How quitting smoking helps your lungs regenerate; a discovery could lead to new ways to repair damaged lungs; and encouraging news in a stroke recovery trial

Photo courtesy Lindsay Fox

Smoking is one of the leading causes of preventable death not just in the US, but worldwide. According to the US Centers for Disease Control and Prevention tobacco causes an estimated seven million deaths around the world, every single year. And for every person who dies, another 30 live with a serious smoking-related illness. Clearly quitting is a good idea. Now a new study adds even more incentive to do just that.

Scientists at the Welcome Trust Sanger Institute and University College London in the UK, found that quitting smoking did more than just stop further damage to the lungs. They found that cells in the lining of the lungs that were able to avoid being damaged, were able to regrow and repopulate the lung, helping repair damaged areas.

In an article in Science Daily Dr Peter Campbell, a joint senior author of the study, said: “People who have smoked heavily for 30, 40 or more years often say to me that it’s too late to stop smoking — the damage is already done. What is so exciting about our study is that it shows that it’s never too late to quit — some of the people in our study had smoked more than 15,000 packs of cigarettes over their life, but within a few years of quitting many of the cells lining their airways showed no evidence of damage from tobacco.”

The study is published in the journal Nature.

Researchers at UCLA have also made a discovery that could help people with lung disease.

They examined the lungs of people with cancer and compared them to the lungs of healthy people. They were able to identify a group of molecules, called the Wnt/beta-catenin signaling pathway, that appear to influence the activity of stem cells that are key to maintaining healthy lungs. Too much activity can tilt the balance away from healthy lungs to ones with mutations that are more prone to developing tumors.

In a news release Dr. Brigitte Gomperts, the lead author of the study, says although this work has only been done in mice so far it has tremendous potential: “We think this could help us develop a new therapy that promotes airway health. This could not only inform the treatment of lung cancer, but help prevent its progression in the first place.”

The study is published in the journal Cell Reports.

CIRM has funded some of Dr. Gomperts earlier work in this area.

And there’s encouraging news for people trying to recover from a stroke. Results from ReNeuron’s Phase 2 clinical trial show the therapy appears to help people who have experienced some level of disability following a stroke.

ReNeuron says its CTX therapy – made from neural stem cells – was given to 23 people who had moderate to severe disability resulting from an ischemic stroke. The patients were, on average, seven months post stroke.

In the study, published in the Journal of Neurology, Neurosurgery & Psychiatry, researchers used the Modified Rankin Scale (mRS), a measure of disability and dependence to assess the impact of the therapy. The biggest improvements were seen in a group of 14 patients who had limited movement of one arm.

  • 38.5% experienced at least a one-point improvement on mRS six months after being treated.
  • 50% experienced a one-point improvement 12 months after being treated.

If that doesn’t seem like a big improvement, then consider this. Moving from an mRS 3 to 2 means that a person with a stroke regains their ability to live independently.

The therapy is now being tested in a larger patient group in the PISCES III clinical trial.

Rave reviews for new Killer-T Cell study

Anytime you read a news headline that claims a new discovery “may treat all cancer” it’s time to put your skeptic’s hat on. After all, there have been so many over-hyped “discoveries” over the years that later flopped, that it would be natural to question the headline writer. And yet, this time, maybe, this one has some substance behind it.

Andrew Sewell with research fellow Garry Dolton. (Photo Credit: Cardiff University)

Researchers at the University of Cardiff in Wales have discovered a new kind of immune cell, a so-called “killer T-cell”, that appears to be able to target and kill many human cancer cells, such as those found in breast, prostate and lung cancer. At least in the lab.

The immune system is our body’s defense against all sorts of threats, from colds and flu to cancer. But many cancers are able to trick the immune system and evade detection as they spread throughout the body. The researchers found one T-cell receptor (TCR) that appears to be able to identify cancer cells and target them, but leave healthy tissues alone.

In an interview with the BBC, Prof. Andrew Sewell, the lead researcher on the study said: “There’s a chance here to treat every patient. Previously nobody believed this could be possible. It raises the prospect of a ‘one-size-fits-all’ cancer treatment, a single type of T-cell that could be capable of destroying many different types of cancers across the population.”

The study, published in the journal Nature Immunology, suggests the TCR works by using a molecule called MR1 to identify cancerous cells. MR1 is found on every cell in our body but in cancerous cells it appears to give off a different signal, which enables the TCR to identify it as a threat.

When the researchers injected this TCR into mice that had cancer it was able to clear away many of the cells. The researchers admit there is still a long way to go before they know if this approach will work in people, but Sewell says they are encouraged by their early results.

