About one third of stroke survivors experience vision loss. It can be a devastating side effect as most patients will not fully recover their vision and there are currently no reliable treatments available. But thanks to a collaborative effort by two teams of researchers from Purdue University and Jinan University in China, there may be a way to use gene therapy to recover lost vision after a stroke.
A stroke happens when part of the brain is starved of oxygen which can result in death of brain cells or neurons. Oftentimes this is caused by a blockage in an artery in the brain. Given the location of these vital arteries, most strokes lead to loss of motor function and in some cases, permanent vision loss.
The brain is an incredible machine and capable of remapping its neural pathways enough to restore some visual function, but this isn’t always the case. The neurons that are destroyed in the process of experiencing a stroke do not regenerate and lose their ability to communicate/transmit information between different areas of the brain, and between the brain and the rest of the nervous system.
Two research teams, one led by Alexander Chubykin at Purdue University’s and the other led by Gong Chen at Jinan University, have taken a different approach to neural regeneration by reprogramming local glial cells into neurons, therefore restoring connections between the old neurons and the newly reprogrammed neurons.
In a news release, Dr. Chubykin says the results in the lab look promising. “We can watch the mice get their vision back. We don’t have to implant new cells, so there’s no immunogenic rejection. This process is easier to do than stem cell therapy, and there’s less damage.”
The collaborative research, published in the journal Frontiers in Cell and Developmental Biology, is promising not only in aiding with vision restoration after a stroke but could also lead to similar treatment for reestablishing motor function. Visual function is easier than motor skills to measure accurately and the scientists are looking into the effectiveness of this procedure in live mice using advanced optical imaging tools. If the study continues to provide positive results, it might not be long before human trials are started.
Heart disease and stroke are two of the leading causes of death and disability and for people who have experienced either their treatment options are very limited. Current therapies focus on dealing with the immediate impact of the attack, but there is nothing to deal with the longer-term impact. The CIRM Board hopes to change that by funding promising work for both conditions.
Dr. Gary Steinberg and his team at Stanford were awarded almost $12 million to conduct a clinical trial to test a therapy for motor disabilities caused by chronic ischemic stroke. While “clot busting” therapies can treat strokes in their acute phase, immediately after they occur, these treatments can only be given within a few hours of the initial injury. There are no approved therapies to treat chronic stroke, the disabilities that remain in the months and years after the initial brain attack.
Dr. Steinberg will use embryonic stem cells that have been turned into neural stem cells (NSCs), a kind of stem cell that can form different cell types found in the brain. In a surgical procedure, the team will inject the NSCs directly into the brains of chronic stroke patients. While the ultimate goal of the therapy is to restore loss of movement in patients, this is just the first step in clinical trials for the therapy. This first-in-human trial will evaluate the therapy for safety and feasibility and look for signs that it is helping patients.
Another Stanford researcher, Dr. Crystal Mackall, was also awarded almost $12 million to conduct a clinical trial to test a treatment for children and young adults with glioma, a devastating, aggressive brain tumor that occurs primarily in children and young adults and originates in the brain. Such tumors are uniformly fatal and are the leading cause of childhood brain tumor-related death. Radiation therapy is a current treatment option, but it only extends survival by a few months.
Dr. Crystal Mackall and her team will modify a patient’s own T cells, an immune system cell that can destroy foreign or abnormal cells. The T cells will be modified with a protein called chimeric antigen receptor (CAR), which will give the newly created CAR-T cells the ability to identify and destroy the brain tumor cells. The CAR-T cells will be re-introduced back into patients and the therapy will be evaluated for safety and efficacy.
Stanford made it three in a row with the award of almost $7 million to Dr. Joe Wu to test a therapy for left-sided heart failure resulting from a heart attack. The major issue with this disease is that after a large number of heart muscle cells are killed or damaged by a heart attack, the adult heart has little ability to repair or replace these cells. Thus, rather than being able to replenish its supply of muscle cells, the heart forms a scar that can ultimately cause it to fail.
Dr. Wu will use human embryonic stem cells (hESCs) to generate cardiomyocytes (CM), a type of cell that makes up the heart muscle. The newly created hESC-CMs will then be administered to patients at the site of the heart muscle damage in a first-in-human trial. This initial trial will evaluate the safety and feasibility of the therapy, and the effect upon heart function will also be examined. The ultimate aim of this approach is to improve heart function for patients suffering from heart failure.
“We are pleased to add these clinical trials to CIRM’s portfolio,” says Maria T. Millan, M.D., President and CEO of CIRM. “Because of the reauthorization of CIRM under Proposition 14, we have now directly funded 75 clinical trials. The three grants approved bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures.”
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.
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 email@example.com.
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).
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.
Stroke is the third leading cause of death and serious long-term disability and affects nearly 800,000 Americans a year, with someone in the U.S. suffering a stroke every 40 seconds. Roughly 87% of all strokes are ischemic strokes, meaning that a clot blocks blood flow to the brain. Unfortunately 90% of those who suffer an ischemic stroke also end up suffering from weakness or paralysis to one side of the body.
A study conducted by Muhammad Haque, Ph.D. and Sean Savitz, M.D. at The University of Texas Health Science Center at Houston (UTHealth) found that treating patients with stem cells from their own bone marrow could lead to a reduction in brain injury after a stroke caused by a blood clot.
