The 21 st Century Cures Act and Its Effect on Stem Cell Research and Therapy

Navied_Akhtar
by Navied Akhtar

Navied Akhtar has been accepted as a PhD candidate in the Biomedical Engineering department and is completing an M.S. in biotechnology from UCI. Prior to his scientific training, he completed a B.A. in Political Science from UC Irvine and changed careers into scientific research in 2013. He is currently a member of the Downing Epigenetics Engineering Laboratory and is focused on elucidating the mechanisms involved in cell differentiation and identity.

In modern day medical research, the advent of stem cells has shown immense potential and insight as a means for therapy and information regarding human physiology. Stem cells have been used for crucial therapies such as bone marrow transplants and skin grafts, however their use has not been without question. The ethical dilemmas that arise from the use of stem cells come from philosophical questions of what constitutes a human life and when an embryo can be deemed as a living entity. The answer to these questions guide policy and, ultimately, the amount of funding that is being given to the research of stem cell therapy.

There have been many laws set into place specifically in regards to stem cell research and therapy. Currently, the Dickey-Wicker Amendment, passed in 1995, prohibits the use of NIH funds for creating of human embryos solely for research purposes or for research in which embryos are destroyed. 3 Although this type of research is done elsewhere in the world, the NIH still upholds this ban of funds to this day. States vary in their bans and restrictions on stem cell use. Some states specifically ban human reproductive cloning or ban the use of public money for reproductive cloning, while other states specifically allow therapeutic cloning. 2 These statutes dictate what and how research can be conducted in a given state, and are important for the freedom of what can be researched.

Although there are limitations to how stem cell research and therapies can be deployed, some policymakers feel that stem cells need to be put to use as fast as possible. The REGROW (Reliable and Effective Growth for Regenerative Health Options that Improve Wellness) Act was introduced by Senator Mark Kirk in March of 2016. The REGROW Act aimed to conditionally approve therapeutic products without initiation of large-scale clinical trials. This act would allow phase 3 trials to be circumvented if a particular therapy can show effectiveness in phase 2 trials. 6 The average sample size of phase 2 trials is about 50 while phase 3 trials can grow to as large as 3000 patients. 7 There was an outcry from the scientific community regarding the dangers of the REGROW Act due to concerns that patient safety is being put on hold to allow access to untested medications or treatments. The REGROW Act is still set as “introduced” in the Senate, so no decision has been made as of yet, but there is a new bill that echoes the sentiments of the REGROW Act and poses some of the same concerns: The 21 st Century Cures Act.

The 21 st Century Cures Act is an important piece of legislature that will affect the landscape of scientific research and medicine. The bill aims to accelerate the discovery, development, and delivery of cures to the general public. The bill has been backed by all manner of companies and policy makers, passing in the House of Representatives by 344-77 and in the Senate by 94-5. It allocates 1.75 billion USD for each of the fiscal years 2016 to 2020 for spending by the NIH and Cures Innovation Fund. 500 million of the 1.75 billion dollars will be for the Accelerating Advancement Program, with 35% of the remaining money allocated for early stage investigators, 20% for high-risk, high-reward research, and 10% for intramural research. The Accelerating Advancement Program is the hallmark of the Cures Act, a program that amends Section 506 of the Federal Food, Drug, and Cosmetic Act to allow a surrogate endpoint to approve a therapy for release into a market. In the following five years, the drug manufacturer would have to conduct its own follow up research to ensure the efficacy and safety of the treatment. 1

There is a key amendment in this bill that is crucial to answering the question of whether or not the decision making process of accelerated approval will ensure protection of consumers. This amendment utilizes evidence from clinical experience to “help to support the approval of a new indication for a drug approved under [accelerated approval]” and “to help to support or satisfy post approval study requirements.” The only requirements written in for accelerated approval past a “reasonable likelihood” that there will be clinical benefit, is that one or both of two requirements are met: (1) That the manufacturer conducts studies after accelerated approval to verify the predicted effect on mortality or other clinical benefit and (2) That the manufacturer submits copies of marketing materials for the drug during the preapproval period. 4 The addition of the amendment will allow for what is effectively anecdotal evidence to be used as actual evidence to support the requirement for accelerated approval.

