How regrowing tiny hairs could restore hearing loss

Man getting fitted with hearing aids

Hearing loss is something that affect tens of millions of Americans. Usually people notice those changes as they get older but the damage can be done years before that through the use of some prescription drugs or exposure to loud noise (I knew I shouldn’t have sat in the 6th row of that Led Zeppelin concert!)

Now researchers at the University of Southern California (USC) have identified the mechanism that appears to stop cells that are crucial to hearing from regenerating.

In a news release Dr. Neil Segil says this could, in theory, help reverse some hearing loss.  “Permanent hearing loss affects more than 60 percent of the population that reaches retirement age. Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”

The inner ear has two types of cells that are crucial for hearing; “hair cells” are sensory receptors and these help the brain detect sounds, and support cells that play, as the name implies, an important structural and supporting role for the hair cells.

In people, once the hair cells are damaged that’s it, you can’t repair or replace them and the resulting hearing loss is permanent. But mice, in the first few days of life, have ability to turn some of their support cells into hair cells, thus repairing any damage. So Segil and the team set out to identify how mice were able to do that and see if those lessons could be applied to people.

They identified specific proteins that played a key role in turning genes on and off, regulating if and when the support cells could turn into hair cells. They found that one molecule, H3K4mel, was particularly important in activating the correct genetic changes need to turn the support cells into hair cells. But in mice, levels of H3K4mel disappeared quickly after birth, so the team found a drug that helped preserve the molecule, meaning the support cells retained the ability to turn into hair cells.

Now, obviously because this was just done in mice there’s a lot more work that needs to be done to see if it can also work in people, but Segil says it’s certainly an encouraging and intriguing start.

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing. Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

The study is published in the journal Developmental Cell

CIRM has funded several projects targeting hearing loss. You can find them here.

CIRM funded trial for AMD shows promising results

This upcoming July is healthy vision month, a time to remember the importance of making vision and eye health a priority. It’s also a time to think about the approximately 12 million people, 40 and over in the United States, that have a vision impairment. Vision can be something that many of us take for granted, but losing even a portion of it can have a profound impact on our everyday life. It can impact your ability to do everyday things, from basic hygiene routines and driving to hobbies such as reading, writing, or watching a film.

It is because of this that CIRM has made vision related problems a priority, providing over $69 million in funding for six clinical trials related to vision loss. There is reason to be hopeful as these trials have demonstrated promising results. One of these trials, conducted by Regenerative Patch Technologies LLC (RPT), announced today results from its CIRM funded clinical trial ($16.3 million) for advanced, dry age-related macular degeneration (AMD).

AMD is a progressive disease resulting in death of the retinal pigment epithelium (RPE), an area of the eye that plays a key role in maintaining vision. Damage to the RPE causes distortion to central vision and eventually leads to legal blindness. Thanks to CIRM funding, RPT and scientists at the University of Southern California (USC) and UC Santa Barbara (UCSB) are growing specialized RPE cells from human embryonic stem cells (hESCs), placing them on a single layer scaffold, and implanting the combination device in the back of the eye to try to reverse the blindness caused by AMD.

One of the trial participants is Anna Kuehl, a USC alumna and avid nature lover. She was diagnosed with AMD in her mid 30s and gradually began losing the central vision in her left eye. Although her peripheral vision remained intact, she could no longer make out people’s faces clearly, drive a car, or read the time on her watch. This also meant she would have much more difficulty going on the nature hikes she enjoys so much. After receiving treatment, she noticed improvements in her vision.

Anna was not alone in these improvements post treatment. The implant, known as CPCB-RPE1, was delivered to the worst eye of 15 patients with AMD. All treated eyes were legally-blind having a best corrected visual acuity (BCVA) of 20/200 or worse (20/20 indicates perfect vision).

Patients in the clinical trial were assessed for visual function and the results were as follows:

  • At an average of 34 months post-implantation (range 12-48 months), 27% (4/15) showed a greater than 5 letter improvement in BCVA and 33% (5/15) remained stable with a BCVA within 5 letters of baseline value. The improvements ranged from 7-15 letters or 1-3 lines on an eye chart.
  • In contrast, BCVA in the fellow, untreated eye declined by more than 5 letters (range 8-21 letters or 1-4 lines on an eye chart) in 80% (12/15) of subjects. There was no improvement in BCVA in the untreated eye of any subject. 
  • The implant was delivered safely and remained stably in place throughout the trial.
  • Refinements to the implantation procedure during the trial further improved its efficiency and safety profile.