For this study, there were 37 patients from ages 18 to 80. While all received the standard stroke treatment and rehabilitation follow-up, 17 patients whose strokes were the most severe received a bone marrow stem cell therapy. To measure any improvement, the UTHealth team used 3D brain imaging of the patients obtained from MRI scans. They used these images to compare changes in white matter of those treated with their own bone marrow stem cells to those who were not treated.
White matter is a specific type of tissue in the brain that is critical for motor function because it is responsible for carrying movement-related information to the spinal cord.
Three months after the stroke, the MRI scans of each patient showed the expected decrease after a stroke. However, scans taken 12 months after the stroke occurred showed an improvement on average in the 17 patients who received bone marrow cell therapy.
In a press release from UTHealth, Dr. Haque elaborates on what these results could mean for developing treamtents for stroke patients.
“We envision that future clinical trials might be directed toward identifying white matter protection or repair as an important mechanistic target of efficacy studies and potency assays for bone marrow cell therapies.”
The full results to this study were published in STEM CELLS Translational Medicine.
Stroke is the third leading cause of death and disability in the US. Every 45 seconds someone in the US has a stroke. Every year around 275,000 people die from a stroke many more survive but are often impaired by the brain attack. The impact is not just physical, but psychological and emotional. It takes an enormous toll on individuals and their families. So, it’s not surprising that there is a lot of research underway to try and find treatments to help people, including using stem cells.
That’s why CIRM is hosting a special Facebook Live ‘Ask the Stem Cell Team About Stroke event on Wednesday, March 25th at noon PDT. Just head over to our Facebook Page on the 25th at noon to hear from two great guests.
We will be joined by Dr. Tom Carmichael, a Professor of Neurology and the Co-Director of the UCLA Broad Stem Cell Center. He has a number of CIRM grants focused on helping repair the damage caused by strokes.
CIRM Senior Science Officer, Dr. Lila Collins, will also join us to talk about other stem cell research targeting stroke, its promise and some of the problems that still need to be overcome.
You will have a chance to ask questions of both our experts, either live on the day or by sending us questions in advance at firstname.lastname@example.org.
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.”
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.”
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.
This year the most widely read blog was actually one we wrote back in 2018. It’s the transcript of a Facebook Live: “Ask the Stem Cell Team” event about strokes and stroke recovery. Because stroke is the third leading cause of death and disability in the US it’s probably no surprise this blog has lasting power. So many people are hoping that stem cells will help them recover from a stroke.
But of the blogs that we wrote and posted this year there’s a really interesting mix of topics.
The most read 2019 blog was about a potential breakthrough in the search for a treatment for type 1 diabetes (T1D). Two researchers at UC San Francisco, Dr. Matthias Hebrok and Dr. Gopika Nair developed a new method of replacing the insulin-producing cells in the pancreas that are destroyed by type 1 diabetes.
Dr. Hebrok described it as a big advance saying: “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”
It’s not too surprising a blog about type 1 diabetes was at the top. This condition affects around 1.25 million Americans, a huge audience for any potential breakthrough. However, the blog that was the second most read is the exact opposite. It is about a rare disease called cystinosis. How rare? Well, there are only around 500 children and young adults in the US, and just 2,000 worldwide diagnosed with this condition.
It might be rare but its impact is devastating. A genetic mutation means children with this condition lack the ability to clear an amino acid – cysteine – from their body. The buildup of cysteine leads to damage to the kidneys, eyes, liver, muscles, pancreas and brain.
UC San Diego researcher Dr. Stephanie Cherqui and her team are taking the patient’s own blood stem cells and, in the lab, genetically re-engineering them to correct the mutation, then returning the cells to the patient. It’s hoped this will create a new, healthy blood system free of the disease.
Dr. Cherqui says if it works, this could help not just people with cystinosis but a wide array of other disorders: “We were thrilled that the stem cells and gene therapy worked so well to prevent tissue degeneration in the mouse model of cystinosis. This discovery opened new perspectives in regenerative medicine and in the application to other genetic disorders. Our findings may deliver a completely new paradigm for the treatment of a wide assortment of diseases including kidney and other genetic disorders.”
The third most read blog was about another rare disease, but one that has been getting a lot of media attention this past year. Sickle cell disease affects around 100,000 Americans, mostly African Americans. In November the Food and Drug Administration (FDA) approved Oxbryta, a new therapy that reduces the likelihood of blood cells becoming sickle shaped and clumping together – causing blockages in blood vessels.
But our blog focused on a stem cell approach that aims to cure the disease altogether. In many ways the researchers in this story are using a very similar approach to the one Dr. Cherqui is using for cystinosis. Genetically correcting the mutation that causes the problem, creating a new, healthy blood system free of the sickle shaped blood cells.
Two other blogs deserve honorable mentions here as well. The first is the story of James O’Brien who lost the sight in his right eye when he was 18 years old and now, 25 years later, has had it restored thanks to stem cells.
The fifth most popular blog of the year was another one about type 1 diabetes. This piece focused on the news that the CIRM Board had awarded more than $11 million to Dr. Peter Stock at UC San Francisco for a clinical trial for T1D. His approach is transplanting donor pancreatic islets and parathyroid glands into patients, hoping this will restore the person’s ability to create their own insulin and control the disease.