“There are plenty of hurdles to overcome. However, if this testing is successful, then I would hope this new treatment could be in use in patients in a few years’ time.”

CIRM is funding a number of clinical trials that use a similar approach to targeting cancers, taking the patient’s own immune T-cells and, in the lab, “re-educating” to be able to recognize the cancerous cells. Those cells are then returned to the patient where it’s hoped they’ll identify and destroy the cancer. You can read about those here , here, here, here, and here.

Predicting the Impact of Stem Cell Cures on Healthcare Burden in California

A new independent report says developing stem cell treatments and cures for some of the most common and deadly diseases could produce multi-billion dollar benefits for California in reduced healthcare costs and improved quality and quantity of life.

The report, by researchers at the University of Southern California’s Leonard D. Schaeffer Center for Health Policy & Economics, looked at the value of hypothetical future interventions to reduce or cure cancer, diabetes, stroke and blindness.

Predicting the future is always complicated and uncertain and many groups are looking at the best models to determine the value and economic impact of cell and gene therapy as the first products are just entering the market. This study provides some insights into the potential financial benefits of developing effective stem cell treatments for some of the most intractable diseases affecting California today.

The impact could affect millions of people. In 2018 for Californians over the age of 50:

  • Nearly half were predicted to develop diabetes in their lifetime
  • More than one third will experience a stroke
  • Between 5 and 8 percent will develop either breast, colorectal, lung, or prostate cancer

The report says that a therapy that decreased the incidence of diabetes by 50 percent in Californians over the age of 51 would translate into a gain for the state of $322 billion in social value between now and 2050. Even just reducing diabetes 10% would lead to a gain of $60 billion in social value over the same period.

  • For stroke a 50 percent reduction would generate an estimated $229 billion in social value. A 10 percent reduction would generate $47 billion
  • For breast cancer a 50 percent reduction would generate $56 billion in social value; for colorectal cancer it would be $72 billion; for lung cancer $151 billion; and prostate cancer $53 billion. 

The impact of a cure for any one of those diseases would be enormous. For example, a 51-year-old woman cured of lung cancer could expect to gain a lifetime social value of almost half a million dollars ($467,275). That’s a measure of years of healthy life gained, of years spent enjoying time with family and friends and not wasting away or lying in a hospital bed.

The researchers say: “Though advances in scientific research defy easy predictions, investing in biomedical research is important if we want to reduce the burden of common and costly diseases for individuals, their families, and society. These findings show the value and impact breakthrough treatments could have for California.”

“Put in this context, the CIRM investment would be worthwhile if it increased our chances of success even modestly. Against the billions of dollars in disease burden facing California, the relatively small initial investment is already paying dividends as researchers work to bring new therapies to patients.”

The researchers determined the “social value” using a measure called a quality adjusted life-year (QALY). This is a way of estimating the cost effectiveness and consequences of treating or not treating a disease. For example, one QALY is equivalent to one year of perfect health for an individual. In this study the value of that year was estimated at $150,000. If someone is sick with, say, diabetes, their health would be estimated to be 0.5 QALY or $75,000. So, the better health a person enjoys and the longer they enjoy it the higher QALY score they accumulate. In the case of a disease affecting millions of people in that state or country that can obviously lead to very large QALY scores representing potentially billions of dollars.

Saying goodbye to a good friend and a stem cell pioneer: Karl Trede

FrankTrede_B_0110_20161204120959_2016_12_04_CIRM_AnnualReport_KarlTrede_SanJose_Portraits_SeesTheDay

Sometimes even courage and determination are not enough. Karl Trede had courage and determination in droves as he fought a 12 year battle against cancer. He recently lost that battle. But he remains an inspiration for all who knew him.

I got to know Karl for our 2016 Annual Report. Karl had been diagnosed with throat cancer in 2006. He underwent surgery to remove his vocal cords and the cancer seemed to be in remission. But then it returned, this time having spread to his lungs. His doctors said they had pretty much run out of options but would Karl consider trying something new, something no one else had tried before; stem cells.

Karl told me he didn’t hesitate.

“I said “sure”. I don’t believe I knew at the time that I was going to be the first one but I thought I’d give it a whirl. It was an experience for me. It was eye opening. I wasn’t real concerned about being the first, I figured I was going to have to go someday so I guess if I was the first person and something really went wrong then they’d definitely learn something. So, to me, that was kind of worth my time.”

Happily nothing went wrong and the team behind the therapy (Forty Seven Inc.) definitely learned something, they learned a lot about the correct dosage for patients; invaluable information in treating future patients.

