Alzheimer’s disease

Two common viruses could trigger Alzheimer’s disease

/ Katie Sharify / Leave a comment

Researchers from Tufts University and the University of Oxford have found that two common viruses —the varicella zoster and herpes simplex viruses— could trigger Alzheimer’s disease.

Varicella zoster (VZV) is an extremely common virus causes which causes chickenpox. Once cured of the first infection, the virus tends to linger in peripheral nerves where they remain dormant. When these dormant viruses are reactivated, they cause shingles.

HSV-1, the subtype of the herpes simplex virus, causes both oral and genital herpes. It is a very common infection, affecting nearly 4 million people worldwide under the age of 50 years. The American Sexual Health Organization estimates that around one in two adults has oral herpes in the United States. 

Cytokines are produced in response to VZV. Cytokines are part of a healthy immune system. These small proteins help control the growth and activity of your blood cells and immune cells. Cytokines tell your immune system to do its job. But when too many cytokines are released, it can cause your immune system to go into overdrive, resulting in cytokine storm.

In their findings, published in the Journal of Alzheimer’s Disease, researchers found that when VZV infect neurons, they trigger an inflammatory response due to this overproduction of cytokines. This inflammatory response in turn awakens the herpes simplex viruses which typically lie dormant and harmless in the brain. With both viruses now active, inflammation throughout the brain is aggravated, potentially leading to the formation of plaque and the slow deterioration of neurons—both hallmarks of Alzheimer’s.

The study’s leading author, Dana Cairns, along with her team of collaborators gathered data by using lab grown cultures of brain nerve, or neural, stem cells. They found that infecting neurons with varicella zoster alone was not enough to trigger Alzheimer-like properties. However, when the herpes simplex was already lying-in wait, varicella zoster initiated a series of events that resulted in plaques, tangled fibers and brain damage.

“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” explains Cairns. One of her collaborators, Oxford’s Ruth Itzhaki, was one of the first scientists to suggest a link between herpes infections and Alzheimer’s.

The California Institute for Regenerative Medicine (CIRM) has already invested almost $35 million in 21 different Alzheimer’s projects. In addition, we are committed to investing at least $1.5 billion in treatments that target conditions affecting the brain and central nervous system (CNS), including Alzheimer’s. 

Study reveals new evidence of key mechanism in Alzheimer’s

/ Esteban Cortez / 1 Comment

In California, 690,000 people aged 65 and older are living with Alzheimer’s, a degenerative brain disease and the most common form of dementia. In the United States, 5.8 million people aged 65 and older live with Alzheimer’s disease. Alzheimer’s affects memory, thinking and behavior and symptoms eventually grow in severity to interfere with daily tasks.  

There is no cure for Alzheimer’s, which is why Rutgers scientists are examining human brain cells in mice to identify a pivotal mechanism that could result in a potential therapy for the disease. In a recent study, the Rutgers team found more clear-cut evidence of how the destructive proteins linked to Alzheimer’s disease attack human brain cells and destroy surrounding tissue. 

The researchers studied human brain immune cells injected into the brains of specially bred immunodeficient mice, creating what they called a human-mouse chimera. The researchers detailed what happened to specialized immune brain cells known as microglia after those cells were exposed to tau proteins—destructive substances believed to be involved in Alzheimer’s and other severe human brain diseases. 

“This provided an unprecedented opportunity to investigate the role of human microglia in brains as well as the cognitive impairment seen in Alzheimer’s Disease and Down syndrome, a genetic disorder with a high risk of developing Alzheimer’s disease,” said Peng Jiang, an associate professor in the Department of Cell Biology and Neuroscience at the Rutgers School of Arts and Sciences. 

By studying the process in the newly-developed brain—which allowed human cells to grow, develop and mature with appropriate functions—the scientists were able to witness and analyze a cellular brain attack that has been largely elusive up to this point. 

In autopsies, scientists have been able to study the brains of people who died from Alzheimer’s and have seen residues of tau proteins and cellular changes. The human-mouse brain chimera has allowed the Rutgers team to extract and see human cells in the actual process of deterioration. 

The mice in the study were specially bred to be immunodeficient so that they could receive implanted human cells without rejecting them due to normal immune defenses.  The immunodeficient mice were injected with human microglial cells and, later, with tau proteins, which are linked to the development of the brain disease. 

“Since microglial cells are one of the first cell responders when something goes wrong in the brain, we believe the changes we saw to be significant,” said Mengmeng Jin, a postdoctoral researcher in the Department of Cell Biology and Neuroscience at Rutgers and first author on the study. 