In a news release from RPT, Mark Humayun, M.D., Ph.D., founder and co-owner of RPT, Director of the USC Ginsburg Institute for Biomedical Therapeutics and Co-Director of the USC Roski Eye Institute, Keck Medicine of USC, had this to say about the trial results.

“The improvements in best corrected visual acuity observed in some eyes receiving the implant are very promising, especially considering the very late stage of their disease. Improvements in visual acuity are exceedingly rare in geographic atrophy as demonstrated by the large decline in vision in many of the untreated eyes which also had disease. There are currently no approved therapies for this level of advanced dry age-related macular degeneration”. 

The full presentation can be found on RPT’s website linked here.

Watch the video below to learn more about Anna’s story.

Sometimes a cold stare is a good thing

A retina of a patient with macular degeneration. (Photo credit: Paul Parker/SPL)

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in the elderly in the U.S. It’s estimated that some 11 million Americans could have some form of the disease, a number that is growing every year. So if you are going to develop a treatment for this condition, you need to make sure it can reach a lot of people easily. And that’s exactly what some CIRM-supported researchers are doing.

Let’s back up a little first. AMD is a degenerative condition where the macular, the small central portion of your retina, is slowly worn away. That’s crucial because the retina is the light-sensing nerve tissue at the back of your eye. At first you notice that your vision is getting blurry and it’s hard to read fine print or drive a car. As it progresses you develop dark, blurry areas in the center of your vision.

There are two kinds of AMD, a wet form and a dry form. The dry form is the most common, affecting 90% of patients. There is no cure and no effective treatment. But researchers at the University of Southern California (USC), the University of California Santa Barbara (UCSB) and a company called Regenerative Patch Technologies are developing a method that is looking promising.

They are using stem cells to grow retinal pigment epithelium (RPE) cells, the kind attacked by the disease, and putting them on a tiny synthetic scaffold which is then placed at the back of the eye. The hope is these RPE cells will help slow down the progression of the disease or even restore vision.

Early results from a CIRM-funded clinical trial are encouraging. Of the five patients enrolled in the Phase 1/2a trial, four maintained their vision in the treated eye, two showed improvement in the stability of their vision, and one patient had a 17-letter improvement in their vision on a reading chart. In addition, there were no serious side effects or unanticipated problems.

So now the team are taking this approach one step further. In a study published in Scientific Reports, they say they have developed a way to cryopreserve or freeze this cell and scaffold structure.

In a news release, Dr. Dennis Clegg of UCSB, says the frozen implants are comparable to the non-frozen ones and this technique will extend shelf life and enable on-demand distribution to distant clinical sites, increasing the number of patients able to benefit from such treatments.

“It’s a major advance in the development of cell therapies using a sheet of cells, or a monolayer of cells, because you can freeze them as the final product and ship them all over the world.”

Cool.

Remembering Eli Broad, philanthropist and stem cell champion

Eli Broad, Photo by Nancy Pastor

The world of stem cell research lost a good friend this weekend. Eli Broad, a generous supporter of science, education and the arts, passed away at the age of 87.

Eli came from humble origins, born in the Bronx to an immigrant father who worked as a house painter and a mother who was a seamstress. He went to Michigan State University, working a number of jobs to pay his way, including selling women’s shoes, working as a door-to-door salesman for garbage disposal units, and delivering rolls of film to be developed. He graduated in three years and then became the youngest person ever to pass the CPA exam in Michigan.

He started out as an accountant but quickly switched to housing and development and was a millionaire by the time he was 30. As his wealth grew so did his interest in using that money to support causes dear to him and his wife Edythe.

With the passage of Proposition 71 in 2004 Broad put up money to help create the Broad Stem Cell Centers at UCLA, UC San Francisco and the University of Southern California. Those three institutions became powerhouses in stem cell research and the work they do is a lasting legacy to the generosity of the Broads.

Rosa Dilani, histology core manager at the Eli and Edythe Broad CIRM Center, explains the lab’s function to Eli Broad after the Oct. 29 ribbon cutting of the new building. In the background are U.S. Rep. Lucille Roybal-Allard (in purple) and Bob Klein in gray suit.

“Science has lost one of its greatest philanthropic supporters,” says Jonathan Thomas, PhD, JD, Chair of the CIRM Board. ” Eli and Edye Broad set the table for decades of transformative work in stem cell and gene therapy through their enthusiastic support for Proposition 71 and funding at a critical time in the early days of regenerative medicine. Their recent additional generous contributions to USC, UCLA and UCSF helped to further advance that work.  Eli and Edye understood the critical role of science in making the world a better place.  Through these gifts and their enabling support of the Broad Institute with Harvard and MIT, they have left a lasting legacy in the advancement of medicine that cannot be overstated.”