Furthermore, the verbiage surrounding the term “surrogate endpoint” is loose at best. The idea of a surrogate endpoint is to produce a clinically relevant point in which to be able to measure the efficacy and safety of a drug. In the Cures Act, the definition of what constitutes a surrogate endpoint is left rather open-ended. It reads as such: “ The term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product.” 1 It is worrisome to write that this endpoint can be a marker that is not a direct measurement of clinical benefit, but is known to predict clinical benefit. This leaves open a large workaround for accelerated approval of drugs that may have no business being approved.

Envision a scenario in which a stem cell therapy is developed that shows some kind of promise in curing a disease. The Cures Act would allow for a fast track for FDA approval of this therapy to be released to the public for use. This therapy could then be used moving forward to treat this disease, and society is made more robust and effective because of this act. The fact that there are likely to be stem cell therapies that will have been proven safe which can be released to the public more quickly is the main draw of the Cures Act. Lives would be changed for the better, and much more quickly, than without the Cures Act. This is the most ideal case that the act can provide, but what of the other side of the coin?

There are countless stories of why having a phase 3 trial and taking the time to know the outcome of a treatment on a larger sample size of patients is of paramount importance. The story of Tysabri is just one of the many. Tysabri is a monoclonal antibody developed to treat Multiple Sclerosis in an otherwise treatment resistant population. Tysabri’s phase 2 trials were conducted on 213 patients, while the phase 3 trial was conducted on 2113 patients. None of the phase 2 trials produced fatalities linked to the use of Tysabri. In the phase 3 trial however, three patients developed progressive multifocal leukoencephalopathy (PML), inflammation of the white matter of the brain, due to JC virus and ultimately passed away from the symptoms. 8,9 There is no known cure to JC virus, but it is usually cleared by the host’s immune system and is asymptomatic, unless the patient is immunocompromised. Tysabri comes with a strict warning on the box and from medical practitioners that developing PML is a risk, and although the drug is effective in treating Multiple Sclerosis, it is not used as the first line of defense against the disease. The phase 3 trial provided evidence for an estimate of 1 in 1,000 patients developing PML from JC virus. 10

Now, imagine if the Accelerated Approval Program was in full effect before the release of Tysabri. Phase 2 clinical trials showcased Tysabri’s efficacy and safety, and there was more than enough evidence to prove it is “reasonably likely” that this drug works. Tysabri would have been an excellent choice to be fast tracked and approved given the Cures Act verbiage. The aftermath of releasing Tysabri to the market would have been catastrophic since the impact of the JC virus was not known until phase 3 trials. Any individual that was immunocompromised would be at an extremely high risk for activation of JC virus and PML. Even with the knowledge from the phase 3 clinical trials, 517 cases of PML were reported from 130,000 people being treated with the medication in phase 4 studies. 10 How many of the immunocompromised population would develop these symptoms from JC virus without the knowledge from the phase 3 trials? Thankfully, we will never have to know the answer to that question, but it begs the question of who will be held responsible for such catastrophic consequences in the face of an accelerated approval drug? Now how does this scenario change if a stem cell therapy was being utilized?

In regards to stem cells and regenerative medicine, there is no information that directly addresses these types of therapies in the 21 st Century Cures Act. The use of stem cells is already in a highly controversial position and fast tracking experimental therapies that only anecdotally show positive results could be detrimental to the acceptance of stem cell research and therapies in the future. There is evidence of unregulated stem cell therapies leading to development of cancer at the site of treatment. What if in a certain subpopulation, the application of a stem cell therapy would yield a similar result as that of Tysabri? Those who are at odds with the use of stem cells could portray the use of stem cells as therapy as inherently dangerous, and extend it to the thought that it is a waste to even fund it. The Cures Act provides very little gain for the field of stem cells, and the framework provides a lot to lose.