The California Institute for Regenerative Medicine (CIRM) is committed to investing at least $1.5 billion—more than double what CIRM funded between 2006 and 2020—in treatments that target conditions affecting the brain and central nervous system (CNS), including Alzheimer’s. 

Read the source release about the study here.  

Replacement brain cells offer hope for Parkinson’s treatment

/ Kevin McCormack / 1 Comment
A colony of iPSCs from a Parkinson’s patient (left) and dopaminergic neurons made from these iPSCs (right) to model PD. (Image credit: Jeanne Loring)

A new study that used adult blood stem cells to create replacement brain nerve cells appears to help rats with Parkinson’s.

In Parkinson’s, the disease attacks brain nerve cells that produce a chemical called dopamine. The lack of dopamine produces a variety of symptoms including physical tremors, depression, anxiety, insomnia and memory problems. There is no cure and while there are some effective treatments they tend to wear off over time.

In this study, researchers at Arizona State University took blood cells from humans and, using the iPSC method, changed those into dopamine-producing neurons. They then cultured those cells in the lab before implanting them in the brains of rats which had Parkinson’s-like symptoms.

They found that rats given cells that had been cultured in the lab for 17 days survived in greater numbers and seemed to be better at growing new connections in their brains, compared to rats given cells that had been cultured for 24 or 37 days.

In addition, those rats given larger doses of the cells experienced a complete reversal of their symptoms, compared to rats given smaller doses.

In a news release, study co-author Dr. Jeffrey Kordower, said: “We cannot be more excited by the opportunity to help individuals who suffer from [a] genetic form of Parkinson’s disease, but the lessons learned from this trial will also directly impact patients who suffer from sporadic, or non-genetic forms of this disease.”

The study, published in the journal npj Regenerative Medicine, says this approach might also help people suffering from other neurological diseases like Alzheimer’s or Huntington’s disease.

How some brilliant research may have uncovered a potential therapy for Alzheimer’s 

/ Kevin McCormack / Leave a comment
Dr. Nicole Koutsodendris, photo courtesy Gladstone Institutes

In the world of scientific research, the people doing clinical trials tend to suck up all the oxygen in the room. They’re the stars, the ones who are bringing potential therapies to patients. However, there’s another group of researchers who toil away in the background, but who are equally deserving of praise and gratitude. 

Dr. Lana Zholudeva, photo courtesy Gladstone Institutes

These are the scientists who do basic or discovery-level research. This is where all great therapies start. This is where a researcher gets an idea and tests it to see if it holds promise. A good idea and a scientist who asks a simple question, “I wonder if…..”  

Dr. Yadong Huang, Photo courtesy Gladstone Institutes

In our latest “Talking ‘Bout (re)Generation” podcast we talk to three researchers who are asking those questions and getting some truly encouraging answers. They are scientists at the Gladstone Institutes in San Francisco: one seasoned scientist and two young post-docs trying to make a name for themselves. And they might just have discovered a therapy that could help people battling Alzheimer’s disease. 

Enjoy the podcast.

  

Raising awareness about mental health

/ Kevin McCormack / Leave a comment

THIS BLOG IS ALSO AVAILABLE AS AN AUDIOCAST ON SPOTIFY

World Mental Health Day is observed on 10 October every year. It’s a time to try and raise awareness about mental health issues and the impact they have not just on the individual but their family, their community and all of us. The theme for World Mental Health Day 2021 is ‘mental health in an unequal world.’

Dr. Le Ondra Clark Harvey: Photo courtesy CCCBHA

To highlight the issues raised on World Mental Health Day we talked to one of CIRM’s newest Board member, Dr. Le Ondra Clark Harvey. She’s a psychologist and the CEO of the California Council of Community Behavioral Health Agencies (CCCBHA) a statewide advocacy organization representing mental health and substance use disorder non-profit agencies that collectively serve over 750 thousand Californians annually.

What made you want to be on the CIRM Board?

I was recommended to apply for the CIRM Board by a member of CCCBHA, the organization I am privileged to lead and serve. I saw the position as an opportunity to shed light on cognitive disorders that many do not readily think of when they think about stem cell research. The appointment also has personal meaning to me as I have a grandfather who is a cancer survivor and  who has an Alzheimer’s diagnosis.  Breast cancer has also affected women in my family, including myself, and I know that the research that CIRM funds can assist with finding a cure and providing accessible treatment options for all Californians. 

A lot of people might not think that stem cells would have a role in addressing mental health issues, what role do you think they can play?

