Advocating for Huntington’s Disease: Daniel Medina’s Journey

Daniel Medina

In honor of Huntington’s Disease (HD) Awareness Month, we’re featuring a guest blog by HD patient advocate Daniel Medina. Daniel became actively involved in the HD community when he learned that his younger brother was at risk for inheriting this devastating neurodegenerative disease. Since then he has been a champion for HD awareness by organizing HD patient support groups and walks in southern California and serving on the Board of HD Care, UC Irvine’s non-profit HD support group. 


Guest Blog by Daniel Medina

A visit to a care home back in April of 2012 changed my life forever. It all started when my mother took my 14-year-old half-brother to meet his grandfather for the very first time. My brother’s aunt led the way to what seemed to be an emotional, long overdue family encounter.  As they walked into his room they were impacted by what they saw.

They saw an elderly, bedridden gentleman that suffered from uncontrollable body movements. He was unable to communicate and was totally dependent on others. As the tears flowed, so did my mom’s sense of urgency to find out the name of his affliction. That’s when the words “Huntington’s disease” were uttered by my brother’s aunt. Her knowledge was limited to sharing that it was a genetic disease.

I immediately began my own research as the details of this encounter were relayed to me. My curiosity soon turned into despair and anguish as I learned that my brother was at risk of being a carrier of this horrible neurodegenerative disease.  I felt empowered as I began attending HD fundraising events. There I met so many courageous families that clung to the hope of a better tomorrow.  This hope came through the possibility of scientists working towards finding a treatment or a cure through stem cell research.

As of 2013 my role had evolved from an event attendee to a patient advocate. It became clear to me that there was an immediate need to fill voids that were unattended. In 2014, I started an HD support group in my area in order to tend to the needs of the HD community. The appreciation and gratitude I felt made every second I invested very much worthwhile.

In the last three years, we have seen the tremendous impact and growth HD organizations like Help4HD International, HD CARE and WeHaveAFace, have had on a local and global scale. It has been such an honor and a privilege to work alongside them. Our collaborative efforts have had a ripple effect of amazing results. The success of one is the success of all.

At the beginning of 2015, I was introduced to Americans for Cures. Working to promote and educate the public about the benefits of stem cell stem research was a perfect fit. Meeting advocates from other disease communities has educated me and taught me how our common goals towards finding cures unites us.

My HD Advocacy journey began with a simple visit to a care home. In a matter of a few years, it has transformed into a life mission to help those suffering the effects of this terrible disease.

2016 HD-CARE Conference. Patient Advocates Ron Shapiro, Adrienne Shapiro, David Saldana, Frances Saldana, Daniel Medina with Karen Ring from CIRM.

Stem Cell Stories That Caught Our Eye: Free Patient Advocate Event in San Diego, and new clues on how to fix muscular dystrophy and Huntington’s disease

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Stem cell research is advancing so fast that it’s sometimes hard to keep up. That’s one of the reasons we have our Friday roundup, to let you know about some fascinating research that came across our desk during the week that you might otherwise have missed.

Of course, another way to keep up with the latest in stem cell research is to join us for our free Patient Advocate Event at UC San Diego next Thursday, April 20th from 12-1pm.  We are going to talk about the progress being made in stem cell research, the problems we still face and need help in overcoming, and the prospects for the future.

We have four great speakers:

  • Catriona Jamieson, Director of the CIRM UC San Diego Alpha Stem Cell Clinic and an expert on cancers of the blood
  • Jonathan Thomas, PhD, JD, Chair of CIRM’s Board
  • Jennifer Briggs Braswell, Executive Director of the Sanford Stem Cell Clinical Center
  • David Higgins, Patient Advocate for Parkinson’s on the CIRM Board

We will give updates on the exciting work taking place at UCSD and the work that CIRM is funding. We have also set aside some time to get your thoughts on how we can improve the way we work and, of course, answer your questions.

What: Stem Cell Therapies and You: A Special Patient Advocate Event

When: Thursday, April 20th 12-1pm

Where: The Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Why: Because the people of California have a right to know how their money is helping change the face of regenerative medicine

Who: This event is FREE and open to everyone.

We have set up an EventBrite page for you to RSVP and let us know if you are coming. And, of course, feel free to share this with anyone you think might be interested.

This is the first of a series of similar Patient Advocate Update meetings we plan on holding around California this year. We’ll have news on other locations and dates shortly.

 

Fixing a mutation that causes muscular dystrophy (Karen Ring)

It’s easy to take things for granted. Take your muscles for instance. How often do you think about them? (Don’t answer this if you’re a body builder). Daily? Monthly? I honestly don’t think much about my muscles unless I’ve injured them or if they’re sore from working out.

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Heart muscle cells (green) that don’t have dystrophin protein (Photo; UT Southwestern)

But there are people in this world who think about their muscles or their lack of them every day. They are patients with a muscle wasting disease called Duchenne muscular dystrophy (DMD). It’s the most common type of muscular dystrophy, and it affects mainly young boys – causing their muscles to progressively weaken to the point where they cannot walk or breathe on their own.

DMD is caused by mutations in the dystrophin gene. These mutations prevent muscle cells from making dystrophin protein, which is essential for maintaining muscle structure. Scientists are using gene editing technologies to find and fix these mutations in hopes of curing patients of DMD.

Last year, we blogged about a few of these studies where different teams of scientists corrected dystrophin mutations using CRISPR/Cas9 gene editing technology in human cells and in mice with DMD. One of these teams has recently followed up with a new study that builds upon these earlier findings.

Scientists from UT Southwestern are using an alternative form of the CRISPR gene editing complex to fix dystrophin mutations in both human cells and mice. This alternative CRISPR complex makes use of a different cutting enzyme, Cpf1, in place of the more traditionally used Cas9 protein. It’s a smaller protein that the scientists say can get into muscle cells more easily. Cpf1 also differs from Cas9 in what DNA nucleotide sequences it recognizes and latches onto, making it a new tool in the gene editing toolbox for scientists targeting DMD mutations.