The greatest unknown is that if a therapeutic treatment is fast tracked and turns out to have a dangerous consequence; will the blame be placed on the scientists, legislatures, industry, or the treatment itself? Could we see stem cell therapies be preemptively fast tracked without checking for safety leading to cancers or fatalities in a large population? Would the stigma of stem cell therapy then change because stem cell therapies are seen as dangerous and highly experimental? We approach a slippery slope at this point because there are too many unknowns, but history has shown us that it is neither policy makers nor the pharmaceutical industry that gets the blame in cases such as this. The only way stem cell research and therapy can make it through with this new bill enacted, is that the process for accelerated approval be strict and have the safety of the consumer in mind before all else.

References:

  • H.R.6 – 21 st Century Cures Act. H. Rept. 114-190. The Library of Congress. Retrieved 12/6/16
  • National Institute of Health, Stem Cell Policy. https://stemcells.nih.gov/policy.htm Accessed 12/6/16
  • P.L. 104-99 H.R. 2880. The Library of Congress. Retrieved 12/6/16
  • Title 21-Food and Drugs. Chapter 9-Federal Food, Drug, and Cosmetic Act, Subchapter V-Drugs and Devices, Part A-Drugs and Devices. 21 USC 356 Retrieved 12/6/16
  • Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC). NIH Categorical Spending. Report.nih.gov Published February 10, 2016
  • S. 2689 – REGROW Act. The Library of Congress. Retrieved 12/6/16
  • Ye, Fei. Design and Analysis of Phase III Clinical Trials. Presented on June 19, 2008.
  • O’Connor et al., Relapse rates and enhancing lesions in a phase II trial of natalizumab in multiple sclerosis. Multiple Sclerosis. 2005 Oct; 11(5):568-72
  • Hutchinson, M. Natalizumab: A new treatment for relapsing remitting multiple sclerosis. Therapeutics and Clinical Risk Management. 2007 Jun;3(2): 259-268
  • MS Research Update 2015. Multiple Sclerosis Association of America: Tysabri. Accessed 12/6/16
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The positive impact of negative data

Irena
The positive impact of negative data
by Irina Nesterenko

The heart of scientific research is hypothesis-driven experimentation. Although we phrase the hypothesis as a relationship between variables with a predicted outcome, the rigorously-controlled experiment that follows is actually designed to disprove something — to reject the null hypothesis, which states that there is no such relationship between the tested variables. Positive data supports our hypothesis and rejects the null hypothesis, and best of all, positive results afford us the graphs and pictures that we so desperately need in order to publish, to include as preliminary data in grant applications, and to fuel further investigation.

Negative or non-confirmatory results are scientifically sound outcomes that fail to reject the null hypothesis. Often they are not pursued further or hidden in supplemental figures. At worst, negative results are omitted without acknowledgement or discussion, or even “fudged” to appear as positive data. But I like to think on the bright side… At best, the results that fail to reject the null hypothesis can inspire new avenues of research as they force us to refine or restructure the initial hypothesis.

So, if positive and negative data are two sides of the same coin, both necessary to advance scientific inquiry, then why do we rarely, if ever, see negative results published? Reviewers and readers alike clamor for statistically significant, easily digestible data, causing a publication bias towards the “sexy” results that clearly move the field forward. But the reality is, a great deal of the results we obtain are non-confirmatory and often are relegated to a “file drawer” of unpublished and largely forgotten data.

Many argue that the time and effort invested in writing up negative data is a lost opportunity to write about positive data to publish in conventional journals. However I believe this is the beginning of the slippery slope to confirmation bias. Exploring why negative results are taking place can open new avenues and lead to breakthroughs in the field as we challenge accepted models. It can open new lines of communication between research groups experiencing the same recurring roadblocks. It’s the ethical way to handle the results that disappoint and confound us; transparency helps us all!

Indeed, the idea that transparency allows us to work better and smarter has been touted in science, politics, and journalism. What may seem like an idealist abstraction has very real consequences in medicine: peer-reviewed, published clinical trial data informs how doctors manage the course of their treatments. In cases of confirmation bias, mild side effects may be accidentally omitted in studies where the pressure to validate new therapies is high. To increase transparency in publishing, several journals now publish all documents and communications from the review process, and some journals even make the raw data available to allow for independent peer review outside of the publishing pipeline.