2019 was certainly a busy year for CIRM. We are hoping that 2020 will prove equally busy and give us many new advances to write about. You will find them all here, on The Stem Cellar.
On December 12th we hosted our latest ‘Facebook Live: Ask the Stem Cell Team’ event. This time around we really did mean team. We had a host of our Science Officers answering questions from friends and supporters of CIRM. We got a lot of questions and didn’t have enough time to address them all. So here’s answers to all the questions.
What are the obstacles to using partial cellular reprogramming to return people’s entire bodies to a youthful state.Paul Hartman. San Leandro, California
Dr. Kelly Shepard: Certainly, scientists have observed that various manipulations of cells, including reprogramming, partial reprogramming, de-differentiation and trans-differentiation, can restore or change properties of cells, and in some cases, these changes can reflect a more “youthful” state, such as having longer telomeres, better proliferative capacity, etc. However, some of these same rejuvenating properties, outside of their normal context, could be harmful or deadly, for example if a cell began to grow and divide when or where it shouldn’t, similar to cancer. For this reason, I believe the biggest obstacles to making this approach a reality are twofold: 1) our current, limited understanding of the nature of partially reprogrammed cells; and 2) our inability to control the fate of those cells that have been partially reprogrammed, especially if they are inside a living organism. Despite the challenges, I think there will be step wise advances where these types of approaches will be applied, starting with specific tissues. For example, CIRM has recently funded an approach that uses reprogramming to make “rejuvenated” versions of T cells for fighting lung cancer. There is also a lot of interest in using such approaches to restore the reparative capacity of aged muscle. Perhaps some successes in these more limited areas will be the basis for expanding to a broader use.
What’s going on with Stanford’s stem cell trials for stroke? I remember the first trial went really well In 2016 have not heard anything about since? Elvis Arnold
Dr. Lila Collins: Hi Elvis, this is an evolving story. I believe you are referring to SanBio’s phase 1/2a stroke trial, for which Stanford was a site. This trial looked at the safety and feasibility of SanBio’s donor or allogeneic stem cell product in chronic stroke patients who still had motor deficits from their strokes, even after completing physical therapy when natural recovery has stabilized. As you note, some of the treated subjects had promising motor recoveries.
SanBio has since completed a larger, randomized phase 2b trial in stroke, and they have released the high-level results in a press release. While the trial did not meet its primary endpoint of improving motor deficits in chronic stroke, SanBio conducted a very similar randomized trial in patients with stable motor deficits from chronic traumatic brain injury (TBI). In this trial, SanBio saw positive results on motor recovery with their product. In fact, this product is planned to move towards a conditional approval in Japan and has achieved expedited regulatory status in the US, termed RMAT, in TBI which means it could be available more quickly to patients if all goes well. SanBio plans to continue to investigate their product in stroke, so I would stay tuned as the work unfolds.
Also, since you mentioned Stanford, I should note that Dr Gary Steinberg, who was a clinical investigator in the SanBio trial you mentioned, will soon be conducting a trial with a different product that he is developing, neural progenitor cells, in chronic stroke. The therapy looks promising in preclinical models and we are hopeful it will perform well for patients in the clinic.
I am a stroke survivor will stem cell treatment able to restore my motor skills?Ruperto
Dr. Lila Collins:
Hi Ruperto. Restoring motor loss after stroke is a very active area of research. I’ll touch upon a few ongoing stem cell trials. I’d just like to please advise that you watch my colleague’s comments on stem cell clinics (these can be found towards the end of the blog) to be sure that any clinical research in which you participate is as safe as possible and regulated by FDA.
Back to stroke, I mentioned SanBio’s ongoing work to address motor skill loss in chronic stroke earlier. UK based Reneuron is also conducting a phase 2 trial, using a neural progenitor cell as a candidate therapy to help recover persistent motor disability after stroke (chronic). Dr Gary Steinberg at Stanford is also planning to conduct a clinical trial of a human embryonic stem cell-derived neuronal progenitor cell in stroke.
There is also promising work being sponsored by Athersys in acute stroke. Athersys published results from their randomized, double blinded placebo controlled Ph2 trial of their Multistem product in patients who had suffered a stroke within 24-48 hours. After intravenous delivery, the cells improved a composite measure of stroke recovery, including motor recovery. Rather than acting directly on the brain, Multistem seems to work by traveling to the spleen and reducing the inflammatory response to a stroke that can make the injury worse.
Athersys is currently recruiting a phase 3 trial of its Multistem product in acute stroke (within 1.5 days of the stroke). The trial has an accelerated FDA designation, called RMAT and a special protocol assessment. This means that if the trial is conducted as planned and it reaches the results agreed to with the FDA, the therapy could be cleared for marketing. Results from this trial should be available in about two years.
Questions from several hemorrhagic stroke survivors who say most clinical trials are for people with ischemic strokes. Could stem cells help hemorrhagic stroke patients as well?
Dr. Lila Collins:
Regarding hemorrhagic stroke, you are correct the bulk of cell therapies for stroke target ischemic stroke, perhaps because this accounts for the vast bulk of strokes, about 85%.