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Gene-edited heart muscle cells (green) that now express dystrophin protein (Photo: UT Southwestern)

Using CRISPR/Cpf1, the scientists corrected the most commonly found dystrophin mutation in human induced pluripotent stem cells derived from DMD patients. They matured these corrected stem cells into heart muscle cells in the lab and found that they expressed the dystrophin protein and functioned like normal heart cells in a dish. CRISPR/Cpf1 also corrected mutations in DMD mice, which rescued dystrophin expression in their muscle tissues and some of the muscle wasting symptoms caused by the disease.

Because the dystrophin gene is one of the longest genes in our genome, it has more locations where DMD-causing mutations could occur. The scientists behind this study believe that CRISPR/Cpf1 offers a more flexible tool for targeting different dystrophin mutations and could potentially be used to develop an effective gene therapy for DMD.

Senior author on the study, Dr. Eric Olson, provided this conclusion about their research in a news release by EurekAlert:

“CRISPR-Cpf1 gene-editing can be applied to a vast number of mutations in the dystrophin gene. Our goal is to permanently correct the underlying genetic causes of this terrible disease, and this research brings us closer to realizing that end.”

 

A cellular traffic jam is the culprit behind Huntington’s disease (Todd Dubnicoff)

Back in the 1983, the scientific community cheered the first ever mapping of a genetic disease to a specific area on a human chromosome which led to the isolation of the disease gene in 1993. That disease was Huntington’s, an inherited neurodegenerative disorder that typically strikes in a person’s thirties and leads to death about 10 to 15 years later. Because no effective therapy existed for the disease, this discovery of Huntingtin, as the gene was named, was seen as a critical step toward a better understand of Huntington’s and an eventual cure.

But flash forward to 2017 and researchers are still foggy on how mutations in the Huntingtin gene cause Huntington’s. New research, funded in part by CIRM, promises to clear some things up. The report, published this week in Neuron, establishes a connection between mutant Huntingtin and its impact on the transport of cell components between the nucleus and cytoplasm.

Roundup Picture1

The pores in the nuclear envelope allows proteins and molecules to pass between a cell’s nucleus and it’s cytoplasm. Image: Blausen.com staff (2014).

To function smoothly, a cell must be able to transport proteins and molecules in and out of the nucleus through holes called nuclear pores. The research team – a collaboration of scientists from Johns Hopkins University, the University of Florida and UC Irvine – found that in nerve cells, the mutant Huntingtin protein clumps up and plays havoc on the nuclear pore structure which leads to cell death. The study was performed in fly and mouse models of HD, in human HD brain samples as well as HD patient nerve cells derived with the induced pluripotent stem cell technique – all with this same finding.

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Huntington’s disease is caused by the loss of a nerve cells called medium spiny neurons. Image: Wikimedia commons

By artificially producing more of the proteins that make up the nuclear pores, the damaging effects caused by the mutant Huntingtin protein were reduced. Similar results were seen using drugs that help stabilize the nuclear pore structure. The implications of these results did not escape George Yohrling, a senior director at the Huntington’s Disease Society of America, who was not involved in the study. Yohrling told Baltimore Sun reporter Meredith Cohn:

“This is very exciting research because we didn’t know what mutant genes or proteins were doing in the body, and this points to new areas to target research. Scientists, biotech companies and pharmaceutical companies could capitalize on this and maybe develop therapies for this biological process”,

It’s important to temper that excitement with a reality check on how much work is still needed before the thought of clinical trials can begin. Researchers still don’t understand why the mutant protein only affects a specific type of nerve cells and it’s far from clear if these drugs would work or be safe to use in the context of the human brain.

Still, each new insight is one step in the march toward a cure.

Stem cells reveal developmental defects in Huntington’s disease

Three letters, C-A-G, can make the difference between being healthy and having a genetic brain disorder called Huntington’s disease (HD). HD is a progressive neurodegenerative disease that affects movement, cognition and personality. Currently more than 30,000 Americans have HD and there is no cure or treatment to stop the disease from progressing.

A genetic mutation in the huntingtin gene. caused by an expanded repeat of CAG nucleotides, the building blocks of DNA that make our genes, is responsible for causing HD. Normal people have less than 26 CAG repeats while those with 40 or more repeats will get HD. The reasons are still unknown why this trinucleotide expansion causes the disease, but scientists hypothesize that the extra CAG copies in the huntingtin gene produce a mutant version of the Huntingtin protein, one that doesn’t function the way the normal protein should.

The HD mutation causes neurodegeneration.

As with many diseases, things start to go wrong in the body long before symptoms of the disease reveal themselves. This is the case for HD, where symptoms typically manifest in patients between the ages of 30 and 50 but problems at the molecular and cellular level occur decades before. Because of this, scientists are generating new models of HD to unravel the mechanisms that cause this disease early on in development.

Induced pluripotent stem cells (iPSCs) derived from HD patients with expanded CAG repeats are an example of a cell-based model that scientists are using to understand how HD affects brain development. In a CIRM-funded study published today in the journal Nature Neuroscience, scientists from the HD iPSC Consortium used HD iPSCs to study how the HD mutation causes problems with neurodevelopment.

They analyzed neural cells made from HD patient iPSCs and looked at what genes displayed abnormal activity compared to healthy neural cells. Using a technique called RNA-seq analysis, they found that many of these “altered” genes in HD cells played important roles in the development and maturation of neurons, the nerve cells in the brain. They also observed differences in the structure of HD neurons compared to healthy neurons when grown in a lab. These findings suggest that HD patients likely have problems with neurodevelopment and adult neurogenesis, the process where the adult stem cells in your brain generate new neurons and other brain cells.