Stringent review and careful oversight in the reporting of negative results will silence the petty complaint that those who publish them are only doing so to pad their resumes with publications. Negative results are simply insufficient without rigorous documentation and reporting of experimental assumptions and parameters, and as such, should be reviewed with the same scrutiny we turn towards our positive results.

This idea gained momentum in the public eye over the last 15 years, bringing the advent of several journals committed to publishing rigorously-reviewed negative or contradictory results (a selection of actively-publishing journals listed below). Professional social media site ResearchGate is an excellent platform to ask questions, share negative data, and forge collaborations worldwide. Working together, using a transparent and rigorous approach, we can illuminate what seems inscrutable and conquer what seems insurmountable when we work alone.

All Results Journals, published by SACSIS*

http://www.arjournals.com

F1000Research, published by same

http://f1000research.com

Journal of Articles in Support of the Null Hypothesis, published by the Reysen Group

http://www.jasnh.com

Journal of Contradicting Results in Science, published by SciBiolMed.Org

http://jcrsci.org

Journal of Negative Results in BioMedicine, published by BioMed Central

http://www.jnrbm.com

Journal of Pharmaceutical Negative Results, published by Wolters Kluwer

http://www.pnrjournal.com

New Negatives in Plant Science, published by Elsevier

http://www.journals.elsevier.com/new-negatives-in-plant-science

PLOS Missing Pieces Collection, published by PLoS

http://collections.plos.org/missing-pieces

Irina Nesterenko is a graduate student researcher and a NINDS T32 fellow in the laboratory of Dr. Olga Razorenova in the Molecular Biology and Biochemistry Department at UCI. Her current research is focused on the role of low-oxygen conditions in the survival of therapeutic stem cells in stroke, towards the development of improved cell-based therapies.

* Author volunteers with the All Results Journals as an English copyeditor.

 

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The interface between immunology and neurobiology: Evaluating the promise of stem cells for treating Multiple Sclerosis

April is National Awareness month for Multiple Sclerosis (MS). To raise awareness, the  Walsh Lab from the Sue & Bill Gross Stem Cell Research Center at UC, Irvine participated in the walk and hosted a lab tour on Saturday, April 11th. Our current fellow, Warren Plaisted, explains what current research is being done regarding MS.  The National Multiple Sclerosis Society, Pacific Coast Chapter works closely with Dr. Craig Walsh, who is our principal  investigator researching MS. 

Multiple sclerosis (MS) is an autoimmune disorder in which a patient’s own white blood cells, particularly T cells, cross the barrier that normally protects the brain and spinal cord and mistakenly attack myelin, the coating that insulates nerve fibers. Loss of myelin disrupts conduction of nerve impulses from the central nervous system (CNS) to the rest of the body, resulting in a variety of symptoms, including muscle weakness and fatigue, vision loss, loss of balance, and emotional and cognitive decline. In contrast to many other neurodegenerative diseases, the majority of patients with MS develop symptoms between the ages of 16 and 45, making it the leading cause of disability in young women and the second leading cause of disability in young men. Today, there are at least 8 FDA-approved immune modulatory therapies for treating MS, but those drugs are only partially effective and do not address the issue of long-term damage to the brain and spinal cord.

Lab tour at the Sue & Bill Gross Stem Cell Research Center at UCI.

Lab tour at the Sue & Bill Gross Stem Cell Research Center at UCI.

On April 11th the National MS Society, Pacific South Coast Chapter hosted a walk to raise awareness on MS.

On April 11th the National MS Society, Pacific South Coast Chapter.