That said, hemorrhagic strokes are not rare and tend to be more deadly. These strokes are caused by bleeding into or around the brain which damages neurons. They can even increase pressure in the skull causing further damage. Because of this the immediate steps treating these strokes are aimed at addressing the initial bleeding insult and the blood in the brain.
While most therapies in development target ischemic stroke, successful therapies developed to repair neuronal damage or even some day replace lost neurons, could be beneficial after hemorrhagic stroke as well.
I had an Ischemic stroke in 2014, and my vision was also affected. Can stem cells possibly help with my vision issues. James Russell
Dr. Lila Collins:
Hi James. Vision loss from stroke is complex and the type of loss depends upon where the stroke occurred (in the actual eye, the optic nerve or to the other parts of the brain controlling they eye or interpreting vision). The results could be:
Visual loss from damage to the retina
You could have a normal eye with damage to the area of the brain that controls the eye’s movement
You could have damage to the part of the brain that interprets vision.
You can see that to address these various issues, we’d need different cell replacement approaches to repair the retina or the parts of the brain that were damaged.
Replacing lost neurons is an active effort that at the moment is still in the research stages. As you can imagine, this is complex because the neurons have to make just the right connections to be useful.
Is there any stem cell therapy for optical nerve damage? Deanna Rice
Dr. Ingrid Caras: There is currently no proven stem cell therapy to treat optical nerve damage, even though there are shady stem cell clinics offering treatments. However, there are some encouraging early gene therapy studies in mice using a virus called AAV to deliver growth factors that trigger regeneration of the damaged nerve. These studies suggest that it may be possible to restore at least some visual function in people blinded by optic nerve damage from glaucoma
I read an article about ReNeuron’s retinitis pigmentosa clinical trial update. In the article, it states: “The company’s treatment is a subretinal injection of human retinal progenitors — cells which have almost fully developed into photoreceptors, the light-sensing retinal cells that make vision possible.” My question is: If they can inject hRPC, why not fully developed photoreceptors?Leonard
Dr. Kelly Shepard: There is evidence from other studies, including from other tissue types such as blood, pancreas, heart and liver, that fully developed (mature) cell types tend not to engraft as well upon transplantation, that is the cells do not establish themselves and survive long term in their new environment. In contrast, it has been observed that cells in a slightly less “mature” state, such as those in the progenitor stage, are much more likely to establish themselves in a tissue, and then differentiate into more mature cell types over time. This question gets at the crux of a key issue for many new therapies, i.e. what is the best cell type to use, and the best timing to use it.
My question for the “Ask the Stem Cell Team” event is: When will jCyte publish their Phase IIb clinical trial results. Chris Allen
Dr. Ingrid Caras: The results will be available sometime in 2020.
I understand the hRPC cells are primarily neurotropic (rescue/halt cell death); however, the literature also says hRPC can become new photoreceptors. My questions are:Approximately what percentage develop into functioning photoreceptors? And what percentage of the injected hRPC are currently surviving?Leonard Furber, an RP Patient
Dr. Kelly Shepard: While we can address these questions in the lab and in animal models, until there is a clinical trial, it is not possible to truly recreate the environment and stresses that the cells will undergo once they are transplanted into a human, into the site where they are expected to survive and function. Thus, the true answer to this question may not be known until after clinical trials are performed and the results can be evaluated. Even then, it is not always possible to monitor the fate of cells after transplantation without removing tissues to analyze (which may not be feasible), or without being able to transplant labeled cells that can be readily traced.
Dr. Ingrid Caras – Although the cells have been shown to be capable of developing into photoreceptors, we don’t know if this actually happens when the cells are injected into a patient’s eye. The data so far suggest that the cells work predominantly by secreting growth factors that rescue damaged retinal cells or even reverse the damage. So one possible outcome is that the cells slow or prevent further deterioration of vision. But an additional possibility is that damaged retinal cells that are still alive but are not functioning properly may become healthy and functional again which could result in an improvement in vision.
What advances have been made using stem cells for the treatment of Type 2 Diabetes?Mary Rizzo
Dr. Ross Okamura: Type 2 Diabetes (T2D) is a disease where the body is unable to maintain normal glucose levels due to either resistance to insulin-regulated control of blood sugar or insufficient insulin production from pancreatic beta cells. The onset of disease has been associated with lifestyle influenced factors including body mass, stress, sleep apnea and physical activity, but it also appears to have a genetic component based upon its higher prevalence in certain populations.
Type 1 Diabetes (T1D) differs from T2D in that in T1D patients the pancreatic beta cells have been destroyed by the body’s immune system and the requirement for insulin therapy is absolute upon disease onset rather than gradually developing over time as in many T2D cases. Currently the only curative approach to alleviate the heavy burden of disease management in T1D has been donor pancreas or islet transplantation. However, the supply of donor tissue is small relative to the number of diabetic patients. Donor islet and pancreas transplants also require immune suppressive drugs to prevent allogenic immune rejection and the use of these drugs carry additional health concerns. However, for some patients with T1D, especially those who may develop potentially fatal hypoglycemia, immune suppression is worth the risk.
To address the issue of supply, there has been significant activity in stem cell research to produce insulin secreting beta cells from pluripotent stem cells and recent clinical data from Viacyte’s CIRM funded trial indicates that implanted allogeneic human stem cell derived cells in T1D patients can produce circulating c-peptide, a biomarker for insulin. While the trial is not designed specifically to cure insulin-dependent T2D patients, the ability to produce and successfully engraft stem cell-derived beta cells would be able to help all insulin-dependent diabetic patients.