After pinpointing the gene networks that were altered in HD neurons, they identified a small molecule drug called isoxazole-9 (Isx-9) that specifically targets these networks and rescues some of the HD-related symptoms they observed in these neurons. They also tested Isx-9 in a mouse model of HD and found that the drug improved their cognition and other symptoms related to impaired neurogenesis.

The authors conclude from their findings that the HD mutation disrupts gene networks that affect neurodevelopment and neurogenesis. These networks can be targeted by Isx-9, which rescues HD symptoms and improves the mental capacity of HD mice, suggesting that future treatments for HD should focus on targeting these early stage events.

I reached out to the leading authors of this study to gain more insights into their work. Below is a short interview with Dr. Leslie Thompson from UC Irvine, Dr. Clive Svendsen from Cedars-Sinai, and Dr. Steven Finkbeiner from the Gladstone Institutes. The responses were mutually contributed.

Leslie Thompson

Steven Finkbeiner

Clive Svendsen

 

 

 

 

 

 Q: What is the mission of the HD iPSC Consortium?

To create a resource for the HD community of HD derived stem cell lines as well as tackling problems that would be difficult to do by any lab on its own.  Through the diverse expertise represented by the consortium members, we have been able to carry out deep and broad analyses of HD-associated phenotypes [observable characteristics derived from your genome].  The authorship of the paper  – the HD iPSC consortium (and of the previous consortium paper in 2012) – reflects this goal of enabling a consortium and giving recognition to the individuals who are part of it.

Q: What is the significance of the findings in your study and what novel insights does it bring to the HD field?

 Our data revealed a surprising neurodevelopmental effect of highly expanded repeats on the HD neural cells.  A third of the changes reflected changes in networks that regulate development and maturation of neurons and when compared to neurodevelopment pathways in mice, showed that maturation appeared to be impacted.  We think that the significance is that there may be very early changes in HD brain that may contribute to later vulnerability of the brain due to the HD mutation.  This is compounded by the inability to mount normal adult neurogenesis or formation of new neurons which could compensate for the effects of mutant HTT.  The genetic mutation is present from birth and with differentiated iPSCs, we are picking up signals earlier than we expected that may reflect alterations that create increased susceptibility or limited homeostatic reserves, so with the passage of time, symptoms do result.

What we find encouraging is that using a small molecule that targets the pathways that came out of the analysis, we protected against the impact of the HD mutation, even after differentiation of the cells or in an adult mouse that had had the mutation present throughout its development.

Q: There’s a lot of evidence suggesting defects in neurodevelopment and neurogenesis cause HD. How does your study add to this idea?

Agree completely that there are a number of cell, mouse and human studies that suggest that there are problems with neurodevelopment and neurogenesis in HD.  Our study adds to this by defining some of the specific networks that may be regulating these effects so that drugs can be developed around them.  Isx9, which was used to target these pathways specifically, shows that even with these early changes, one can potentially alleviate the effects. In many of the assays, the cells were already through the early neurodevelopmental stages and therefore would have the deficits present.  But they could still be rescued.

Q: Has Isx-9 been used previously in cell or animal models of HD or other neurodegenerative diseases? Could it help HD patients who already are symptomatic?

The compound has not been used that we know of in animal models to treat neurodegeneration, although was shown to affect neurogenesis and memory in mice. Isx9 was used in a study by Stuart Lipton in Parkinson’s iPSC-derived neurons in one study and it had a protective effect on apoptosis [cell death] in a study by Ryan SD et al., 2013, Cell.

We think this type of compound could help patients who are symptomatic.  Isx-9 itself is a fairly pleiotropic drug [having multiple effects] and more research would be needed [to test its safety and efficacy].

Q: Have you treated HD mice with Isx-9 during early development to see whether the molecule improves HD symptoms?

Not yet, but we would like to.

Q: What are your next steps following this study and do you have plans to translate this research into humans?

We are following up on the research in more mature HD neurons and to determine at what stages one can rescue the HD phenotypes in mice.  Also, we would need to do pharmacodynamics and other types of assays in preclinical models to assess efficacy and then could envision going into human trials with a better characterized drug.  Our goal is to ultimately translate this to human treatments in general and specifically by targeting these altered pathways.

A ‘Call to Action’ for change at the FDA

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It’s bad enough to have to battle a debilitating and ultimately deadly disease like Huntington’s disease (HD). But it becomes doubly difficult and frustrating when you feel that the best efforts to develop a therapy for HD are running into a brick wall.

That’s how patients and patient advocates working on HD feel as they see the Food and Drug Administration (FDA) throw up what they feel are unnecessary obstacles in the way of promising research.

So the group Help 4HD International has decided to push back, launching an online campaign to get its supporters to pressure the FDA into taking action. Any action.

Posing the question “Does the FDA understand that time is something we simply don’t have?” Help 4HD is urging people to write to the FDA:

“We have heard the FDA say they feel like our loved ones have quality of life at the end stages of HD. We have heard them say people with HD get to live for 20 years after diagnosis. It seems like the FDA doesn’t understand what we are having to live with generation after generation. We have seen HD research die because the researcher couldn’t get an IND (Investigational New Drug, or approval to put a new drug into clinical trials) from the FDA. We have seen trials that should be happening here in the USA move to other countries because of this. We have seen the FDA continue to put up delays and roadblocks. We are lucky to have amazing research going on for HD/JHD (juvenile HD) right now, but what is that research worth if the FDA doesn’t let it go into clinical trials? Drug development is a business and costs millions of dollars. If the FDA continues to refuse INDs, the fear is that companies will stop investing in HD research. This is a fate that we can’t let happen! We need to write to the FDA and let them know our frustrations and also help them understand our disease better.”

The group has drafted a sample letter for people to use or adapt as they see fit. They’ve even provided them with the address to mail the letter to. In short, they are making it as easy as possible to get as many people as possible to write to the FDA and ask for help.