Through the Broad Foundation he helped fund groundbreaking work not just in science but also education and the arts. Gerun Riley, President of the Broad Foundation says Eli was always interested in improving the lives of others.

“As a businessman Eli saw around corners, as a philanthropist he saw the problems in the world and tried to fix them, as a citizen he saw the possibility in our shared community, and as a husband, father, mentor and friend he saw the potential in each of us.”

Eli and Edythe Broad

Inspiring new documentary about stem cell research

Poster for the documentary “Ending Disease”

2020 has been, to say the very least, a difficult and challenging year for all of us. But while the focus of the world has, understandably, been on the coronavirus there was also some really promising advances in stem cell research. Those advances are captured in a great new documentary called Ending Disease.

The documentary is by Emmy award-winning filmmaker Joe Gantz. In it he follows ten people who are facing life-threatening or life-changing diseases and injuries and who turn to pioneering stem cell therapies for help.

It’s an inspiring documentary, one that reminds you of the real need for new treatments and the tremendous hope and promise of stem cell therapies. Here’s a look at a trailer for Ending Disease.

You can see an exclusive screening of Ending Disease on Friday, January 8th, 2021 at 5:00pm PST.

After the livestream, there will be a live Q&A session where former members of the successful Proposition 14 campaign team – which refunded CIRM with an additional $5.5 billion – will be joined by CIRM’s President and CEO Dr. Maria Millan, talking about what lies ahead for CIRM and the future of stem cell research.

To purchase a ticket, click here. It only costs $12 and 50% of the ticket sales proceeds will go to Americans for Cures to help them continue to advocate for the advancement of stem cell research, and more importantly, for the patients and families to whom stem cell research provides so much hope.

If you need any extra persuading that it’s something you should definitely put on our calendar, here’s a letter from the film maker Joe Gantz.

I am the director of the documentary Ending Disease: The Stem Cell, Anti-Cancer T-Cell, & Antibody Revolution In Medicine, a film that will help inform people about the progress that’s been made in this field and how people with their lives on the line are now able to benefit from these new regenerative therapies. 

I was granted unprecedented access to ten of the first generation of clinical trials using stem cell and regenerative medicine to treat and cure many of the most devastating diseases and conditions including: brain cancer, breast cancer, leukemia and lymphoma, HIV, repairing a broken spinal cord, retinitis pigmentosa and SCID. The results are truly inspiring.

This is personal for me.  After spending four years making this documentary, I was diagnosed with bladder cancer. Upon diagnosis, I immediately felt the same desperation as millions of families who are in search of a medical breakthrough. I understood, on a personal level, what the patients we followed in the film all knew: when you are diagnosed with a disease, there is a narrow window of time in which you can effectively seek a life-saving treatment or cure. If treatment becomes available outside of that window, then it is too late. However, Ending Disease shows that with continued support for regenerative medicine, we can create a near future in which one-time cures and highly mitigating therapies are available to patients for a whole host of diseases.

Best regards,

Joe

Exploring tough questions, looking for answers

COVID-19 and social and racial injustice are two of the biggest challenges facing the US right now. This Thursday, October 8th, we are holding a conversation that explores finding answers to both.

The CIRM Alpha Stem Cell Clinic Network Symposium is going to feature presentations about advances in stem cell and regenerative research, highlighting treatments that are already in the clinic and being offered to patients.

But we’re also going to dive a little deeper into the work we support, and use it to discuss two of the most pressing issues of the day.

One of the topics being featured is research into COVID-19. To date CIRM has funded 17 different projects, including three clinical trials. We’ll talk about how these are trying to find ways to help people infected with the virus, seeing if stem cells can help restore function to organs and tissues damaged by the virus, and if we can use stem cells to help develop safe and effective vaccines.

Immediately after that we are going to use COVID-19 as a way of exploring how the people most at risk of being infected and suffering serious consequences, are also the ones most likely to be left out of the research and have most trouble accessing treatments and vaccines.

Study after study highlights how racial and ethnic minorities are underrepresented in clinical trials and disproportionately affected by debilitating diseases. We have a responsibility to change that, to ensure that the underserved are given the same opportunity to take part in clinical trials as other communities.