It’s also worth noting that there is a sound scientific reason to clinically test a patient-derived pluripotent stem cell-based insulin-producing cells in insulin-dependent T2D diabetic patients; the cells in this case could be evaluated for their ability to cure diabetes in the absence of needing to prevent both allogeneic and autoimmune responses.
SPINAL CORD INJURY
Is there any news on clinical trials for spinal cord injury? Le Ly
Kevin McCormack: The clinical trial CIRM was funding, with Asterias (now part of a bigger company called Lineage Cell Therapeutics, is now completed and the results were quite encouraging. In a news release from November of 2019 Brian Culley, CEO of Lineage Cell Therapeutics, described the results this way.
“We remain extremely excited about the potential for OPC1 (the name of the therapy used) to provide enhanced motor recovery to patients with spinal cord injuries. We are not aware of any other investigative therapy for SCI (spinal cord injury) which has reported as encouraging clinical outcomes as OPC1, particularly with continued improvement beyond 1 year. Overall gains in motor function for the population assessed to date have continued, with Year 2 assessments measuring the same or higher than at Year 1. For example, 5 out of 6 Cohort 2 patients have recovered two or more motor levels on at least one side as of their Year 2 visit whereas 4 of 6 patients in this group had recovered two motor levels as of their Year 1 visit. To put these improvements into perspective, a one motor level gain means the ability to move one’s arm, which contributes to the ability to feed and clothe oneself or lift and transfer oneself from a wheelchair. These are tremendously meaningful improvements to quality of life and independence. Just as importantly, the overall safety of OPC1 has remained excellent and has been maintained 2 years following administration, as measured by MRI’s in patients who have had their Year 2 follow-up visits to date. We look forward to providing further updates on clinical data from SCiStar as patients continue to come in for their scheduled follow up visits.”
Lineage Cell Therapeutics plans to meet with the FDA in 2020 to discuss possible next steps for this therapy.
In the meantime the only other clinical trial I know that is still recruiting is one run by a company called Neuralstem. Here is a link to information about that trial on the www.clinicaltrials.gov website.
Now that the Brainstorm ALS trial is finished looking for new patients do you have any idea how it’s going and when can we expect to see results? Angela Harrison Johnson
Dr. Ingrid Caras: The treated patients have to be followed for a period of time to assess how the therapy is working and then the data will need to be analyzed. So we will not expect to see the results probably for another year or two.
Are there treatments for autism or fragile x using stem cells? Magda Sedarous
Dr. Kelly Shepard: Autism and disorders on the autism spectrum represent a collection of many different disorders that share some common features, yet have different causes and manifestations, much of which we still do not understand. Knowing the origin of a disorder and how it affects cells and systems is the first step to developing new therapies. CIRM held a workshop on Autism in 2009 to brainstorm potential ways that stem cell research could have an impact. A major recommendation was to exploit stem cells and new technological advances to create cells and tissues, such as neurons, in the lab from autistic individuals that could then be studied in great detail. CIRM followed this recommendation and funded several early-stage awards to investigate the basis of autism, including Rett Syndrome, Fragile X, Timothy Syndrome, and other spectrum disorders. While these newer investigations have not yet led to therapies that can be tested in humans, this remains an active area of investigation. Outside of CIRM funding, we are aware of more mature studies exploring the effects of umbilical cord blood or other specific stem cell types in treating autism, such as an ongoing clinical trial conducted at Duke University.
What is happening with Parkinson’s research? Hanifa Gaphoor
Dr. Kent Fitzgerald: Parkinson’s disease certainly has a significant amount of ongoing work in the regenerative medicine and stem cell research.
The nature of cell loss in the brain, specifically the dopaminergic cells responsible for regulating the movement, has long been considered a good candidate for cell replacement therapy.
This is largely due to the hypothesis that restoring function to these cells would reverse Parkinson’s symptoms. This makes a lot of sense as front line therapy for the disease for many years has been dopamine replacement through L-dopa pills etc. Unfortunately, over time replacing dopamine through a pill loses its benefit, whereas replacing or fixing the cells themselves should be a more permanent fix.
Because a specific population of cells in one part of the brain are lost in the disease, multiple labs and clinicians have sought to replace or augment these cells by transplantation of “new” functional cells able to restore function to the area an theoretically restore voluntary motor control to patients with Parkinson’s disease.
Early clinical research showed some promise, however also yielded mixed results, using fetal tissue transplanted into the brains of Parkinson’s patients. As it turns out, the cell types required to restore movement and avoid side effects are somewhat nuanced. The field has moved away from fetal tissue and is currently pursuing the use of multiple stem cell types that are driven to what is believed to be the correct subtype of cell to repopulate the lost cells in the patient.
One project CIRM sponsored in this area with Jeanne Loring sought to develop a cell replacement therapy using stem cells from the patients themselves that have been reprogrammed into the kinds of cell damaged by Parkinson’s. This type of approach may ultimately avoid issues with the cells avoiding rejection by the immune system as can be seen with other types of transplants (i.e. liver, kidney, heart etc).