UC Irvine is one of only 15 institutions in the U.S. to house a Collaborative Center for MS Research (as designated by the National Multiple Sclerosis Society). Established in 2011, the over-arching goal of the Multiple Sclerosis Research Center (MSRC) at UCI is to pool talent and resources from laboratories across campus for the development of novel treatment strategies against MS. One such laboratory is that of Dr. Craig M. Walsh, co-director of the MSRC. Located in the Sue & Bill Gross Stem Cell Research Center, Dr. Walsh’s team is using mouse models of MS to investigate how transplanted stem cells can control immune cell infiltration into the CNS and promote myelin regeneration. They are particularly interested in neural precursor cells (NPCs), a type of stem cell that can give rise to the main cell types in the brain and spinal cord. Using a virus-induced mouse model of MS, his group recently demonstrated that NPCs derived from human embryonic stem cells suppress inflammation in the CNS through crosstalk with a subset of suppressor T cells called regulatory T cells (Tregs). Moreover, promotion of Treg activity by human NPCs led to remyelination and improvements in motor skills in transplanted mice. Importantly, sustained benefits in ambulation were not dependent on survival of the stem cell graft. CIRM is currently funding Dr. Walsh’s research through the Translational Research grant (TR3-05603).

One current focus of the Walsh lab is the investigation of the therapeutic potential of NPCs generated from human induced pluripotent stem cells (iPSCs), a type of pluripotent cell that can be made from a patient tissue sample, propagated in a dish, and transformed into a neural precursor cell. Since iPSCs maintain the genetic background of the donor, using human iPSC-derived cells for transplantation may circumvent the need for immunosuppressant drugs that leave patients vulnerable to peripheral infection and re-activation of dormant viruses. Similar to their previous work, Walsh’s group has observed that NPCs generated from iPSCs can promote immune tolerance mechanisms through induction of Tregs, resulting in myelin sparing and regeneration. However, in the case of iPSC-derived cells, dampened immune cell accumulation and increased remyelination were not robust enough to improve the motor skills of transplanted mice. This suggests that not all NPCs are created equal, and the identification of the most therapeutically beneficial stem cells will be important before new treatment strategies move into the clinic.


Warren Plaisted Warren C. Plaisted is a Ph.D. candidate and NIH-sponsored pre-doctoral fellow in the laboratory of Craig M. Walsh, Ph.D. at UCI. He’s funded under the NINDS T32 training grant NS082174. His current research is focused on mechanisms of rejection and repair following transplantation of neural stem cells into a virus-induced mouse model of Multiple Sclerosis. He has additional experience using human pluripotent stem cells to establish in vitro and in vivo disease models in areas where current models do not exist or do not adequately recapitulate patient symptoms.

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Public Speaking Tips for the Evolving Scientists

Faculty members of the Sue and Bill Gross Stem Cell Research Center at UCI, Peter Donovan, Leslie Thompson, and Ping Wang recently launched the Workshop Series for the Evolving Scientist, to provide presentation and public speaking guidance and training for graduate students, postdoctoral scholars, and faculty.Bri McWhorter, the facilitator of the training, has graciously provided us with her quick Public Speaking Tips by using the acronym W.A.V.E which she invented.To learn more about the training make sure to read the recent article in the Ayala Newsletter, Scientists Learn How to Activate to Captivate

 

W.A.V.E.

 

MentorsLine-Up_Dec8th

1. Before you go on stage you want to Warm-up. In order to be physically present and work out your nerves, you must warm-up your body and voice. This is especially important because your body and voice are your key tools in communication.

WarmUp_Dec8th_Training_2014

2. Next you want to make sure your speech has Actions. What are you trying to do to the audience with this information? Are you trying to thrill them? Intrigue them? Bewilder them? People don’t like to be talked at. They like to be talked to. Give them a reason to be involved. If you are going to share exciting research, you need to present it in an exciting way. The facts alone are not enough. You have to bring the information to life.

Reception_Group2

3. Third, in order to keep your audience’s interest you must have Vocal Variety. You achieve this by pausing, altering your pitch, changing your speech pace and varying your volume. Don’t give the audience a chance to tune out.

Fellows_Activity_Dec8th

4. Last, it is important to remember that you are trying to create an Experience for your audience. People recall images so tell your audience a story. Bring them on a journey. Have your presentation come to life. Don’t just make people sit through a boring lecture.