You are correct, most people do not immediately think of stem cell therapies as a remedy to brain health disorders. However, there are many cognitive disorders and symptoms that can be mitigated, and hopefully someday ameliorated, as a result of stem cell therapies. For example, autism and other developmental disabilities, dementia, Alzheimer’s, Tourette’s and tardive dyskinesia.  

What are the biggest challenges we face in addressing mental health issues in this country?

Stigma remains a significant barrier that impacts the ability to provide – particularly among racially and ethnically diverse communities. In my own practice, I’ve seen how stigma can prevent individuals from entering into care even when access issues have been mitigated. Public awareness campaigns, and culturally specific advocacy efforts and practices must be integrated into treatment models in order to provide individuals with the specific care they need. 

Do you think that the widespread media attention paid to Naomi Osaka and Simone Biles has helped raise awareness about mental health and perhaps also reduced some of the stigma surrounding it?

Yes, I do. Also, the pandemic has opened many individuals eyes, and engendered a sense of empathy, about the prevalence and impact that isolation and loneliness can have on a person. 

Lack of diversity impacts research into Alzheimer’s and dementia

/ Kevin McCormack / Leave a comment

THIS BLOT IS ALSO AVAILABLE AS AN AUDIOCAST ON SPOTIFY

A National Institutes of Allergy and Infectious Diseases clinical trial admissions coordinator collects information from a volunteer to create a medical record. Credit: NIAID

Alzheimer’s research has been in the news a lot lately, and not for the right reasons. The controversial decision by the Food and Drug Administration (FDA) to approve the drug Aduhelm left many people wondering how, when, or even if it should be used on people battling Alzheimer’s disease. Now a new study is raising questions about many of the clinical trials used to test medications like Aduhelm.

The research, published in the journal Jama Neurology, looked at 302 studies on dementia published in 2018 and 2019. Most of these studies were carried out in North America or Europe, and almost 90 percent of those studied were white.

In an accompanying editorial in the journal, Dr. Cerise Elliott, PhD, of the National Institute on Aging (NIA) in Bethesda, Maryland, and co-authors wrote that this limited the value of the studies: “This, combined with the fact that only 22% of the studies they analyzed even reported on race and ethnicity, and of those, a median 89% of participants were white, reflects the fact that recruitment for research participation is challenging; however, it is unacceptable that studies continue to fail to report participant demographics and that publishers allow such omissions.”

That bias is made all the more glaring by the fact that recent data from the Centers for Disease Control and Prevention shows that among people 65 and older, the Black community has the highest prevalence of Alzheimer’s disease and related dementias (13.8%), followed by Latinx (12.2%), non-Hispanic white (10.3%), American Indian and Alaskan Native (9.1%), and Asian and Pacific Islander (8.4%) populations.

The researchers admitted that the limited sample size – more than 40 percent of the studies they looked at included fewer than 50 patients – could have impacted their findings. Even so this clearly suggests there is a huge divide between the people at greatest risk of developing Alzheimer’s, or some other form of dementia, and the people being studied.

In the editorial, Elliott and his colleagues wrote that without a more diverse and balanced patient population this kind of research: “will continue to underrepresent people most affected by the disease and perpetuate systems that exclude important valuable knowledge about the disease.”


There are more details on this in Medpage Today.

An editorial in the New England Journal of Medicine highlights how this kind of bias is all too common in medical research.

“For years, the Journal has published studies that simply do not include enough participants from the racial and ethnic groups that are disproportionately affected by the illnesses being studied to support any conclusions about their treatment. In the United States, for example, Black Americans have high rates of hypertension and chronic kidney disease, Hispanic Americans have the highest prevalence of nonalcoholic fatty liver disease, Native Americans are disproportionately likely to have metabolic syndrome, and Asian Americans are at particular risk for hepatitis B infection and subsequent cirrhosis, but these groups are frequently underrepresented in clinical trials and cohort studies.”

“For too long, we have tolerated conditions that actively exclude groups from critical resources in health care delivery, research, and education. This exclusion has tragic consequences and undermines confidence in the institutions and the people who are conducting biomedical research. And clinicians cannot know how to optimally prevent and treat disease in members of communities that have not been studied.”

The encouraging news is that, finally, people are recognizing the problem and trying to come up with ways to correct it. The not so encouraging is that it took a pandemic to get us to pay attention.

At CIRM we are committed to being part of the solution. We are now requiring everyone who applies to us for funding to have a written plan on Diversity, Equity and Inclusion, laying out how their work will reflect the diversity of California. We know this will be challenging for all of us. But the alternative, doing nothing, is no longer acceptable.