Still, others are using cutting edge gene therapy technology, like the clinical phase project CIRM is sponsoring with Krystof Bankiewicz to investigate the delivery of a gene (GDNF) to the brain that may help to restore the activity of neurons in the Parkinson’s brain that are no longer working as they should.
The bulk of the work in the field of PD at the present remains centered on replacing or restoring the dopamine producing population of cells in the brain that are affected in disease.
Any plans for Huntington’s?Nikhat Kuchiki
Dr. Lisa Kadyk: The good news is that there are now several new therapeutic approaches to Huntington’s Disease that are at various stages of preclinical and clinical development, including some that are CIRM funded. One CIRM-funded program led by Dr. Leslie Thompson at UC Irvine is developing a cell-based therapeutic that consists of neural stem cells that have been manufactured from embryonic stem cells. When these cells are injected into the brain of a mouse that has a Huntington’s Disease mutation, the cells engraft and begin to differentiate into new neurons. Improvements are seen in the behavioral and electrophysiological deficits in these mutant mice, suggesting that similar improvements might be seen in people with the disease. Currently, CIRM is funding Dr. Thompson and her team to carry out rigorous safety studies in animals using these cells, in preparation for submitting an application to the FDA to test the therapy in human patients in a clinical trial.
There are other, non-cell-based therapies also being tested in clinical trials now, using anti-sense oligonucleotides (Ionis, Takeda) to lower the expression of the Huntington protein. Another HTT-lowering approach is similar – but uses miRNAs to lower HTT levels (UniQure,Voyager)
TRAUMATIC BRAIN INJURY (TBI)
My 2.5 year old son recently suffered a hypoxic brain injury resulting in motor and speech disabilities. There are several clinical trials underway for TBI in adults. My questions are:
Will the results be scalable to pediatric use and how long do you think it would take before it is available to children?
I’m wondering why the current trials have chosen to go the route of intracranial injections as opposed to something slightly less invasive like an intrathecal injection?
Is there a time window period in which stem cells should be administered by, after which the administration is deemed not effective?
Dr. Kelly Shepard: TBI and other injuries of the nervous system are characterized by a lot of inflammation at the time of injury, which is thought to interfere with the healing process- and thus some approaches are intended to be delivered after that inflammation subsides. However, we are aware of approaches that intend to deliver a therapy to a chronic injury, or one that has occurred previously. Thus, the answer to this question may depend on how the intended therapy is supposed to work. For example, is the idea to grow new neurons, or is it to promote the survival of neurons of other cells that were spared by the injury? Is the therapy intended to address a specific symptom, such as seizures? Is the therapy intended to “fill a gap” left behind after inflammation subsides, which might not restore all function but might ameliorate certain symptoms.? There is still a lot we don’t understand about the brain and the highly sophisticated network of connections that cannot be reversed by only replacing neurons, or only reducing inflammation, etc. However, if trials are well designed, they should yield useful information even if the therapy is not as effective as hoped, and this information will pave the way to newer approaches and our technology and understanding evolves.
We have had a doctor recommending administering just the growth factors derived from MSC stem cells. Does the science work that way? Is it possible to isolate the growth factors and boost the endogenous growth factors by injecting allogenic growth factors?
Dr. Stephen Lin: Several groups have published studies on the therapeutic effects in non-human animal models of using nutrient media from MSC cultures that contain secreted factors, or extracellular vesicles from cells called exosomes that carry protein or nucleic acid factors. Scientifically it is possible to isolate the factors that are responsible for the therapeutic effect, although to date no specific factor or combination of factors have been identified to mimic the effects of the undefined mixtures in the media and exosomes. At present no regulatory approved clinical therapy has been developed using this approach.
PREDATORY STEM CELL CLINICS
What practical measures are being taken to address unethical practitioners whose bad surgeries are giving stem cell advances a bad reputation and are making forward research difficult?Kathy Jean Schultz
Dr. Geoff Lomax: Terrific question! I have been doing quite a bit research into the history of this issue of unethical practitioners and I found an 1842 reference to “quack medicines.” Clearly this is nothing new. In that day, the author appealed to make society “acquainted with the facts.”
In California, we have taken steps to (1) acquaint patients with the facts about stem cell treatments and (2) advance FDA authorized treatments for unmet medical needs.
First, CIRM work with Senator Hernandez in 2017 to write a law the requires provides to disclose to patient that a stem cell therapy has not been approved by the Food and Drug administration.
We continue to work with the State Legislature and Medical Board of California to build on policies that require accurate disclosure of the facts to patients.
Second, our clinical trial network the — Alpha Stem Cell Clinics – have supported over 100 FDA-authorized clinical trials to advance responsible clinical research for unmet medical needs.
I’m curious if adipose stem cell being used at clinics at various places in the country is helpful or beneficial?Cheri Hicks
Adipose tissue has been widely used particularly in plastic and reconstructive surgery. Many practitioners suggest adipose cells are beneficial in this context. With regard to regenerative medicine and / or the ability to treat disease and injury, I am not aware of any large randomized clinical trials that demonstrate the safety and efficacy of adipose-derived stem cells used in accordance with FDA guidelines.