MentorsCircle_Dec8th

No matter what you do during a presentation, try to enjoy yourself. This is an experience for you as well as the audience. It is a much better use of your time if you look forward to sharing your passion for research rather than spend your energy dreading and worrying about an event. I never know exactly how my presentations are going to go. However, as long as I arrive excited to share my message and show others how much I care about communication, I know that I will leave with a sense of pride and accomplishment.

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Stem Cells, you were always on my mind

This blog post was written by Ryan Lim, a current pre-doctoral fellow, who wrote about his recent trip to the Society for Neuroscience meeting in Washington, DC this past November. More than 31,000 people participated at this event, which has been described as, “the largest marketplace of ideas and tools for global neuroscience.”

Logo of the 2014 Society of Neuroscience meeting.

Logo of the 2014 Society of Neuroscience meeting.

I recently had the opportunity to attend the 2014 Society for Neuroscience annual meeting held in Washington D.C. It was a fantastic meeting but, as anyone who has attended knows, the amount of information presented feels like a shotgun blast to the face. There were hundreds of presentations and posters with topics that varied from epigenetics in learning and memory to how a neuroscientist could use the Oculus Rift to test a subject’s responses to a frightening visual and auditory stimulus all while being in a controlled lab environment.One hot topic that was particularly exciting was the focus on adult neurogenesis. Not a new concept but one that has gained a lot of attention in the last decade or so. Emerging data shows several specialized regions in the brain which have active neurogenesis including, most recently, the adult striatum.

Due to the growing interest in adult stem cells scientists have been furiously working to classify stem cell populations in different tissues, as well as determine how they function. At the SFN meeting I was lucky to learn a little more about which cells in the brain function as stem cells and how our brains maintain this precious population. Dr. Fiona Doetsch from Columbia University was one of the presidential speakers who gave a talk entitled “Stem Cells in the Brain: Glial Identity and Niches.” This wonderful lecture highlighted her findings of a glial cell type that resides in the subventricular zone of adult mammalian brains. This is a self renewing cell type that gives rise to progeny that can be classified as different subtypes depending on what stage they are at while on the way to generating a new neuron.

Treatment of mice with ara-C eliminates migrating neuroblasts and precursor cells, essentially eliminating active neurogenesis, but within four days after this treatment you start to see new neurogenesis and only GFAP positive glial remain. Further characterization of these cells show they are GFAP+/BLBP+/GLAST+ astrocytes which become activated, and express EGFR+ & nestin+, by signaling from the surrounding microenvironment. Once these cells become transamplifying cells they lose their GFAP expression on their way to differentiating into neurons. The Doetsch Lab has also shown that these cell types inhabit a special “stem cell niche” that helps maintain the stem cell population. This niche is a unique microenvironment made up of specific cell types, extracellular matrix, and structure that all support the astrocytic stem cells. One example of a novel attribute within this niche is the presence of specialized vascular cells. These cells lack astrocyte endfeet, and pericyte, coverage and directly contact these glial stem cells to provide signals which can help the cells maintain quiescence. Continued research in the Doetsch Lab is focused on defining the signals that tell these stem cells when to proliferate, where to migrate, and how to connect to the existing network of neurons; one possibility being signaling by regional innervation into the niche. Lineage mapping of these neural stem cells and insight into how the brain regulates communication to these cells provides the groundwork so that we may elucidate the functional consequences of adult neurogenesis. Moreover, these findings will help guide understanding of brain repair and the development of CNS pathologies.

It is clear from this lecture that as scientists working on stem cells, we should all try and think of ways in which we can take advantage of these novel adult stem cell populations in our research, and how these cells might be affected during disease. Although these cells have been designated a very important role in the population one cannot ignore those others in the population which provide societal support and allow these individuals to properly function. All individuals and cell types that make up the larger regional population deserve our focus if we are to truly decipher how biological processes occur and diseases develop.