How do we do that, how do we change a system that has resisted change for so long, how do we overcome the mistrust that has built up in underserved communities following decades of abuse? We’ll be talking about with experts who are on the front lines of this movement.

It promises to be a lively meeting. We’d love to see you there. It’s virtual – of course – it’s open to everyone, and it’s free.

Here’s where you can register and find out more about the Symposium

It’s all about the patients

Ronnie, born with a fatal immune disorder now leading a normal life thanks to a CIRM-funded stem cell/gene therapy: Photo courtesy of his mum Upasana

Whenever you are designing something new you always have to keep in mind who the end user is. You can make something that works perfectly fine for you, but if it doesn’t work for the end user, the people who are going to work with it day in and day out, you have been wasting your time. And their time too.

At CIRM our end users are the patients. Everything we do is about them. Starting with our mission statement: to accelerate stem cell treatments to patients with unmet medical needs. Everything we do, every decision we make, has to keep the needs of the patient in mind.

So, when we were planning our recent 2020 Grantee Meeting (with our great friends and co-hosts UC Irvine and UC San Diego) one of the things we wanted to make sure didn’t get lost in the mix was the face and the voice of the patients. Often big conferences like this are heavy on science with presentations from some of the leading researchers in the field. And we obviously wanted to make sure we had that element at the Grantee meeting. But we also wanted to make sure that the patient experience was front and center.

And we did just that. But more on that in a minute. First, let’s talk about why the voice of the patient is important.

Some years ago, Dr. David Higgins, a CIRM Board member and patient advocate for Parkinson’s Disease (PD), said that when researchers are talking about finding treatments for PD they often focus on the dyskinesia, the trembling and shaking and muscle problems. However, he said if you actually asked people with PD you’d find they were more concerned with other aspects of the disease, the insomnia, anxiety and depression among other things. The key is you have to ask.

Frances Saldana, a patient advocate for research into Huntington’s disease

So, we asked some of our patient advocates if they would be willing to be part of the Grantee Meeting. All of them, without hesitation, said yes. They included Frances Saldana, a mother who lost three of her children to Huntington’s disease; Kristin MacDonald, who lost her sight to a rare disorder but regained some vision thanks to a stem cell therapy and is hoping the same therapy will help restore some more; Pawash Priyank, whose son Ronnie was born with a fatal immune disorder but who, thanks to a stem cell/gene therapy treatment, is now healthy and leading a normal life.

Because of the pandemic everything was virtual, but it was no less compelling for that. We interviewed each of the patients or patient advocates beforehand and those videos kicked off each session. Hearing, and seeing, the patients and patient advocates tell their stories set the scene for what followed. It meant that the research the scientists talked about took on added significance. We now had faces and names to highlight the importance of the work the scientists were doing. We had human stories. And that gave a sense of urgency to the work the researchers were doing.

But that wasn’t all. After all the video presentations each session ended with a “live” panel discussion. And again, the patients and patient advocates were a key part of that. Because when scientists talk about taking their work into a clinical trial they need to know if the way they are setting up the trial is going to work for the patients they’re hoping to recruit. You can have the best scientists, the most promising therapy, but if you don’t design a clinical trial in a way that makes it easy for patients to be part of it you won’t be able to recruit or retain the people you need to test the therapy.

Patient voices count. Patient stories count.

But more than anything, hearing and seeing the people we are trying to help reminds us why we do this work. It’s so easy to get caught up in the day to day business of our jobs, struggling to get an experiment to work, racing to get a grant application in before the deadline. Sometimes we get so caught up in the minutiae of work we lose sight of why we are doing it. Or who we are doing it for.

At CIRM we have a saying; come to work every day as if lives depend on you, because lives depend on you. Listening to the voices of patients, seeing their faces, hearing their stories, reminds us not to waste a moment. Because lives depend on all of us.

Here’s one of the interviews that was featured at the event. I do apologize in advance for the interviewer, he’s rubbish at his job.

Meet the people who are changing the future

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.

CIRM & CZI & MOU for COVID-19

Too many acronyms? Not to worry. It is all perfectly clear in the news release we just sent out about this.

A new collaboration between the California Institute for Regenerative Medicine (CIRM) and the Chan Zuckerberg Initiative (CZI) will advance scientific efforts to respond to the COVID-19 pandemic by collaborating on disseminating single-cell research that scientists can use to better understand the SARS-CoV-2 virus and help develop treatments and cures.

