbasic and applied biomedical research focused on developing diagnostics andtherapies, and on other vital research opportunities that it believes will leadto life-saving medical treatments. All proposals are peer-reviewed to supportthe most promising scientific research. Research grants are made only toCalifornia-based research institutions.

"In the beginning, we established the infrastructure that iscreating the training grounds and scientists other areas to join in stem cellresearch being conducted in California—scientists who already had track recordsin stem cell research," Trounson explains. "We then added a facility, and laterbuilt 12 new research institutes in California. We have allocated more than $1billion to these institutes, and all but two are open."

Funding research involving all types of stem cells, theCIRM's projects focus on specific disease therapies with the end goal ofgenerating proof-of-concept for their therapeutic approach, finding a candidatedrug or cell type to be developed into a therapy or filing an investigation newdrug (IND) application with the U.S. Food and Drug Administration to begin clinicaltrials. In future years, the agency will fund increasing amounts of new therapydevelopment in different diseases. The CIRM spreads its funding around to awide variety of disease areas, including blood/immune disorders, bone/cartilagedisorders, cancer, endocrine disorders/diabetes, cardiovascular disease,gastrointestinal/liver disease, muscular disorders, nervous systemdisorders/injuries, sensory organ disorders and reproductive disorders.

"There is a sort of very sharp front edge to the work. Some ofthe studies are progressing very quickly, while others are still making theirway through the pipeline," Trounson says.

But the CIRM "has always been interested in linking up withfederal agencies—and the NIH funds a lot of work in the area of stem cellresearch," Trounson notes.

Specifically, the agency will work with the NIH through itstrans-NIH Center for Regenerative Medicine (NIH CRM), the newly established NIHCenter for Translational Therapeutics (NCTT) and the NIH Clinical Center. Thelatter, the world's largest hospital dedicated entirely to clinical research,is what the CIRM found most attractive, says Trounson. The center houses basic,translational and clinical research efforts of the NIH intramural researchcommunity.

"They have the largest facility focused on clinical trialsin the United States, maybe the world," he says. "They have a fantastic programthere, and it's something I wouldn't really try to replicate in California, butthought that getting access to the clinical center would be great. We thoughtit would be useful to utilize resources that are already available, notduplicate them."

There are several opportunities for collaboration betweenthe two parties. The first

relates to the current round of applications for CIRM's DiseaseTeam Therapy Development Research awards. During the planning phase of theseawards, California teams could develop collaborations with researchers at theNIH Clinical Center on various aspects of a preclinical, Phase I, Phase I/II orPhase II clinical trial.

Another option is to give California researchers theopportunity to take part in NIH Clinical Center visiting fellowship or clinicalinvestigator training programs. Finally, CIRM institutions may be given accessto unique resources that may not be available at their home institution.

In addition to translational and clinical projects, the twogroups are exploring ways for the CIRM and NIH scientists to collaborate inearlier translational or basic biology projects.

"It takes time to get through the clinical trials process,so you can demonstrate in humans how cell products or regenerative medicine isgoing to work," Trounson concludes. "On the other hand, I remain veryoptimistic that this is going to be a big game-changer in modern medicine."