Ryan Lim, MA, CIRM fellow

Ryan Lim, MA, CIRM fellow

Ryan Lim, MA, is a current CIRM predoctoral fellow working in the laboratory of Dr. Leslie Thompson at the Sue & Bill Gross Stem Cell Research Center at the University of California, Irvine (UCI). His current research is focused on using computational biology methods and patient-derived induced pluripotent stem cells to develop cell signatures that define Huntington’s disease. His past experience is in developing novel peptide decorated nanocarriers for targeting and treating breast cancer stem cell. This work was conducted in the laboratory of Dr. Kit Lam at the University of California, Davis (UCD) and lead to his interest in stem cell research.


Citations
1. Ernst, A. et al. Neurogenesis in the striatum of the adult human brain. Cell 156, 1072-1083, doi:10.1016/j.cell.2014.01.044 (2014).
2. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703-716 (1999).
3. Tavazoie, M. et al. A specialized vascular niche for adult neural stem cells. Cell stem cell 3, 279-288, doi:10.1016/j.stem.2008.07.025 (2008).
4. Delgado, A. C. et al. Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction. Neuron 83, 572-585, doi:10.1016/j.neuron.2014.06.015 (2014).

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Rehabilitative Therapy & Stem Cells? What’s the Connection?

Stroke can be a very debilitating condition and patients who have been affected show better results from recovery if they are given access to higher intensity, greater duration rehabilitative therapy. However, our current practices for rehabilitation are limited for many patients due to various reasons such as cost or access. Over in the Cramer lab, we conduct research in stroke rehabilitation and neuroimaging to explore emerging therapies, improve brain repair and reduce disability. Currently the lab is focusing research efforts on trying to make stroke recovery an easier and more cost effective solution.

Virtual reality games provide patients with an enjoyable and fun experiencing and has provided an amazing compliance rate of 97.9% .

Virtual reality games provide patients with an enjoyable and fun experiencing and has provided an amazing compliance rate of 97.9% .

Patients are able to use a computerized gaming system at home to practice their therapy and exercises.

Patients are able to use a computerized gaming system at home to practice their therapy and exercises.

Patients are able to use a computerized gaming system at home to practice their therapy and exercises. Therapists were able to adjust game and exercise settings such as level of difficulty to provide just enough challenge to keep patients motivated and engaged. Just as scientific techniques and technology evolve, our lab evolves and advances as well. In a day and age where people are only a button click away and computers are getting more powerful and more portable, we are striving to adapt this technology to new medical rehabilitation practices to improve arm and hand function. One of our major projects utilized some of the currently available technology, adapting it for use in a telerehabilitation system. Patients were able to use a computerized gaming system, set up in their home, to practice their therapy and exercises. Patients were contacted during their home therapy via videoconference calls to evaluate progress and discuss issues. Therapists were able to adjust game and exercise settings such as level of difficulty to provide just enough challenge to keep patients motivated and engaged.

Turning traditional therapy into virtual reality games familiar to people, such as simon says, duck hunt, black jack and poker, provided patients with an enjoyable and fun experience and provided an amazing compliance rate of 97.9% in our pilot study. Patients also made significant gains in arm and hand function on scales used to test for disability post-stroke. We are now evolving our telerehabilitation studies even further by expanding our original computer system with new games and commercially available USB devices repurposed for therapy. This exciting new multi-site study will allow us to expand our discoveries providing the opportunity to bring telerehabilitation into the homes of patients across the nation. We are currently in the planning stages of this project but enrollment will soon be open across multiple sites across the country.

Now you may be wondering how we fit into a stem cell facility if we are focusing on rehabilitation and not on stem cell research. We believe that in order for stem cell therapy to be effective in people, they need an outlet to retrain what was lost. Finding the best techniques for rehab and seeing significant results in patients without stem cell therapy can only be furthered when stem cell therapy advances and becomes a more commonplace practice. These types of rehabilitation programs can only boost the effectiveness of stem cell therapies and provide maximum impact and the best outcomes for our patients. As science and technology advance we can only imagine how they’ll be adapted to better humankind.