I went to a “Luncheon about Stem Cell Injections”. It sounded promising. I went thru with it and got the injections because I was desperate from my knee pain. The price of stem cell injections was $3500 per knee injection. All went well. I have had no complications, but haven’t noticed any real major improvement, and here I am a year later. My questions are:
1) I wonder on where the typical injection cells are coming from?
2) I wonder what is the actual cost of the cells?
3) What kind of results are people getting from all these “pop up” clinics or established clinics that are adding this to there list of offerings?
Dr. Geoff Lomax: You raise a number of questions and point here; they are all very good and it’s is hard to give a comprehensive response to each one, but here is my reaction:
There are many practitioners in the field of orthopedics who sincerely believe in the potential of cell-based treatments to treat injury / pain
Most of the evidence presented is case reports that individuals have benefited
The challenge we face is not know the exact type of injury and cell treatments used.
Well controlled clinical trials would really help us understand for what cells (or cell products) and for what injury would be helpful
Prices of $3000 to $5000 are not uncommon, and like other forms of private medicine there is often a considerable mark-up in relation to cost of goods.
You are correct that there have not been reports of serious injury for knee injections
However the effectiveness is not clear while simultaneously millions of people have been aided by knee replacements.
Do stem cells have benefits for patients going through chemotherapy and radiation therapy?Ruperto
Dr. Kelly Shepard: The idea that a stem cell therapy could help address effects of chemotherapy or radiation is being and has been pursued by several investigators over the years, including some with CIRM support. Towards the earlier stages, people are looking at the ability of different stem cell-derived neural cell preparations to replace or restore function of certain brain cells that are damaged by the effects of chemotherapy or radiation. In a completely different type of approach, a group at City of Hope is exploring whether a bone marrow transplant with specially modified stem cells can provide a protective effect against the chemotherapy that is used to treat a form of brain cancer, glioblastoma. This study is in the final stage of development that, if all goes well, culminates with application to the FDA to allow initiation of a clinical trial to test in people.
Dr. Ingrid Caras: That’s an interesting and valid question. There is a Phase 1 trial ongoing that is evaluating a novel type of stem/progenitor cell from the umbilical cord of healthy deliveries. In animal studies, these cells have been shown to reduce the toxic effects of chemotherapy and radiation and to speed up recovery. These cells are now being tested in a First-in-human clinical trial in patients who are undergoing high-dose chemotherapy to treat their disease.
There is a researcher at Stanford, Michelle Monje, who is investigating that the role of damage to stem cells in the cognitive problems that sometimes arise after chemo- and radiation therapy (“chemobrain”). It appears that damage to stem cells in the brain, especially those responsible for producing oligodendrocytes, contributes to chemobrain. In CIRM-funded work, Dr. Monje has identified small molecules that may help prevent or ameliorate the symptoms of chemobrain.
Is it possible to use a technique developed to fight one disease to also fight another? For instance, the bubble baby disease, which has cured (I think) more than 50 children, may also help fight sickle cell anemia? Don Reed.
Dr. Lisa Kadyk: Hi Don. Yes, the same general technique can often be applied to more than one disease, although it needs to be “customized” for each disease. In the example you cite, the technique is an “autologous gene-modified bone marrow transplant” – meaning the cells come from the patient themselves. This technique is relevant for single gene mutations that cause diseases of the blood (hematopoietic) system. For example, in the case of “bubble baby” diseases, a single mutation can cause failure of immune cell development, leaving the child unable to fight infections, hence the need to have them live in a sterile “bubble”. To cure that disease, blood stem cells, which normally reside in the bone marrow, are collected from the patient and then a normal version of the defective gene is introduced into the cells, where it is incorporated into the chromosomes. Then, the corrected stem cells are transplanted back into the patient’s body, where they can repopulate the blood system with cells expressing the normal copy of the gene, thus curing the disease.
A similar approach could be used to treat sickle cell disease, since it is also caused by a single gene mutation in a gene (beta hemoglobin) that is expressed in blood cells. The same technique would be used as I described for bubble baby disease but would differ in the gene that is introduced into the patient’s blood stem cells.
Is there any concern that CIRM’s lack of support in basic research will hamper the amount of new approaches that can reach clinical stages? Jason
Dr. Kelly Shepard: CIRM always has and continues to believe that basic research is vital to the field of regenerative medicine. Over the past 10 years CIRM has invested $904 million in “discovery stage/basic research”, and about $215 million in training grants that supported graduate students, post docs, clinical fellows, undergraduate, masters and high school students performing basic stem cell research. In the past couple of years, with only a limited amount of funds remaining, CIRM made a decision to invest most of the remaining funds into later stage projects, to support them through the difficult transition from bench to bedside. However, even now, CIRM continues to sponsor some basic research through its Bridges and SPARK Training Grant programs, where undergraduate, masters and even high school students are conducting stem cell research in world class stem cell laboratories, many of which are the same laboratories that were supported through CIRM basic research grants over the past 10 years. While basic stem cell research continues to receive a substantial level of support from the NIH ($1.8 billion in 2018, comprehensively on stem cell projects) and other funders, CIRM believes continued support for basic research, especially in key areas of stem cell research and vital opportunities, will always be important for discovering and developing new treatments.
