Avoiding the hippocampus during whole-brain radiotherapy prevents cognitive side effects (Adonica Shaw)

Whole-brain radiotherapy can be delivered more safely to patients with brain metastases by avoiding the hippocampus according to a new phase III trial.

At the beginning of the study, scientists hypothesized that radiation to the hippocampal stem cells played a role in cognitive decline. 500 patients were randomized to whole brain radiotherapy, some with and without hippocampal avoidance. The results of the clinical trial found a 26% relative reduction in risk of cognitive toxicity following whole brain radiation therapy with hippocampal avoidance versus whole brain radiotherapy. The cognitive function benefit of hippocampal avoidance did not differ by age.

“This study demonstrates that we can deliver whole brain radiotherapy with similar cognitive outcomes as radiosurgery,” said lead author and co-principal investigator of the phase III trial Vinai Gondi, MD, director of research at the Northwestern Medicine Chicago Proton Center and co-director of the Brain Tumor Center at Northwestern Medicine Cancer Center Warrenville. “These trial results revolutionize our understanding of the cognitive effects of brain irradiation in a manner that has far-reaching implications in terms of the safer radiotherapy treatment of primary or metastatic brain tumors.”

Brain metastases, cancer cells that have spread to the brain from primary tumors in other organs, is one of the most common cancer conditions managed by radiation oncologists. Due to concerns about cognitive decline, whole brain radiotherapy is currently often the last resort, even though it is one of the most effective treatments for brain metastases.

By establishing that the hippocampal region is sensitive to radiation, treatment plans for brain metastases or other brain tumors can employ advanced techniques such as intensity-modulated radiation therapy (IMRT) or proton therapy to reduce dose to the hippocampus and offer brain therapy with less toxicity.

Better model to help speed up new drugs for schizophrenia (Kevin McCormack)

One of the problems in developing new treatments for diseases is finding a model that accurately reflects how a new treatment might work in people. Typically, we’ll test some new approach on a mouse model of a disease, to see if it is safe and works. But often what works in a mouse doesn’t work in people. Now a new study in the journal Nature Communications may have found a better model to test drugs for people with schizophrenia.

Right now, all antipsychotic drugs approved by the Food and Drug Administration (FDA) for schizophrenia target one specific dopamine receptor in the brain. Dopamine is a chemical that acts as a messenger in the brain and it’s thought that imbalances in this receptor are a leading cause of schizophrenia. However, around two-thirds of people with the condition don’t respond to the medications that target this receptor.

So, researchers at the Icahn School of Medicine at Mount Sinai, Eli Lilly and Company, and Sema4 thought that maybe a better way to test potential new medications would be on cells that came from people who actually have schizophrenia, rather than a mouse.

They took cells from 12 people with schizophrenia and 12 healthy people, and turned those cells into neural progenitor cells, the kind of brain cell affected by the disease. They then tested those cells against 135 different medications and found that the patient-derived cells provided lots more information about how those cells would affect someone with schizophrenia than traditional testing methods.

In a news release Adam Margolin, from the Icahn Institute, said these findings could have wider implications:

“This study nicely illustrates the importance of using an integrative genomics approach for improving drug discovery and, ultimately, patient care. The results should be immediately applicable not only to drug discovery for schizophrenia but also more broadly to a wide range of diseases for which more biologically relevant screening models are long overdue.

Visual impairment and vision loss can have a profound impact on a person’s ability to live their life and complete their daily routine. According to the report for the 2016 National Health Interview Survey, 25.5 million Adult Americans 18 and older reported experiencing vision loss. Of these 25.5 million American adults, 15.3 million women and 10.1 million men report experiencing significant vision loss.

While some vision loss has been curbed with contact lenses, antibiotics or even surgery, other more serious conditions like macular degeneration, diabetic retinopathy, and inherited retinal degenerations, present greater challenges.

So what options are available?

Stem cell-based therapy.

Some say emerging stem cell technologies could hold the promise of autologous grafts to stabilize vision loss through cellular replacement or paracrine rescue effects. It is believed that since most of the diseases that lead to loss of vision do so as a result of abnormal vasculature and/or neuronal degeneration, the use of stem cells to stabilize or prevent visual loss may hold great promise. Our stem cell team will discuss these treatments, and what, if any approach may significantly address vision loss for stem cell researchers.

This event will feature Rosie Barrero, a patient advocate and clinical trial participant, Dennis Clegg,Co-Director, UCSB Center for Stem Cell Biology and Engineering and Henry Klassen, MD Ph.D, Director, UC Irvine Stem Cell & Retinal Regenerative Program.

Our Facebook Live event, “Ask the Stem Cell Team About Sickle Cell Disease” is– Thursday, November 1st – from noon till 1pm PST. You can join us by logging on to our Facebook.

Also, make sure to “like” our FaceBook page before the event to receive a notification when we’ve gone live for this and future events.

We want to answer your most pressing questions, so please email them directly to us beforehand at info@cirm.ca.gov.