The HD community is certainly not the only one frustrated at the FDA’s  glacial pace of approval of for clinical trials. That frustration is one of many reasons why Congress passed the 21st Century Cures Act late last year. That’s also the reason why we started our Stem Cell Champions campaign, to get the FDA to create a more efficient, but no less safe, approval process.

Several of our most active Stem Cell Champions – like Frances Saldana, Judy Roberson and Katie Jackson – are members of the HD Community. Last May several members of the CIRM Team attended the HD-Care Conference, held to raise awareness about the unmet medical needs of this community. We blogged about it here.

While this call to action comes from the HD community it may serve as a template for other organizations and communities. Many have the same frustrations at the slow pace of approval of therapies for clinical trials.

We are hoping the 21st Century Cures Act will lead to the desired changes at the FDA. But until we see proof that’s the case we understand and support the sense of urgency that the HD community has. They don’t have the luxury of time.

 

 

Using stem cells to fix bad behavior in the brain

 

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Gladstone Institutes Steven Finkbeiner and Gaia Skibinski: Photo courtesy Chris Goodfellow, Gladstone Institutes

Diseases of the brain have many different names, from Alzheimer’s and Parkinson’s to ALS and Huntington’s, but they often have similar causes. Researchers at the Gladstone Institutes in San Francisco are using that knowledge to try and find an approach that might be effective against all of these diseases. In a new CIRM-funded study, they have identified one protein that could help do just that.

Many neurodegenerative diseases are caused by faulty proteins, which start to pile up and cause damage to neurons, the brain cells that are responsible for processing and transmitting information. Ultimately, the misbehaving proteins cause those cells to die.

The researchers at the Gladstone found a way to counter this destructive process by using a protein called Nrf2. They used neurons from humans (made from induced pluripotent stem cells – iPSCs – hence the stem cell connection here) and rats. They then tested these cells in neurons that were engineered to have two different kinds of mutations found in  Parkinson’s disease (PD) plus the Nrf2 protein.

Using a unique microscope they designed especially for this study, they were able to track those transplanted neurons and monitor what happened to them over the course of a week.

The neurons that expressed Nrf2 were able to render one of those PD-causing proteins harmless, and remove the other two mutant proteins from the brain cells.

In a news release to accompany the study in The Proceedings of the National Academy of Sciences, first author Gaia Skibinski, said Nrf2 acts like a house-cleaner brought in to tidy up a mess:

“Nrf2 coordinates a whole program of gene expression, but we didn’t know how important it was for regulating protein levels until now. Over-expressing Nrf2 in cellular models of Parkinson’s disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we’ve found.”

Steven Finkbeiner, the senior author on the study and a Gladstone professor, said this model doesn’t just hold out hope for treating Parkinson’s disease but for treating a number of other neurodegenerative problems:

“I am very enthusiastic about this strategy for treating neurodegenerative diseases. We’ve tested Nrf2 in models of Huntington’s disease, Parkinson’s disease, and ALS, and it is the most protective thing we’ve ever found. Based on the magnitude and the breadth of the effect, we really want to understand Nrf2 and its role in protein regulation better.”

The next step is to use this deeper understanding to identify other proteins that interact with Nrf2, and potentially find ways to harness that knowledge for new therapies for neurodegenerative disorders.

Advancing Stem Cell Research at the CIRM Bridges Conference

Where will stem cell research be in 10 years?

What would you say to patients who wanted stem cell therapies now?

What are the most promising applications for stem cell research?

Why is it important for the government to fund regenerative medicine?

These challenging and thought-provoking questions were posed to a vibrant group of undergraduate and masters-level students at this year’s CIRM Bridges to Stem Cell Research and Therapy conference.

Educating the next generation of stem cell scientists

The Bridges program is one of CIRM’s educational programs that offers students the opportunity to take coursework at California state schools and community colleges and conduct stem cell research at top universities and industry labs. Its goal is to train the next generation of stem cell scientists by giving them access to the training and skills necessary to succeed in this career path.

The Bridges conference is the highlight of the program and the culmination of the students’ achievements. It’s a chance for students to showcase the research projects they’ve been working on for the past year, and also for them to network with other students and scientists.

Bridges students participated in a networking pitch event about stem cell research.

Bridges students participated in a networking pitch event about stem cell research.

CIRM kicked off the conference with a quick and dirty “Stem Cell Pitch” networking event. Students were divided into groups, given one of the four questions above and tasked with developing a thirty second pitch that answered their question. They were only given ten minutes to introduce themselves, discuss the question, and pick a spokesperson, yet when each team’s speaker took the stage, it seemed like they were practiced veterans. Every team had a unique, thoughtful answer that was inspiring to both the students and to the other scientists in the crowd.

Getting to the clinic and into patients

The bulk of the Bridges conference featured student poster presentations and scientific talks by leading academic and industry scientists. The theme of the talks was getting stem cell research into the clinic and into patients with unmet medical needs.

Here are a few highlights and photos from the talks:

On the clinical track for Huntington’s disease

Leslie Thompson, Professor at UC Irvine, spoke about her latest research in Huntington’s disease (HD). She described her work as a “race against time.” HD is a progressive neurodegenerative disorder that’s associated with multiple social and physical problems and currently has no cure. Leslie described how her lab is heading towards the clinic with human embryonic stem cell-derived neural (brain) stem cells that they are transplanting into mouse models of HD. So far, they’ve observed positive effects in HD mice that received human neural stem cell transplants including an improvement in the behavioral and motor defects and a reduction in the accumulation of toxic mutant Huntington protein in their nerve cells.

Leslie Thompson

Leslie Thompson

Leslie noted that because the transplanted stem cells are GMP-grade (meaning their quality is suitable for use in humans), they have a clear path forward to testing their potential disease modifying activity in human clinical trials. But before her team gets to humans, they must take the proper regulatory steps with the US Food and Drug Administration and conduct further experiments to test the safety and proper dosage of their stem cells in other mouse models as well as test other potential GMP-grade stem cell lines.