Paving the way for a treatment for dementia

/ Kevin McCormack / Leave a comment
What happens in a stroke

When someone has a stroke, the blood flow to the brain is blocked. This kills some nerve cells and injures others. The damaged nerve cells are unable to communicate with other cells, which often results in people having impaired speech or movement.

While ischemic and hemorrhagic strokes affect large blood vessels and usually produce recognizable symptoms there’s another kind of stroke that is virtually silent. A ‘white’ stroke occurs in blood vessels so tiny that the impact may not be noticed. But over time that damage can accumulate and lead to a form of dementia and even speed up the progression of Alzheimer’s disease.

Now Dr. Tom Carmichael and his team at the David Geffen School of Medicine at UCLA have developed a potential treatment for this, using stem cells that may help repair the damage caused by a white stroke. This was part of a CIRM-funded study (DISC2-12169 – $250,000).

Instead of trying to directly repair the damaged neurons, the brain nerve cells affected by a stroke, they are creating support cells called astrocytes, to help stimulate the body’s own repair mechanisms.

In a news release, Dr. Irene Llorente, the study’s first author, says these astrocytes play an important role in the brain.

“These cells accomplish many tasks in repairing the brain. We wanted to replace the cells that we knew were lost, but along the way, we learned that these astrocytes also help in other ways.”

The researchers took skin tissue and, using the iPSC method (which enables researchers to turn cells into any other kind of cell in the body) turned it into astrocytes. They then boosted the ability of these astrocytes to produce chemical signals that can stimulate healing among the cells damaged by the stroke.

These astrocytes were then not only able to help repair some of the damaged neurons, enabling them to once again communicate with other neurons, but they also helped another kind of brain cell called oligodendrocyte progenitor cells or OPCs. These cells help make a protective sheath around axons, which transmit electrical signals between brain cells. The new astrocytes stimulated the OPCs into repairing the protective sheath around the axons.

Mice who had these astrocytes implanted in them showed improved memory and motor skills within four months of the treatment.  

And now the team have taken this approach one step further. They have developed a method of growing these astrocytes in large amounts, at very high quality, in a relatively short time. The importance of that is it means they can produce the number of cells needed to treat a person.

“We can produce the astrocytes in 35 days,” Llorente says. “This process allows rapid, efficient, reliable and clinically viable production of our therapeutic product.”

The next step is to chat with the Food and Drug Administration (FDA) to see what else they’ll need to do to show they are ready for a clinical trial.

The study is published in the journal Stem Cell Research.

Hollywood and Patient Advocacy – two people who are on our Board but never boring

/ Kevin McCormack / Leave a comment

At first glance Lauren Miller Rogen and Dr. David Higgins seem an unlikely pair. She’s an actor, writer, director and has worked with some of the biggest names in Hollywood. He has a doctorate in molecular biology and genetics and has worked at some of the most well-known companies in biotech. But together they make a great team.

Lauren and David are both on the CIRM Board. She’s a patient advocate for Alzheimer’s and the driving force (with her husband Seth) of HFC (Hilarity for Charity), which has raised millions of dollars to help families battling the disease and to educate young people about the condition. It’s also made a lot of people laugh along the way. David is a patient advocate for Parkinson’s and has been instrumental is creating support groups that help patients and families cope with the disease.

Together they are a force for good. And they’re also really funny. And that’s why we invited them to be guests on the CIRM Podcast, Talking ‘Bout (re)Generation. They are smart, engaging, witty, and they don’t pull punches.

I know you are going to enjoy the show.

/ Kevin McCormack / 1 Comment

Two voices, one message, watch out for predatory stem cell clinics

Last week two new papers came out echoing each other about the dangers of bogus “therapies” being offered by predatory stem cell clinics and the risks they pose to patients.

The first was from the Pew Charitable Trusts entitled: ‘Harms Linked to Unapproved Stem Cell Interventions Highlight Need for Greater FDA Enforcement’ with a subtitle: ‘Unproven regenerative medical products have led to infections, disabilities, and deaths.’

That pretty much says everything you need to know about the report, and in pretty stark terms; need for greater FDA enforcement and infections, disabilities and deaths.

Just two days later, as if in response to the call for greater enforcement, the Food and Drug Administration (FDA) came out with its own paper titled: ‘Important Patient and Consumer Information About Regenerative Medicine Therapies.’ Like the Pew report the FDA’s paper highlighted the dangers of unproven and unapproved “therapies” saying it “has received reports of blindness, tumor formation, infections, and more… due to the use of these unapproved products.”

