Stories of hope and scientific progress in the CIRM Annual Report

This past year, CIRM scientists made significant progress toward new therapies. Several disease teams showed that their approach is likely to be effective and they are likely to be reaching clinical trials on target in the next few years. Other groups made progress in understanding how embryonic stem cells form adult cells and tissues and mimicking disease in a laboratory dish. CIRM formed new global partnerships to leverage world-wide stem cell expertise and seven of our major facilities opened their doors to stem cell scientists.

I know all this because it's in the just-published annual report. You can read the stories here, along with letters from Governing Board chair Robert Klein and President Alan Trounson.

My favorite part of every annual report is the focus on patient advocates and their stories. This year, we feature people living with (or caring for) those with amyotrophic lateral sclerosis (Lou Gehrig's disease), Huntington's disease, HIV/AIDS, epidermolysis bullosa and stroke, as well as a follow-up story on a woman living with a form of pre-leukemia who we featured in last year's report. She's doing well on a new therapy that came out of CIRM-funded research.

The patients and their stories keep CIRM scientists' focus where it belongs -- on developing new therapies for chronic disease and injury.

A.A.

Making neurons lose their inhibitions

CIRM grantees at Sanford-Burnham have just published an interesting paper in PLoS Biology about developing a type of neuron that could alleviate symptoms of Huntington's disease, autism, schizophrenia and bipolar disorder — all diseases in which some neurons lose their inhibitions.

First, the big picture. In the brain, some neurons send signals to other neurons, relaying information around the brain. Others simply act to dial up or down those signals. A group of neurons in a part of the brain called the basal ganglia serve to dial back signals from other parts of the brain, basically keeping the signals under control.

In some neurological diseases, it's the loss of those inhibitory neurons that allow signals to run rampant and cause symptoms. In which case, adding some new inhibitory neurons might be what it takes to control symptoms.

What postdoctoral fellow Christina Chatzi knew is that some inhibitory neurons rely on a molecule called retinoic acid in order to develop properly. Retinoic acid is a form of vitamin A that has long been known to aid in developing limbs and body patterning. Working in the lab of Gregg Duester, Chatzi wondered if exposing embryonic stem cells to retinoic acid could result in these inhibitory neurons. Turns out she was right.

Duester's lab studies the basic biology of the role of retinoic acid in development, but they say others may want to follow up on this work in attempt to develop therapies. Sanford-Burnham's excellent blog entry quotes Duester:

"But what we found here suggests that others could use retinoic acid to make inhibitory neurons to treat disease, just the way an embryo does it naturally."

This work is one great example of how basic biology can feed into the development of new therapies -- something we've blogged about before. Without a constant source of new ideas going into the research pipeline there will be no cures coming out the other end.

CIRM funds two awards to scientists working toward therapies involving inhibitory neurons derived from embryonic stem cells: A comprehensive award to Arnold Kriegstein at the University of California San Francisco, and an Early Translational II award to Arturo Alvarez-Buylla also at UCSF.

- A.A.

CIRM funding: Gregg Duester (RS1-00193)
PLoS Biology, April 12, 2011

Stem cell progress on brain awareness week

This week marks Brain Awareness Week, with events worldwide to bring people up to speed on brain research. I went to the cool search tool on the Dana Foundation web site and found that several CIRM grantees are hosting events this week. That makes sense, given that roughly a quarter of our funding goes to neuronal diseases. (You can see charts of CIRM stem cell research funding allocations here. The charts are slightly out of date — stay tuned for some updates in the next month.)

Brain diseases are seen as a big challenge for stem cell therapies, in part because the brain itself is such a complex web of neurons. Simply replacing a few lost neurons won't necessarily replicate the lost connections. We have a story discussing some of those issues and describint innovative approaches CIRM grantees are taking to developing new cures for brain diseases.

The good news is that some CIRM grantees are learning that stem cells can be coaxed to form the support cells in the brain that nourish neurons. These support cells could be what provide a therapy for diseases such as ALS, MS, stroke and spinal cord injury. Other grantees are using stem cells in the lab to test new drugs for Parkinson's disease.

A group at UC Davis is attempting to use the body's own mesenchymal stem cells to preserve unaffected neurons in people with Huntington's disease. This technique won't bring back lost cells, but saving additional cells from dying off could prevent some of the terrible side effects of the disease.

Another team of CIRM grantees at UC Irvine found that at least in rodents, stem cells were able to repair some memory loss due to Alzheimer's disease. This work is a long way from treating humans, but still provides hope for people who have lost loved ones to this devastating disease. Here's a video we produced about that work:



We've produced several other videos about CIRM's brain related research:

• Fred H. Gage talks about using embryonic stem cells to model neuronal disease
• Spinal Cord Injury: Progress and Promise in Stem Cell Research
• Huntington's Disease: Progress and Promise in Stem Cell Research
• Parkinson's Disease: Progress and Promise in Stem Cell Research
• Spotlight on ALS seminar
• Spotlight on Huntington's disease seminar
• Spotlight on Alzheimer's disease seminar
• Spotlight on Batten disease seminar
• Spotlight on Parkinson's disease seminar

 - A.A.

UC Davis scientist on a quest for cures in the cleanest of labs

Gerhard Bauer in the UC Davis GMP facility

One of the real thrills of working at CIRM is talking to the researchers who are so excited about finding new therapies. As part of our lunchtime talk series, today we heard from Gerhard Bauer of UC Davis. The only thing more exciting to Bauer than new therapies is the thought of having those therapies come out of his beautiful new GMP lab.

A GMP (Good Manufacturing Practice) lab is a clean facility that can be used to process the cells and other products that might one day go in people. When you see photos of scientists in white suits looking through microscopes, they’re likely in a GMP facility. If the lab sparkles so brightly you need sunglasses to look at the photos, it’s probably one of Bauer’s six GMP labs he’s built since moving from Austria to the U.S. in the 1980s to work on HIV/AIDS. He’s like the MacGyver of GMP labs. Nothing already manufactured was quite perfect enough for his facility, so in his spare time, you know, when he wasn’t running a lab and picking paint colors for the building, he also designed better GMP equipment.

Do I sound smitten? My apologies. I do aim for professional disinterest, but I am only human and I also really, really want to see therapies for some of the diseases they are tackling in that facility. It’s inspiring to see such enthusiasm in the people who are working toward those cures. Among the many diseases under investigation in the facility (Huntington’s disease, peripheral artery disease, bone fractures, liver disease) Bauer is part of the Stanford Disease Team working toward a therapy for the horrific childhood skin disorder epidermolysis bullosa. He and other members of that team recently spoke about the work at a governing board meeting. Videos of those talks are available here, but be warned that the disease is awful and the images are graphic. Personally, I can’t look.

One fun thing we learned is that Bauer has been taking on CIRM Bridges interns and training them in GMP procedures (here's a video about the Bridges program if you aren't familiar with it). He’s hired one, and has another working in the lab now. That’s exactly what we were hoping for in the Bridges program. Undergrad or masters students are learning stem cell science and getting trained for jobs in California’s expanding stem cell biology sector.

The lunch talks are a great opportunity for CIRM staff to hear about how those disease teams are progressing and to understand the challenges. Getting to a cure isn’t easy. One thing we all learned from Bauer’s talk is that whatever therapy the team comes up with, it’s going to be absolutely, totally, completely GMP certified. And clean? It’s going to be clean. Because when Bauer wasn’t dreaming up better lab equipment he was also certifying the cleaning protocols.

Here’s a video we made last year about the GMP facility:



- A.A.