Alzheimer's disease in a dish provides hope, avenue to therapies

In Lawrence Goldstein’s lab at the new Sanford Consortium building in San Diego, a series of lab dishes hold cells that could unlock some of the mysteries of Alzheimer’s disease.

These cells are neurons made from the skin of people who have the disease. Goldstein and his team reprogrammed those skin cells into embryonic-like iPS cells, then matured those into nerve cells. The nerve cells in the dish show many of the same abnormalities scientists have come to recognize as hallmarks of the disease – higher levels of some proteins that form tangled masses and plaques in the brain.

The work was published today in Nature and is based on funding from CIRM awards to Goldstein and his co-authors Martin Marsala, Fred H. Gage and first author Mason Israel.

In the past, those tangles and plaques have only been seen in biopsies taken from people with the disease after they have died, providing a snapshot of the ravages caused by a lifetime of the disease. These cells and their unusual proteins in the lab dish represent the first time scientists have been able to study how the human nerve cells first start to go awry, and could provide clues to help guide new treatments for the disease. Currently there are no drugs to treat the estimated 30 million people worldwide who have the disease.

A story in Nature describes the work:

Scientists aiming to learn the causes of Alzheimer’s have looked to brain biopsies of patients after they die, blood tests and animals as diverse as fruitflies and fish. Until recently, it has not been possible to probe the neurons of Alzheimer’s patients before they show symptoms.

“By the time you can see dementia in a person, their brain cells have been behaving in an abnormal way for years, perhaps decades or longer,” says Larry Goldstein, a neuroscientist at the University of California, San Diego, who led the study published online today in Nature.

The group started with skin cells from four people with Alzheimer’s disease, two with the disease in their family and two who did not have the disease in their family. The idea is that the disease runs in families due to a single genetic change that makes the cells malfunction. The people who don’t have the disease in their family might have developed the disease due to genetic or environmental causes or other reasons. Having both sets of cells could allow the researchers to tease apart how the disease originates in people with known mutations versus through other causes.

These kinds of disease-in-a-dish studies have been carried out for a few different diseases in recent years, including schizophrenia, Parkinson’s disease and forms of autism, among others. In each case, one goal is to use the cells to test for drugs that can eradicate symptoms. If a drug can return an Alzheimer’s-like cell in a lab dish to a normal state, it might also help treat a person with the disease.

Nature writes:

But the hope is that such cells will help scientists to develop new drugs and match them to individual patients based on how their reprogrammed brain cells respond. Reprogrammed cells could even be used to diagnose people with Alzheimer’s decades before they show symptoms, Goldstein says. This would be of little use without proven therapies, but early diagnoses could help scientists select patients for clinical trials, he says.

“We’re in a terrible situation with a very common, devastating disease. It’s devastating financially and it’s devastating emotionally to the families who have to cope with it, and we have nothing to give patients that will work,” Goldstein says.

Finding a treatment for disabling conditions like Alzheimer’s disease was one of the driving reasons for the passage of proposition 71, which created CIRM. Leeza Gibbons has served on our board as a patient advocate for Alzheimer’s disease and is one of the patient advocate board members who help keep the board’s focus on therapies and patients who need them. Her mother had Alzheimer’s disease. She went on to found Leeza's Place to support the caregivers of people with Alzheimer's disease and other conditions.

CIRM has funded $11 million in awards focusing on Alzheimer’s disease. You can see a list of those awards here.

CIRM did a video with Fred Gage, one of the co-authors on this paper, talking about the use of stem cells in modeling diseases:


A.A.

Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, Carson CT, Laurent LC, Marsala M, Gage FH, Remes AM, Koo EH, & Goldstein LS (2012). Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature PMID: 22278060