What is the future of the use of crispr cas9 in clinical trials in california/globally. Art Venegas
Dr. Kelly Shepard: CRISPR/Cas9 is a powerful gene editing tool. In only a few years, CRISPR/Cas9 technology has taken the field by storm and there are already a few CRISPR/Cas9 based treatments being tested in clinical trials in the US. There are also several new treatments that are at the IND enabling stage of development, which is the final testing stage required by the FDA before a clinical trial can begin. Most of these clinical trials involving CRISPR go through an “ex vivo” approach, taking cells from the patient with a disease causing gene, correcting the gene in the laboratory using CRISPR, and reintroducing the cells carrying the corrected gene back into the patient for treatment. Sickle cell disease is a prime example of a therapy being developed using this strategy and CIRM funds two projects that are preparing for clinical trials with this approach. CRISPR is also being used to develop the next generation of cancer T-cell therapies (e.g. CAR-T), where T-cells – a vital part of our immune system – are modified to target and destroy cancer cell populations. Using CRISPR to edit cells directly in patients “in vivo” (inside the body) is far less common currently but is also being developed. It is important to note that any FDA sanctioned “in vivo” CRISPR clinical trial in people will only modify organ-specific cells where the benefits cannot be passed on to subsequent generations. There is a ban on funding for what are called germ line cells, where any changes could be passed down to future generations.
CIRM is currently supporting multiple CRISPR/Cas9 gene editing projects in California from the discovery or most basic stage of research, through the later stages before applying to test the technique in people in a clinical trial.
While the field is new – if early safety signals from the pioneering trials are good, we might expect a number of new CRISPR-based approaches to enter clinical testing over the next few years. The first of these will will likely be in the areas of bone marrow transplant to correct certain blood/immune or metabolic diseases, and cancer immunotherapies, as these types of approaches are the best studied and furthest along in the pipeline.
Explain the differences between gene therapy and stem cell therapy?Renee Konkol
Dr. Stephen Lin: Gene therapy is the direct modification of cells in a patient to treat a disease. Most gene therapies use modified, harmless viruses to deliver the gene into the patient. Gene therapy has recently seen many success in the clinic, with the first FDA approved therapy for a gene induced form of blindness in 2017 and other approvals for genetic forms of smooth muscle atrophy and amyloidosis.
Stem cell therapy is the introduction of stem cells into patients to treat a disease, usually with the purpose of replacing damaged or defective cells that contribute to the disease. Stem cell therapies can be derived from pluripotent cells that have the potential to turn into any cell in the body and are directed towards a specific organ lineage for the therapy. Stem cell therapies can also be derived from other cells, called progenitors, that have the ability to turn into a limited number of other cells in the body. for example hematopoietic or blood stem cells (HSCs), which are found in bone marrow, can turn into other cells of the blood system including B-cells and T-cells: while mesenchymal stem cells (MSCs), which are usually found in fat tissue, can turn into bone, cartilage, and fat cells. The source of these cells can be from the patient’s own body (autologous) or from another person (allogeneic).
Gene therapy is often used in combination with cell therapies when cells are taken from the patient and, in the lab, modified genetically to correct the mutation or to insert a correct form of the defective gene, before being returned to patients. Often referred to as “ex vivo gene therapy” – because the changes are made outside the patient’s body – these therapies include Chimeric Antigen Receptor T (CAR-T) cells for cancer therapy and gene modified HSCs to treat blood disorders such as severe combined immunodeficiency and sickle cell disease. This is an exciting area that has significantly improved and even cured many people already.
Currently, how can the outcome of CIRM stem cell medicine projects and clinical trials be soundly interpreted when their stem cell-specific doses are not known?James L. Sherley, M.D., Ph.D., Director. Asymmetrex, LLC
Dr. Stephen Lin: Stem cell therapies that receive approval to conduct clinical trials must submit a package of data to the FDA that includes studies that demonstrate their effectiveness, usually in animal models of the disease that the cell therapy is targeting. Those studies have data on the dose of the cell therapy that creates the therapeutic effect, which is used to estimate cell doses for the clinical trial. CIRM funds discovery and translational stage awards to conduct these types of studies to prepare cell therapies for clinical trials. The clinical trial is also often designed to test multiple doses of the cell therapy to determine the one that has the best therapeutic effect. Dosing can be very challenging with cell therapies because of issues including survival, engraftment, and immune rejection, but CIRM supports studies designed to provide data to give the best estimate possible.
Is there any research on using stem cells to increase the length of long bones in people?” For example, injecting stem cells into the growth plates to see if the cells can be used to lengthen limbs.Sajid
Dr. Kelly Shepard: There is quite a lot of ongoing research seeking ways to repair bones with stem cell based approaches, which is not the same but somewhat related. Much of this is geared towards repairing the types of bone injuries that do not heal well naturally on their own (large gaps, dead bone lesions, degenerative bone conditions). Also, a lot of this research involves engineering bone tissues in the lab and introducing the engineered tissue into a bone lesion that need be repaired. What occurs naturally at the growth plate is a complex interaction between many different cell types, much of which we do not fully understand. We do not fully understand how to use the cells that are used to engineer bone tissue in the lab. However, a group at Stanford, with some CIRM support, recently discovered a “skeletal stem cell” that exists naturally at the ends of human bones and at sites of fracture. These are quite different than MSCs and offer a new path to be explored for repairing and generating bone.
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.
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
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.