Gene therapy for SCID babies

Morton Cowan, a pediatric immunologist from UC San Francisco, followed Leslie with a talk about his efforts to get gene therapy for SCID (severe combined immunodeficiency disease) off the bench into the clinic. SCID is also known as bubble-baby disease and put simply, is caused by a lack of a functioning immune system. SCID babies don’t have normal T and B immune cell function and as a result, they generally die of infection or other conditions within their first year of life.

Morton Cowan

Morton Cowan, UCSF

Morton described how the gold standard treatment for SCID, which is hematopoietic or blood stem cell transplantation, is only safe and effective when the patient has an HLA matched sibling donor. Unfortunately, many patients don’t have this option and face life-threatening challenges of transplant rejection (graft-versus host disease). To combat this issue, Morton and his team are using gene therapy to genetically correct the blood stem cells of SCID patients and transplant those cells back into these patients so that they can generate healthy immune cells.

They are currently developing a gene therapy for a particularly hard-to-treat form of SCID that involves deficiency in a protein called Artemis, which is essential for the development of the immune system and for repairing DNA damage in cells. Currently his group is conducting the necessary preclinical work to start a gene therapy clinical trial for children with Artemis-SCID.

Treating spinal cord injury in the clinic

Casey Case, Asterias Biotherapeutics

Casey Case, Asterias Biotherapeutics

Casey Case, Senior VP of Research and Nonclinical Development at Asterias Biotherapeutics, gave an update on the CIRM-funded clinical trial for cervical (neck) spinal cord injury (SCI). They are currently testing the safety of transplanting different doses of their oligodendrocyte progenitor cells (AST-OPC1) in a group of SCI patients. The endpoint for this trial is an improvement in movement greater than two motor levels, which would offer a significant improvement in a patient’s ability to do some things on their own and reduce the cost of their healthcare. You can read more about these results and the ongoing study in our recent blogs (here, here).

Opinion: Scientists should be patient advocates

David Higgins gave the most moving speech of the day. He is a Parkinson’s patient and the Patient Advocate on the CIRM board and he spoke about what patient advocates are and how to become one. David explained how, these days, drug development and patient advocacy is more patient oriented and patients are involved at the center of every decision whether it be questions related to how a drug is developed, what side effects should be tolerated, or what risks are worth taking. He also encouraged the Bridges students to become patient advocates and understand what their needs are by asking them.

David Higgins, Parkinson's advocate and CIRM Board member

David Higgins

“As a scientist or clinician, you need to be an ambassador. You have a job of translating science, which is a foreign language to most people, and you can all effectively communicate to a lay audience without being condescending. It’s important to understand what patients’ needs are, and you’ll only know that if you ask them. Patients have amazing insights into what needs to be done to develop new treatments.”

Bridging the gap between research and patients

The Bridges conference is still ongoing with more poster presentations, a career panel, and scientific talks on discovery and translational stem cell research and commercializing stem cell therapies to all patients in need. It truly is a once in a lifetime opportunity for the Bridges students, many of whom are considering careers in science and regenerative medicine and are taking advantage of the opportunity to talk and network with prominent scientists.

If you’re interested in hearing more about the Bridges conference, follow us on twitter (@CIRMnews, @DrKarenRing, #CIRMBridges2016) and on Instagram (@CIRM_Stemcells).

On the Hunt for Huntington’s Disease Treatments in the New Millennium

“Over the next five to ten years, we want to make Huntington’s disease an increasingly treatable condition.”

This bold and inspiring statement was made by Dr. Ray Dorsey at the inaugural HD-CARE symposium for Huntington’s disease (HD) research held at UC Irvine last month. The event brought together scientists, doctors, patients, family members, and caregivers to discuss the latest discoveries in HD research and to talk openly about how we can address the unmet needs of patients suffering from this terrible, deadly neurodegenerative disease.

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Symposium speakers and HD-CARE Board Members

The symposium was hosted by HD-CARE, a non-profit organization established three years ago to support HD research and patient care. Frances Saldaña, HD-CARE president and a CIRM patient advocate, established this symposium with the goal of bringing new hope to HD patients and their family members.

Frances Saldana, HD-CARE President & Patient Advocate

Frances Saldana

“There is so much exciting research taking place all over the world that one can hardly contain oneself with excitement and hope,” explained Saldaña. “It is only right to share this scientific information and breakthroughs in HD research that has undoubtedly given our families so much hope.”

Recent breakthroughs

The symposium featured talks by scientists and doctors that spanned a broad range of topics including the recent progress of using human stem cells to model HD, the hope and hype of gene editing, and the benefits of in vitro fertilization (IVF) for HD families.

Dr. Ray Dorsey, Professor at the University of Rochester Medical Center, gave the keynote address. Inspiring from the start, he captured the audience’s attention by posing the question, “Why are we here?” To which he answered, “I think we are here to change this sign, which says Huntington’s disease is a fatal genetic neurodegenerative disease, to one that says HD is an increasingly treatable condition. Over the next five to ten years, we want to make HD an increasingly treatable condition.”

Referencing the HIV epidemic in the 1980s, Dorsey pointed out that there is precedent. What was thought to be a disease with a rapid death sentence is now, decades later, a treatable condition, and his belief is that the same can be done for HD patients in the near future.

Dorsey next highlighted major clinical advances in HD treatment including a record ten drugs currently in development in 2016. Treatments that he felt had particular promise included a gene silencing therapy by Ionis Pharmaceuticals, which is the first treatment being tested in clinical trials that targets the cause of HD. Dorsey also mentioned two drugs, Pridopidine and SD-809 (a modified version of the FDA-approved drug Tetrabenazine), that are used to treat symptoms of HD.

My favorite part of the talk was the end where he described his latest efforts to develop digital biomarkers that use smart phones and wearables to monitor a patient’s response to HD treatments in their own home.  This technology will not only make it easier to determine which treatments are effective for HD, but will also improve the quality of care patients receive during clinical trials.