Karl’s cancer was held at bay and he was able to do the one thing that brought him more pleasure than anything else; spend time with his family, his wife Vita, their four sons and their families. He doted on his grand kids and got to see them grow, and they got to know him.

Recently the cancer returned and this time there was no holding it at bay. To the end Karl remained cheerful and positive.

KARL poster

In our office is a huge poster of Karl with the words “Every Moment Counts” at the bottom. It’s a reminder to us why we come to work every day, why the people at Forty Seven Inc. and all the other researchers we support work so hard for years and years; to try and give people like Karl a few extra moments with his family.

At the top of the poster the word “Courage” is emblazoned across it. Karl has a huge smile on his face. Karl was certainly courageous, a stem cell pioneer willing to try something no one else ever had. He was also very modest.

Here is Karl speaking to our governing Board in December 2016

When I spoke to him in 2016, despite all he had gone through in his fight against cancer, he said he had no regrets:

“I consider myself very fortunate. I’m a lucky guy.”

Those of us who got to spend just a little time with Karl know that we were the lucky ones.

Our hearts go out to his family and friends for their loss.

 

 

CIRM invests in stem cell clinical trial targeting lung cancer and promising research into osteoporosis and incontinence

Lung cancer

Lung cancer: Photo courtesy Verywell

The five-year survival rate for people diagnosed with the most advanced stage of non-small cell lung cancer (NSCLC) is pretty grim, only between one and 10 percent. To address this devastating condition, the Board of the California Institute for Regenerative Medicine (CIRM) today voted to invest almost $12 million in a team from UCLA that is pioneering a combination therapy for NSCLC.

The team is using the patient’s own immune system where their dendritic cells – key cells in our immune system – are genetically modified to boost their ability to stimulate their native T cells – a type of white blood cell – to destroy cancer cells.  The investigators will combine this cell therapy with the FDA-approved therapy pembrolizumab (better known as Keytruda) a therapeutic that renders cancer cells more susceptible to clearance by the immune system.

“Lung cancer is a leading cause of cancer death for men and women, leading to 150,000 deaths each year and there is clearly a need for new and more effective treatments,” says Maria T. Millan, M.D., the President and CEO of CIRM. “We are pleased to support this program that is exploring a combination immunotherapy with gene modified cell and antibody for one of the most extreme forms of lung cancer.”

Translation Awards

The CIRM Board also approved investing $14.15 million in four projects under its Translation Research Program. The goal of these awards is to support promising stem cell research and help it move out of the laboratory and into clinical trials in people.

Researchers at Stanford were awarded almost $6 million to help develop a treatment for urinary incontinence (UI). Despite being one of the most common indications for surgery in women, one third of elderly women continue to suffer from debilitating urinary incontinence because they are not candidates for surgery or because surgery fails to address their condition.

The Stanford team is developing an approach using the patient’s own cells to create smooth muscle cells that can replace those lost in UI. If this approach is successful, it provides a proof of concept for replacement of smooth muscle cells that could potentially address other conditions in the urinary tract and in the digestive tract.

Max BioPharma Inc. was awarded almost $1.7 million to test a therapy that targets stem cells in the skeleton, creating new bone forming cells and blocking the destruction of bone cells caused by osteoporosis.

In its application the company stressed the benefit this could have for California’s diverse population stating: “Our program has the potential to have a significant positive impact on the lives of patients with osteoporosis, especially in California where its unique demographics make it particularly vulnerable. Latinos are 31% more likely to have osteoporosis than Caucasians, and California has the largest Latino population in the US, accounting for 39% of its population.”

Application Title Institution CIRM funding
TRAN1-10958 Autologous iPSC-derived smooth muscle cell therapy for treatment of urinary incontinence

 

 

Stanford University

 

$5,977,155

 

TRAN2-10990 Development of a noninvasive prenatal test for beta-hemoglobinopathies for earlier stem cell therapeutic interventions

 

 

Children’s Hospital Oakland Research Institute

 

$1,721,606

 

TRAN1-10937 Therapeutic development of an oxysterol with bone anabolic and anti-resorptive properties for intervention in osteoporosis  

MAX BioPharma Inc.

 

$1,689,855

 

TRAN1-10995 Morphological and functional integration of stem cell derived retina organoid sheets into degenerating retina models

 

 

UC Irvine

 

$4,769,039

 

Cells Behaving Badly: Rogue Stem Cells Set Stage for Lung Cancer, CIRM-Funded Study Finds

Occasionally, too much of a good thing can turn bad, an adage confirmed in a study published today by UCLA scientists.

