|Vanessa Lupian and her Mother Veronica discuss Vanessa's liver transplant|
Vanessa has maple syrup urine disease (MSUD), a metabolic liver disease caused by a genetic mutation. This inherited disorder leads to the lack of an enzyme responsible for digesting specific amino acids in foods like milk, meat, and eggs. The build up of amino acids can lead to the symptoms that haunted Vanessa. Her mother described Vanessa’s episodes:
When she would get sick we’d start seeing the side effects of her just not wanting to eat, the constant throwing up, and at times she’d even start hallucinating, not knowing who we were. All those points are very scary… From birth to 10 years, she was in the hospital one or two times a year. Three or four times we were close to losing her.Fortunately, Vanessa received a liver transplant in 2010. It wasn’t a cakewalk since she needed two transplants and four major surgeries over a 3-month period. But she is now doing well, going to school full time, and enjoys eating normal foods including her favorite: french fries. She was even able to donate her own liver to a child whose disease was not caused by MSUD. Still, Vanessa’s UCSF doctor, clinical fellow Andrew Grimm, pointed out to the board that:
The important thing to remember is that the therapies that we have for these [metabolic liver] diseases is pretty primitive. We understand the metabolic defects that are involved and so we can approach those from a biochemical perspective and can limit [certain foods]…but many children still have irreversible injury from metabolic [failure] so there’s a potential for cell therapies to be able to provide an alternative, less invasive, less dangerous method of treatment.The liver transplant helped Vanessa, but not everyone is as lucky. There are too few donated livers for all the people who need them, and organ transplants come at significant risk of rejection. With those limitations in mind, UCSF researcher Holger Willenbring has been trying to use stem cell-derived liver cells, or hepatocytes, as the tissue source for treating liver disease.
Willenbring spoke to the board about progress he’s making toward generating stem cell-derived liver cells for transplantation through collaborations with UC Davis and Shanghai Institute of Biological Sciences which are supported by CIRM Early Translation II and Early Translation III grants, respectively. He also points to his earlier CIRM SEED award as an important factor in helping him reach this point in his research:
I came to UCSF at the end of 2005, I was working on adult stem cells…I definitely didn’t have exposure to embryonic stem cells. And the CIRM SEED grant was definitely geared towards…people like me with a certain expertise with a certain desire to develop treatments to maybe consider…using and getting to know embryonic stem cells. I have since become a fan and a real believer of pluripotent stem cells and we have very little adult stem cell work going on in our lab. I’m not saying it’s not working or it’s not worth pursuing but … just simply because of the reason [that]…the [human] liver has 250 billion hepatocytes. It’s just a numbers game. It’s just about efficiency and just about making enough cells and I don’t know any adult stem that can pull it off. I’m grateful that I have an opportunity within my career to see this come to fruition and being applied in patients.You can bet that future patients like Vanessa who are suffering with liver disease and without many options will also be grateful.
This page shows all CIRM funding for liver disease.