Dr. Ray Dorsey

Dr. Ray Dorsey

“We think that these devices, which allow us to make assessments of how people are doing with a given condition, will soon be able to connect patients to clinicians so they can receive care regardless of who they are or where they live. We hope that for Huntington’s disease, these tools and technologies will enable us to connect patients to effective treatments for HD.”

Battle cry for change

While the science at the symposium was certainly encouraging, the voices of the patients and patient advocates made the strongest impression. Many of them spoke out to share their stories or ask questions. Others, like Saldaña, advocated for faster progress towards a cure.

“This disease is one in which family members and friends need to rally together and demand that research be properly funded to end this generational disease.  It is not one in which policy makers can sit around and wonder if they should fund it…it is a five-alarm fire that needs immediate action, and from the families, a fierce battle cry asking from policy makers and decision makers to fund aggressive research to end Huntington’s disease.”

Julie Rosling, Frances Saldana,

Julie Rosling receives the Patient Advocacy Award from HD-CARE’s Frances Saldana and Karen Thornburn

A particularly moving event was the presentation of the 2016 Patient Advocacy Award to Julie Rosling. Members of the HD-CARE board presented Rosling with a trophy to honor her brave efforts in advocating for HD patient rights. Saldaña described how Rosling was fearless at a HD patient-focused drug development meeting with the FDA in DC last fall. Along with other patients, she stood up and challenged the FDA to move HD into the fast track category for approving clinical trials.

A similar demand for regulatory change was brought up during the symposium regarding the approval of stem cell treatments for HD. As the representative for CIRM, I had a few moments to talk about our new Stem Cell Champions campaign, which is actively recruiting patient advocates that can work with us to help make the FDA approval process for stem cell treatments faster and more efficient. Our colleagues at Americans for Cures also spoke briefly about their efforts to promote the acceleration of stem cell treatments and improve the lives of HD patients.

By the end of the symposium, there was an overwhelming feeling of accomplishment and more importantly a renewed sense of hope for the future of HD treatments.

“It was extremely successful and I believe everyone left feeling very optimistic about the future for HD families,” said Saldaña. “There is a light at the end of the tunnel.”

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Patient Advocates Ron Shapiro, Adrienne Shapiro, David Saldana, Frances Saldana, Daniel Medina with Karen Ring from CIRM


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Rare Disease Day, a chance to raise awareness and hope.

logo-rare-disease-day

Battling a deadly disease like cancer or Alzheimer’s is difficult; but battling a rare and deadly disease is doubly so. At least with common diseases there is a lot of research seeking to develop new treatments. With rare diseases there is often very little research, and so there are fewer options for treatment. Even just getting a diagnosis can be hard because most doctors may never have heard about, let alone seen, a case of a disease that only affects a few thousand individuals.

That’s why the last day of February, every year, has been designated Rare Disease Day.  It’s a time to raise awareness amongst the public, researchers, health  professionals and policy makers about the impact these diseases have on the lives of those affected by them. This means not just the individual with the problem, but their family and friends too.

There are nearly 7,000 diseases in the U.S. that are considered rare, meaning they affect fewer than 200,000 people at any given time.

No numbers no money

The reason why so many of these diseases have so few treatment options is obvious. With diseases that affect large numbers of people a new treatment or cure stands to make the company behind it a lot of money. With diseases that affect very small numbers of people the chances of seeing any return on investment are equally small.

Fortunately at CIRM we don’t have to worry about making a profit, all we are concerned with is accelerating stem cell treatments to patients with unmet medical needs. And in the case of people with rare diseases, those needs are almost invariably unmet.

That’s why over the years we have invested heavily in diseases that are often overlooked because they affect relatively small numbers of people. In fact right now we are funding clinical trials in several of these including sickle cell anemia, retinitis pigmentosa and chronic granulomatous disease. We are also funding work in conditions like Huntington’s disease, ALS or Lou Gehrig’s disease, and SCID or “bubble baby” disease.

Focus on the people

As in everything we do our involvement is not just about funding research – important as that is – it’s also about engaging with the people most affected by these diseases, the patient advocate community. Patient advocates help us in several ways:

  • Collaborating with us and other key stakeholders to try and change the way the Food and Drug Administration (FDA) works. Our goal is to create an easier and faster, but no less safe, method of approving the most promising stem cell therapies for clinical trial. With so few available treatments for rare diseases having a smoother route to a clinical trial will benefit these communities.
  • Spreading the word to researchers and companies about CIRM 2.0, our new, faster and more streamlined funding opportunities to help us move the most promising therapies along as fast as possible. The good news is that this means anyone, anywhere can apply for funding. We don’t care how many people are affected by a disease, we only care about the quality of the proposed research project that could help them.
  • Recruiting Patient Advocates to our Clinical Advisory Panels (CAPs), teams that we assign to each project in a clinical trial to help guide and inform the researchers at every stage of their work. This not only gives each project the best possible chance of succeeding but it also helps the team stay focused on the mission, of saving, and changing, people’s lives.
  • Helping us recruit patients for clinical trials. The inability to recruit and retain enough patients to meet a project’s enrollment requirements is one of the biggest reasons many clinical trials fail. This is particularly problematic for rare diseases. By using Patient Advocates to increase our ability to enroll and retain patients we will increase the likelihood a clinical trial is able to succeed.

Organizing to fight back

There are some great organizations supporting and advocating on behalf of families affected by rare diseases, such as the EveryLife Foundation  and the National Organization for Rare Diseases (NORD).  They are working hard to raise awareness about these diseases, to get funding to do research, and to clear away some of the regulatory hurdles researchers face in being able to move the most promising therapies out of the lab and into clinical trials where they can be tested on people.

For the individuals and families affected by conditions like beta thalassemia and muscular dystrophy – potentially fatal genetic disorders – every day is Rare Disease Day. They live with the reality of these problems every single day. That’s why we are committed to working hard every single day, to find a treatment that can help them and their loved ones.