A recording of the session will be available in our FaceBook videos page shortly after the broadcast ends.

We hope to see you there.

Almost 15 years ago, California voters via approval of Proposition 71 authorized $3 billion to create the California Institute for Regenerative Medicine (CIRM). CIRM, otherwise known as California’s Stem Cell Agency, accelerates stem cell treatments for patients with unmet medical needs.

Credit: Starworks Network

Along with the fact that CIRM has pioneered the way for cutting edge science, we are also global innovators in empowering patient advocates to fully partner in biomedical research funding through a healthcare practice called “Coproduction” that is also being applied to biomedical research processes.

For those of you who are unfamiliar with the terminology, “coproduction” in healthcare in the US has also been called “patient-centered” care or “patient-centered medical home.”  As it is being applied to biomedical research, it is an approach in which researchers, practitioners and the public work together, sharing power and responsibility from the start to the end of the project, including the generation of knowledge. The global movement towards co-production gives patients and patient advocates formal roles as full partners so that research brings about outcomes that improve patients’ health more effectively and efficiently.  Both in healthcare and biomedical research, chronic and life threatening diseases and conditions offer the greatest need and produce the greatest benefits from robust coproduction.

Just last week one of our Board members, Jeff Sheehy, wrote a commentary which appeared in Nature, about coproduction. We spoke to him for a Q&A profile on the piece to give us his thoughts on this emerging trend.

Jeff Sheehy is a former San Francisco City and County Supervisor and a long-time HIV/AIDS activist and pioneer for LGBT equality who has dedicated his life to public and community service. He has served on CIRM’s Board since its inception in 2004.

AS: I know CIRM is unique, but what is one of the things that you see that CIRM does  or has done that’s unlike any other agency.

JS: One of the amazing things about the structure of CIRM is the way in which Proposition 71 actually gives formal power to patient advocates. CIRM is unique because patient advocate members of the Board are full participants in the Grants Working Group, CIRM’s peer review body, including writing reviews for late stage projects. That is one example, but when you look at CIRM, at every level patient advocates are critical to the functioning of the agency.  Advocates exert leadership in reviewing applications and approving funding them, participating in Clinical Advisory Panels to advise and monitor late stage projects, setting budgets, creating strategy, determining policies and selecting leadership of the institution. I believe this is unique – that CIRM treats patient advocates as full partners in the agency’s processes and ensures that participation with formal, statutory power.

AS: What’s one piece of advice that you would pass along to a patient advocate, or those who haven’t yet realized how much power they have to push things forward for certain disease indications?

JS: I would suggest that patient advocacy is beneficial in a number of ways. One is from a purely personal point of view. When one or one’s loved one is diagnosed with a chronic or life-threatening disease or condition, it is terrifying and the sense that one’s future is outside of one’s control is overwhelming.  For instance, when I was diagnosed with HIV in early 1997, even though life-saving combination therapy was just coming onto the scene, I did not have health insurance, did not know how to access care, and was not even completely sold on the efficacy of the new therapy.  I felt that I, like everyone diagnosed with HIV up to that point, had been given a death sentence. Joining my brothers and sisters in ACT-UP not only helped me understand and learn about HIV and the new therapy along with how to access care and the medications, but it also empowered and emboldened me to fight back not only for myself but for everyone impacted by HIV/AIDS. So, I took that first step of becoming an advocate for myself and my community.  Taking action, actively fighting for yourself, your loved ones, your community, learning about your disease and how to combat it—I think this has a psychological and I would argue even a physical benefit because you’re no longer passively accepting the cards you or your loved ones have been dealt.  In HIV, one of the most heavily stigmatized diseases, owning your diagnosis, working with others who have HIV, partnering with one’s caregivers, obliterates psychological barriers imposed by stigma and helps one achieve the self efficacy and resiliency necessary to survive and thrive.

Another way that patient advocates can bring great value to the struggle against chronic and life threatening diseases and conditions is to actively engage in the research process, to become a partner in the search for therapies and cures.  Multiple paths are available.  One can participate in a clinical trial, though it is extremely important to be aware of the risks and to recognize that the benefits of the research are unlikely to be realized by you.  In the first trial of a therapy for HIV in the early 1980s, every participant died, yet almost 15 years later we had developed combination therapy that, as an example of a “Lazarus effect,” literally brought AIDS patients out of their deathbeds. Research/medicine is able to make huge leaps forward due to the altruism of motivated trial participants.

Additionally, you can advocate for funding for research, which should also be linked to advocacy for policy changes that ensure access for everyone to new therapies and cures.  Proposition 71 was led by patient advocates, and CIRM, in its intellectual property policies, mandates access to newly discovered therapies and cures.  Also, if you look at the way CIRM operates, patient advocates take partnering to another level by active and equal participation in the functions of the agency.  Patient advocates not only need to be available to take part, but also we must strongly press the model of coproduction across the board so that other research entities recognize the immense value and benefit of engaging and creating partnerships with patients and patient advocates.