Led by Dr. Brigitte Gomperts, a team of stem cell experts have honed in on how adult stem cells residing in the lung spring into action in order to repair damaged tissue. Normally, this process is vital for maintaining tissue health. But sometimes, things can go awry—thus setting the stage for cancer.

Scientists have hypothesized that some type of regulatory molecule pulled the strings—launching adult stem cells into action after injury or disease—but identifying that molecule had proven far more difficult.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

In this study, published online today in the journal Stem Cell, Dr. Gomperts and her team believe they have found this molecular puppet master: a class of molecules called reactive oxygen species, or ROS.

Recently, scientists observed low levels of ROS to play a role in maintaining a variety of cellular functions. They had also noticed that while low-to-moderate ROS levels were essential, any spike in ROS appeared to have a toxic effect on the cell.

In this study, which was supported by a CIRM New Faculty Award, the UCLA team found that a ‘dynamic flux’ in ROS levels from low to moderate helped drive adult stem cells to grow and divide at regular rates and repair damaged tissue. But when ROS levels got too high, the stem cells started dividing out of control, leading to what Gomperts called “pre-cancerous lesions.”

As she explained in today’s news release:

“Low ROS is what keeps stem cells in a ready state so that your body is poised and ready to respond to injury and repair. Loss of this ROS regulation leads to pre-cancerous lesions.”

Importantly, the team noted that many environmental factors are linked to an increase in ROS levels—such as exposure to cigarette smoke, smog or pathogens. Lung cancer remains the deadliest form of cancer in the United States. Therefore, finding a way to identify the cancer in this early, pre-cancerous stage, is crucial for reducing the risk of death.

As Gomperts put it:

“Now, with this precancerous model in place, we can begin looking for what we call ‘driver mutations,’ or those specific changes that take the pre-cancerous lesion to full-blown cancer.”

Gomperts is optimistic that this ‘personalized’ approach to drug discovery will lead to more effective therapies:

“There are likely multiple ways for a patient to get a pre-cancerous lesion so the process could be different amongst different groups of people. Imagine a personalized way to identify what pathways have gone wrong in a patient, so that we could target a therapy to that individual.”

Cells Behaving Badly: Rogue Stem Cells Set Stage for Lung Cancer, CIRM-Funded Study Finds

Occasionally, too much of a good thing can turn bad, an adage confirmed in a study published today by UCLA scientists.

Led by Dr. Brigitte Gomperts, a team of stem cell experts have honed in on how adult stem cells residing in the lung spring into action in order to repair damaged tissue. Normally, this process is vital for maintaining tissue health. But sometimes, things can go awry—thus setting the stage for cancer.

Scientists have hypothesized that some type of regulatory molecule pulled the strings—launching adult stem cells into action after injury or disease—but identifying that molecule had proven far more difficult.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

In this study, published online today in the journal Stem Cell, Dr. Gomperts and her team believe they have found this molecular puppet master: a class of molecules called reactive oxygen species, or ROS.

Recently, scientists observed low levels of ROS to play a role in maintaining a variety of cellular functions. They had also noticed that while low-to-moderate ROS levels were essential, any spike in ROS appeared to have a toxic effect on the cell.

In this study, which was supported by a CIRM New Faculty Award, the UCLA team found that a ‘dynamic flux’ in ROS levels from low to moderate helped drive adult stem cells to grow and divide at regular rates and repair damaged tissue. But when ROS levels got too high, the stem cells started dividing out of control, leading to what Gomperts called “pre-cancerous lesions.”

As she explained in today’s news release:

“Low ROS is what keeps stem cells in a ready state so that your body is poised and ready to respond to injury and repair. Loss of this ROS regulation leads to pre-cancerous lesions.”

Importantly, the team noted that many environmental factors are linked to an increase in ROS levels—such as exposure to cigarette smoke, smog or pathogens. Lung cancer remains the deadliest form of cancer in the United States. Therefore, finding a way to identify the cancer in this early, pre-cancerous stage, is crucial for reducing the risk of death.

As Gomperts put it:

“Now, with this precancerous model in place, we can begin looking for what we call ‘driver mutations,’ or those specific changes that take the pre-cancerous lesion to full-blown cancer.”

Gomperts is optimistic that this ‘personalized’ approach to drug discovery will lead to more effective therapies:

“There are likely multiple ways for a patient to get a pre-cancerous lesion so the process could be different amongst different groups of people. Imagine a personalized way to identify what pathways have gone wrong in a patient, so that we could target a therapy to that individual.”