The Critical Role of Patient Advocates in Accelerating Stem Cell Cures

At CIRM, our goal is to bring stem cell therapies to patients with unmet medical needs, and we do that by funding the most promising and innovative research in regenerative medicine. A critical component of this goal is to support our patient advocates and make sure that their voices are heard.

At this year’s World Stem Cell Summit, patient advocates from around the world, representing a breadth of diseases and disorders, came together to share their stories, goals, and needs with the larger scientific community.

One session that particularly stood out, was “Accelerating Cures: The Critical Role of Patient Advocates” on Day 3 of the conference. This panel featured key leaders in patient advocacy:

  • Don Reed, the “Grandfather of Stem Cell Research Advocacy”, Vice President of Public Policy at the Americans for Cures Foundation
  • Frances Saldaña, an advocate for Huntington’s disease (HD) and founder of HD-Care at UC Irvine, which is a support group to advance HD research and clinical care
  • Tory Williams, the Executive Director of the Alabama Institute of Medicine (AIM) which raises funds and awareness for stem cell treatments and cures of disease and injury and the author of “Inevitable Collision

The panel was moderated by our fearless leader and head of communications, Kevin McCormack. Each speaker shared their story about how they became a patient advocate and what they are currently doing to push the pace of stem cell research.

Don Reed, Kevin McCormack, Frances Saldana, Tory Williams.

Don Reed, Kevin McCormack, Frances Saldana, Tory Williams.

Don Reed described the heartbreaking story of his son Roman Reed, who suffered a severe spinal cord injury while playing football. Through Don and Roman’s relentless efforts, “Roman’s Law” was passed in 1999, which raised $17 million in California state funding for spinal cord injury research. Don was also a key instigator for the passage of Proposition 71, which gave $3 billion dollars to our agency to fund stem cell research. He continues to be a passionate advocate for stem cell research and spinal cord injury patients, and recently published a book called “Stem Cell Battles: Proposition 71 and Beyond” which you can read more about in our recent blog.

Next, Frances Saldana told a compelling story of raising a family of three beautiful children with a husband who had Huntington’s disease. Unaware of his condition when they were together, Frances’ world took a devastating turn when he died of HD, leaving her to question whether her children would face the same fate. Sadly, all three of Frances’s kids carried the HD mutation. Having to deal with the passing of her two daughters, and a son who is battling the end stages of this disease, Frances decided to share her experience with others and to create a support organization called HD-Care so that others wouldn’t have to face similar experiences alone. HD-Care is conducting an aggressive campaign to bring visibility to HD and supports cutting-edge research in the field including the work done by CIRM-grantee Dr. Leslie Thompson at UC Irvine.

Frances told the audience that her happiest moment since this all began was when her daughter Margie, already suffering from symptoms of HD, spoke at CIRM in 2007. She saw the Board and the scientists and thought, “somebody cares, and somebody will find a cure.” It was a new chapter for her, she explained, and she knew something good was going to happen.

Lastly, Tory Williams, introduced the Alabama Institute of Medicine, which is a non-profit organization that supports the stem cell community with education and public dialogue. She started the institute following both personal and family experiences with cancer and after TJ Atchinson, a close family friend, suffered a severe spinal cord injury. Along the way, she forged a close relationship with Roman Reed who helped her pass TJ’s law in 2013, which is an Alabama state law that promotes spinal cord injury research.

“The goal [of AIM],” said Williams, “is to make a difference in people’s lives affected by disease and injury by helping to advance medicine to eradicate these debilitating issues.”

Laurel Barchas, Student Society for Stem Cell Research

Laurel Barchas, Student Society for Stem Cell Research

When the session was opened up to questions, the atmosphere in the room turned electric. Patients and scientists stood up to tell their stories and asked hard questions. One question came from Laurel Barchas, one of the founders of the Student Society for Stem Cell Research, who asked how we as a society can advocate for mental illness and similar diseases where the symptoms are not visible and where patients are either embarrassed or hesitant to make their disease public. Another question was how emerging countries like Mexico who don’t have the same benefits and infrastructure as the US can promote and support patient advocacy.

The mood of the advocates was positive but measured. They know that new treatments and cures take time but they also pointed out that many people don’t have much time so we have to work as hard as we can to help them.

The panel ended with the consensus that the voices of patient advocates are invaluable, and that they will be the key to accelerating stem cell therapies into cures. Frances Saldaña urged other patient advocates that the key to progress is to be aggressive, and be unafraid to be out there. Don Reed concluded on a similar note with quote from Shakespeare’s Hamlet:

“Whether ’tis Nobler in the mind to suffer

The Slings and Arrows of outrageous Fortune,

Or to take Arms against a Sea of troubles,

And by opposing end them.”


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CIRM Scholar Spotlight: Berkeley’s Maroof Adil on stem cell transplants for Parkinson’s disease

Maroof Adil, CIRM Scholar

Maroof Adil, CIRM Scholar

Stem cell therapy has a lot of potential for Parkinson’s patients and the scientists that study it. One of our very own CIRM scholars, Maroof Adil, is making it his mission to develop stem cell based therapies to treat brain degenerating diseases like Parkinson’s.

Maroof got his undergraduate degrees from MIT in both Chemical Engineering and Biology, and a PhD in Chemical Engineering from the University of Minnesota. As a graduate student, he dived into the world of cancer research and explored ways of delivering cancer-killing genes specifically to cancer cells in the body while leaving healthy tissues in the body unharmed.

While he enjoyed his time spent on cancer research, he realized his main interest was to apply his skills in chemical engineering and materials science to understand biological problems. This brought him to his current position as a postdoc at UC Berkeley in the Schaffer lab.

Maroof is doing some pretty cutting edge research to develop 3D biomaterials that will vastly improve the transplantation and survival of stem cell derived neurons (nerve cells) in the brain. Check out our exclusive interview with this talented scientist below!