The FDA runs down a list of diseases and conditions that predatory clinics claim they can cure without any evidence that what they offer is even safe, let alone effective. It says Regenerative Medicine therapies have not been approved for the treatment of:

  • Arthritis, osteoarthritis, rheumatism, hip pain, knee pain or shoulder pain.
  • Blindness or vision loss, autism, chronic pain or fatigue.
  • Neurological conditions like Alzheimer’s and Parkinson’s.
  • Heart disease, lung disease or stroke.

The FDA says it has warned clinics offering these “therapies” to stop or face the risk of legal action, and it warns consumers: “Please know that if you are being charged for these products or offered these products outside of a clinical trial, you are likely being deceived and offered a product illegally.”

It tells consumers if you are offered one of these therapies – often at great personal cost running into the thousands, even tens of thousands of dollars – you should contact the FDA at ocod@fda.hhs.gov.

The Pew report highlights just how dangerous these “therapies” are for patients. They did a deep dive into health records and found that between 2004 and September 2020 there were more than 360 reported cases of patients experiencing serious side effects from a clinic that offered unproven and unapproved stem cell procedures.

Those side effects include 20 deaths as well as serious and even lifelong disabilities such as:

  • Partial or complete blindness (9).
  • Paraplegia (1).
  • Pulmonary embolism (6).
  • Heart attack (5).
  • Tumors, lesions, or other growths (16).
  • Organ damage or failure in several cases that resulted in death.

More than one hundred of the patients identified had to be hospitalized.

The most common type of procedures these patients were given were stem cells taken from their own body and then injected into their eye, spine, hip, shoulder, or knee. The second most common was stem cells from a donor that were then injected.

The Pew report cites the case of one California-based stem cell company that sold products manufactured without proper safety measures, “including a failure to properly screen for communicable diseases such as HIV and hepatitis B and C.” Those products led to at least 13 people being hospitalized due to serious bacterial infection in Texas, Arizona, Kansas, and Florida.

Shocking as these statistics are, the report says this is probably a gross under count of actual harm caused by the bogus clinics. It says the clinics themselves rarely report adverse events and many patients don’t report them either, unless they are so serious that they require medical intervention.

The Pew report concludes by saying the FDA needs more resources so it can more effectively act against these clinics and shut them down when necessary. It says the agency needs to encourage doctors and patients to report any unexpected side effects, saying: “devising effective strategies to collect more real-world evidence of harm can help the agency in its efforts to curb the growth of this unregulated market and ensure that the regenerative medicine field develops into one that clinicians and patients can trust and safely access.”

We completely support both reports and will continue to work with the FDA and anyone else opposed to these predatory clinics. You can read more here about what we have been doing to oppose these clinics, and here is information that will help inform your decision if you are thinking about taking part in a stem cell clinical trial but are not sure if it’s a legitimate one.

Meet the people who are changing the future

/ Kevin McCormack / 2 Comments
Kristin MacDonald

Every so often you hear a story and your first reaction is “oh, I have to share this with someone, anyone, everyone.” That’s what happened to me the other day.

I was talking with Kristin MacDonald, an amazing woman, a fierce patient advocate and someone who took part in a CIRM-funded clinical trial to treat retinitis pigmentosa (RP). The disease had destroyed Kristin’s vision and she was hoping the therapy, pioneered by jCyte, would help her. Kristin, being a bit of a pioneer herself, was the first person to test the therapy in the U.S.

Anyway, Kristin was doing a Zoom presentation and wanted to look her best so she asked a friend to come over and do her hair and makeup. The woman she asked, was Rosie Barrero, another patient in that RP clinical trial. Not so very long ago Rosie was legally blind. Now, here she was helping do her friend’s hair and makeup. And doing it beautifully too.

That’s when you know the treatment works. At least for Rosie.

There are many other stories to be heard – from patients and patient advocates, from researchers who develop therapies to the doctors who deliver them. – at our CIRM 2020 Grantee Meeting on next Monday September 14th Tuesday & September 15th.

It’s two full days of presentations and discussions on everything from heart disease and cancer, to COVID-19, Alzheimer’s, Parkinson’s and spina bifida. Here’s a link to the Eventbrite page where you can find out more about the event and also register to be part of it.

Like pretty much everything these days it’s a virtual event so you’ll be able to join in from the comfort of your kitchen, living room, even the backyard.

And it’s free!

You can join us for all two days or just one session on one day. The choice is yours. And feel free to tell your friends or anyone else you think might be interested.

We hope to see you there.