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:


ResearchBlogging.orgIsrael 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

6 thoughts on “Alzheimer’s disease in a dish provides hope, avenue to therapies

  1. We all know you guys like building models and buildings…but do you have any plans to help the patients?
    I know the ten year plan is to keep your salaries and benefits going but it be nice if you threw the patients a bone every now and then…no?

    Ontario's first cardiac stem cell transplant performed last week at the Peter Munk Cardiac Centre

    “This intraoperative approach to cardiac stem cell therapy is an important component of the new Organ Regeneration Laboratory at the University Health Network,” says Dr. Shaf Keshavjee, Surgeon-in-Chief at UHN. “Whether it is repairing hearts or lungs, the Organ Regeneration Laboratory is at the leading edge of regenerative medicine.”

    To date, over 500 heart patients worldwide have been treated with a variety of stem cell preparations. Eight patients have been treated at the Maisonneuve-Rosemont Hospital in Montreal as part of the IMPACT-CABG Clinical Trial. Toronto and Montreal researchers will merge their results after each centre performs stem cell transplants in 20 patients. The objective of the IMPACT-CABG Trial is to demonstrate the safety of injecting stem cells into the hearts of patients undergoing CABG surgery, and to gather information on the feasibility and efficacy of this approach.

    “This clinical trial marks an important milestone in regenerative medicine therapy at the University Health Network and paves the way for collaborative studies between scientists at the McEwen Centre and Dr. Yau and the team at the Peter Munk Cardiac Centre,” says Dr. Gordon Keller, Director of the McEwen Centre for Regenerative Medicine.

    Dr. Barry Rubin, Medical Director of the Peter Munk Cardiac Centre, commented, “The Peter Munk Cardiac Centre is leading innovation into new treatments for cardiovascular diseases. We are very pleased to partner with scientists in the McEwen Centre and to work together to provide novel stem cell therapies for our patients.”

  2. Hi,

    This is a very interesting trial. You might be aware that one of our grantees is also carrying out a stem cell-based trial in heart disease and has seen excellent results. You can read about his work here: We've also posted a video of this research speaking to our governing board here: It was a terrific talk and well worth watching.

    You might also want to see our list of awards that are for research that is in later stages of getting ready for clinical trial. We expect several of these to be in clinical trials in the next few years:

    In everything we do, we have the patients first and foremost in our minds. Remember that 10 members of our governing board–which is the body that votes on which awards we fund–serve on the board because they are disease advocates. For example, those advocates voted to support buildings because stem cell therapies will reach patients faster when the researchers have good equipment and resources. Those board members are themselves patients and are eager to see those new therapies realized.

  3. Cloning scientists create human brain cells

    Scientists in Edinburgh who pioneered cloning have made a technological breakthrough that could pave the way for better medical treatment of mental illnesses and nerve diseases

    “However, we have found a way round that. We can take a skin sample, make stem cells from it and then direct these stem cells to grow into brain cells. Essentially, we are turning a person's skin cells into brain. We are making cells that were previously inaccessible. And we could do that in future for the liver, the heart and other organs on which it is very difficult to carry out biopsies.”

    The scientists are concentrating on a range of neurological conditions, including multiple sclerosis, Parkinson's disease and motor neurone disease. In addition, work is being carried out on schizophrenia and bipolar depression, two debilitating ailments that are triggered by malfunctions in brain activity. This latter project is directed by Professor Andrew McIntosh of the Royal Edinburgh Hospital, who is working in collaboration with the regenerative medicine centre.

  4. Anonymous (first comment above),

    You nailed it with the salary and benefits comment! 80+% of research money goes to the same few individuals year after year that are doing the same old things that haven't worked in the past and won't work in the future. It's a perverse form of cronyism that stiffles new ideas from young researchers since the people that decide who gets the grants are the very researchers receiving the grants.

    BTW, a significant portion of CIRM (tax payer) money goes to research that doesn't even have a regenerative/stem cell component. It's basically just another very large pool of money for seasoned professors to exploit to further their own personal wealth (i.e. upgrade from Audi to Lexus).

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