Q: What are you working on and why?

MA: I have always been excited about finding engineering solutions to medically relevant problems. I decided to do a postdoc at UC Berkeley in David Schaffer’s lab because I wanted to combine chemical and materials engineering skills from my graduate research with stem cell technologies to solve biological problems. One of the exciting parts of Dave’s lab, and a reason why I joined, is that he is working on translational stem cell-based regenerative therapies for central nervous system diseases such as Parkinson’s and Huntington’s.

My current research is motivated by the need to find better therapies for these neurodegenerative diseases. While stem cell-based regenerative medicine is an up-and-coming field, there are still a lot of challenges that need to be addressed before stem cells can be successfully used in the clinic. There are three main challenges that are most relevant to my research. First, we need to improve the efficiency of stem cell differentiation, i.e. how well we can convert these stem cells to the mature, functional neurons that we need to treat neurodegenerative diseases. Second, after implanting these cells into the body, we need to increase their survival efficiency. This is because one of the main issues with stem cell-based transplants right now is that after implantation, most of these cells die. Given these first two challenges, we need to generate a lot of cells in order to effectively treat degenerative diseases. The third challenge is to make good quality, functional, transplantable cells in a large-scale fashion.

So given my chemical and materials engineering background, I wanted to see if we could use biologically inspired materials (biomaterials) to address some of these issues with stem cell differentiation and transplantation. In brief, we are developing functionalized biomaterials, differentiating stem cells within these biomaterials into neurons, characterizing the quality of these neurons, and testing the function of these stem cell-derived neurons in animal models of disease.

A major focus of our lab is to develop 3D biomaterials to increase the efficiency of large-scale production of clinical-grade stem cells [and the mature cells that are derived from them]. Our preliminary results suggest that we can get higher numbers of better quality neurons when we differentiate and grow them in 3D biomaterials compared to when they are traditionally grown on a flat, 2D tissue culture surface. Presently, I’m trying to verify that our 3D method works in the lab. If it does, this technology could help us save a lot of time and resources in generating the type of cells we need for effective cell replacement therapies.

Stem cells growing as clusters in 3D[1]Neurons generated in 3D platforms 1[1]

Stem cell derived neurons grown in 3D cultures (left) and generated on 3D biomaterials (right). Images courtesy of Maroof Adil.

Q: Your research sounds fascinating but complicated. How are you doing it?

MA: It’s certainly a multidisciplinary project, and constantly requires us to draw ideas from diverse fields including polymer chemistry, developmental biology and chemical engineering. I am very grateful to be part of a resourceful lab, to my mentors, and to have amazing, motivated people working with me. UC Berkeley provides a highly collaborative work environment. So for some of the follow-up work that further characterizes the quality of these stem cells and their mature cell derivatives, we are collaborating with other labs at UC Berkeley and at UCSF.

Q: Are you interested in applying this work to other brain diseases?

MA: Certainly. Although we are primarily working on generating stem cell-derived dopaminergic neurons, which are the major cell type that die in Parkinson’s patients, I’m also interested in applying similar biomaterials to derive other types of neurons, for instance medium spiny neurons for Huntington’s disease.

The advantage of some of the materials we are working with is their modular nature. That is, we can tune their properties so that they are useful for other applications.

Q: In your opinion what is the future of stem cells in your field? Will they bring cures?

MA: I am very hopeful given what I’m seeing right now in the scientific literature, and in clinical trials for stem cell-based therapies in general. Right now, there are several trials that are testing the benefit and safety of stem cell-based transplants in different diseases. However, right now there are no clinical trials applying stem cell-derived neurons to treat brain diseases. But I think there’s certainly a lot of promise. There are challenges that we need to address in this field, and some of these I outlined earlier. Researchers are working on finding solutions to these problems, and I think that if we find them, the chances of successfully finding cures will be higher.

Q: Tell us about your experience as a CIRM Scholar.

MA: I started as a CIRM scholar in 2014. It was really great to have a source of funding that lined up with what I was interested in, which was doing translational work in regenerative medicine.

I first began working with stem cells when I started my postdoc career, but I didn’t really have a background in this area. So being new to the stem cell field, I felt that CIRM provided the support structure that I needed. And I’m not just referring to funding. CIRM brings scientists with different scientific backgrounds together in one place, where we can learn from one another, and initiate fruitful collaborations. Being a CIRM scholar makes me feel like I’m part of a bigger community, with other scientists conducting very different, but related stem cell research.

Also, I am a big fan of the CIRM blog. I am able to learn about patients and about other researcher’s backgrounds. It helps you realize that patients and researchers are part of the same field. And I like that concept of bringing the field closer: patients towards researchers and researchers towards patients. I think that is useful to boost motivation for researchers, and to give patients a better idea of what we do.

Through CIRM, we’ve had a chance to go out into the local community and present some of our research. For example, the past two years I’ve talked to local high school students during Stem Cell Awareness Week, and that was a really great experience.  I’ve presented to other professionals before, but never to those as young as high school students.  To me, it was quite exciting to realize that these kids are very much interested in the type of work we are doing, and to feel like I was able to influence them to potentially pursue science as a career.

Q: What are your career goals?

MA: I definitely want to stay in science and solve medically relevant problems. It could be nice to be faculty at a research university and in a position to pursue my own independent ideas at the interface of biomaterials and stem cell based therapies. An industry position working towards regenerative medicine or other biologically relevant applications is also an exciting possibility. At this point, being in science is my priority.

Q: What’s your favorite thing about being a scientist?

MA: The excitement you get when your experiments work out, and the joy of making new discoveries. I also like the thrill of designing experiments that may advance the field, and the feeling that what you’re doing day-to-day is contributing to a body of knowledge that others may find useful. I find it especially rewarding to be a scientist in the medical field, working on translational projects closely related to finding cures for diseases.