CIRM and CZI have signed a Memorandum of Understanding (MOU) that will combine CIRM’s infrastructure and data collection and analysis tools with CZI’s technology expertise. It will enable CIRM researchers studying COVID-19 to easily share their data with the broader research community via CZI’s cellxgene tool, which allows scientists to explore and visualize measurements of how the virus impacts cell function at a single-cell level. CZI recently launched a new version of cellxgene and is supporting the single-cell biology community by sharing COVID-19 data, compiled by the global Human Cell Atlas effort and other related efforts, in an interactive and scalable way.

“We are pleased to be able to enter into this partnership with CZI,” said Dr. Maria T. Millan, CIRM’s President & CEO. “This MOU will allow us to leverage our respective investments in genomics science in the fight against COVID-19. CIRM has a long-standing commitment to generation and sharing of sequencing and genomic data from a wide variety of projects. That’s why we created the CIRM genomics award and invested in the Stem Cell Hub at the University of California, Santa Cruz, which will process the large complex datasets in this collaboration.”  

“Quickly sharing scientific data about COVID-19 is vital for researchers to build on each other’s work and accelerate progress towards understanding and treating a complex disease,” said CZI Single-Cell Biology Program Officer Jonah Cool. “We’re excited to partner with CIRM to help more researchers efficiently share and analyze single-cell data through CZI’s cellxgene platform.”

In March 2020, the CIRM Board approved $5 million in emergency funding to target COVID-19. To date, CIRM has funded 17 projects, some of which are studying how the SARS-CoV-2 virus impacts cell function at the single-cell level.

Three of CIRM’s early-stage COVID-19 research projects will plan to participate in this collaborative partnership by sharing data and analysis on cellxgene.   

  • Dr. Evan Snyder and his team at Sanford Burnham Prebys Medical Discovery Institute are using induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treating the virus.
  • Dr. Brigitte Gomperts at UCLA is studying a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19.
  • Dr. Justin Ichida at the University of Southern California is trying to determine if a drug called a kinase inhibitor can protect stem cells in the lungs and other organs, which the novel coronavirus selectively infects and kills.

“Cumulative data into how SARS-CoV-2 affects people is so powerful to fight the COVID-19 pandemic,” said Stephen Lin, PhD, the Senior CIRM Science Officer who helped develop the MOU. “We are grateful that the researchers are committed to sharing their genomic data with other researchers to help advance the field and improve our understanding of the virus.”

CZI also supports five distinct projects studying how COVID-19 progresses in patients at the level of individual cells and tissues. This work will generate some of the first single-cell biology datasets from donors infected by SARS-CoV-2 and provide critical insights into how the virus infects humans, which cell types are involved, and how the disease progresses. All data generated by these grants will quickly be made available to the scientific community via open access datasets and portals, including CZI’s cellxgene tool.

Stem Cell All-Stars, All For You

goldstein-larry

Dr. Larry Goldstein, UC San Diego

It’s not often you get a chance to hear some of the brightest minds around talk about their stem cell research and what it could mean for you, me and everyone else. That’s why we’re delighted to be bringing some of the sharpest tools in the stem cell shed together in one – virtual – place for our CIRM 2020 Grantee Meeting.

The event is Monday September 14th and Tuesday September 15th. It’s open to anyone who wants to attend and, of course, it’s all being held online so you can watch from the comfort of your own living room, or garden, or wherever you like. And, of course, it’s free.

BotaDaniela2261

Dr. Daniela Bota, UC Irvine

The list of speakers is a Who’s Who of researchers that CIRM has funded and who also happen to be among the leaders in the field. Not surprising as California is a global center for regenerative medicine. And you will of course be able to post questions for them to answer.

srivastava-deepak

Dr. Deepak Srivastava, Gladstone Institutes

The key speakers include:

Larry Goldstein: the founder and director of the UCSD Stem Cell Program talking about Alzheimer’s research

Irv Weissman: Stanford University talking about anti-cancer therapies

Daniela Bota: UC Irvine talking about COVID-19 research

Deepak Srivastava: Gladsone Institutes, talking about heart stem cells

Other topics include the latest stem cell approaches to COVID-19, spinal cord injury, blindness, Parkinson’s disease, immune disorders, spina bifida and other pediatric disorders.

You can choose one topic or come both days for all the sessions. To see the agenda for each day click here. Just one side note, this is still a work in progress so some of the sessions have not been finalized yet.

And when you are ready to register go to our Eventbrite page. It’s simple, it’s fast and it will guarantee you’ll be able to be part of this event.

We look forward to seeing you there.