Robert Zhou

Robert Zhou started as an undergraduate at UC Irvine when he joined Dr. Cramer’s lab as a student research associate. He has been working with Dr. Cramer on various projects for two years and is now an administrative and clinical research coordinator. He is working on the new telerehabilitation project and hopes more people will be able to take advantage of this new technology.

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The Art Of Stem Cells: An inner look from the curator herself. . .

This blog post was written by Leslie Davis, the curator of The Art Of Stem Cells. She explains her inspiration to curate an art exhibit that brings together two distinct worlds of art and science. The Orange County Contemporary Art (OCCCA) exhibit is part of a growing SciArt culture where artist and scientist are brought together.

OCCCA is located in the heart of the Downtown Santa Ana Artist Village. The exhibition runs from Sept. 6th to Oct. 10th. A special event will take place on Oct. 4th from 6:00 - 10:00pm.

OCCCA is located in the heart of the Downtown Santa Ana Artist Village. The exhibition runs from Sept. 6th to Oct. 10th. A special event will take place on Oct. 4th from 6:00 – 10:00pm.

I first became interested in using my art for medicine and education after reading the work of a “young Harvard med student” in the book, Mountains Beyond Mountains, by Tracey Kidder. The novel told a story told of how one determined man helped the plight of people in Haiti living with Tuberculosis. He was successful in bringing first world treatment to third world citizens through his worldwide organization, Partners in Health. From this inspiration, I created the “virus” show, World in Collision, in 2005, with conceptual metal and glass sculptures on HIV, TB, Malaria and Breast cancer. I interviewed the researchers and painted 4′ x 5′ portraits of them, banded with images of the viruses. I wanted to bring recognition to these dedicated scientists who give so much of their lives to saving ours and to educate the public about their work.

The rest is history. I remember when Mission Hospital came to OCCCA, in 2007, and asked if we could do some art about their new digital imaging building. The exhibit was called, The Art of Imaging. I wanted to do something for the Veterans that were returning home paralyzed and with TBI. I was looking for researchers that were trying to help them. Junjko Cora, a dermatologist’s, at the Beckman Laser Institute, said she knew of an annual Spinal Cord Conference at UCI and made a call to get me on the list. I went and was befriended by a post doc, Katja Piltti. She found me in the crowd and asked my interest in Stem Cells and I told her about my vision and said, “you have to meet my boss Aileen Anderson.”Aileen and her husband Brian Cummings agreed to meet me for lunch and literally taught me what Stem Cell research was all about. I went home now dedicated to make art for the opening of the Sue and Bill Gross Hall, Regeneration exhibit. The Regeneration show at OCCCA opened the week after the building’s opening reception in May 2010. It was so well received by the community and UCI that I began thinking about how to continue the process of recognizing the scientists and educating the community about their work and perhaps bringing funding to the Stem Cell Research Center.

Peter Donovan, previous Director of SCRC, asked me at the first “Center Friend Raiser” if I could help him with a future art show and I said yes. This is if he agreed to let me bring some artists to the Labs to meet directly with the researchers and collaborate in ways to make conceptual art about their work. He said yes and the result has been the Art Of Stem Cells event. It opened to a crowd of over 2,000 with great critical art reviews noting the uniqueness and validity of a show that blurred the lines between art and science, researcher and artist. I received Colliding Worlds by Arthur Miller, from one of my virus researchers, while I was installing the show. He speaks of a new movement that merges Technology, Science and Art, in which he believes will be our new culture. I have to whole heartedly agree with him! I hope you will tell your friends and neighbors to come to the OCT 4th event where you can meet with the artists and researchers themselves. Next week will be the final week of the exhibit which will end on October 10th.

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Leslie Davis was born and raised in California. She attended the Pilchuck School of Glass, Stanwood and Pratt Fine Art Center in Seattle Washington and Santa Ana College. Her passion is using glass as a medium to explore the interaction between light and movement. By 2010 she had met UCI stem cell researchers Aileen Anderson, Brian Cummings, and Peter Donovan. A new passion for Stem Cell Research was born. The Art Of Stem Cells will be the OCCCA’s 4th showing of conceptual medical art.

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