On Friday, July 19, HOPESters Natty, Preston and Kristen made the trip down to Santa Maria, California to attend the first ever Help4HD International Symposium. The mission of Help4HD International is to facilitate conversations in the research community by providing vital information regarding research and clinical trials to the Huntington’s disease community. For more information on the organization visit: www.help4hd-international.org
Below are the summaries of all the keynote speeches with attached video archives of the presentations:
Congresswoman Lois Capps, Representative, Santa Barbara County^
Congresswoman Lois Capps, the US Representative, Santa Barbara County, made the opening address at the event. She commended the Huntington’s disease community for its resilience in the face of adversity and called for the community to continue to advance on three fronts: supporting caregivers, caring for the sick and bolstering research efforts. Rep. Capps also highlighted the policy advances in assisting Huntington’s disease afflicted individuals and their family such as the HD Parity Act which aims to waive the 24-month waiting period for Medicare eligibility for Huntington’s disease patients. In addition, as a member of the Rare Diseases Caucus, Rep. Capps pledged to push for the study of rare diseases and is positive that the research on rare diseases will produce a ripple effect that will benefit patients of other illnesses like Huntington’s disease.
Dr. Ira Shoulson, Founder HSF (Huntington Study Group) and PSG (Parkinson Study Group)^
Dr. Ira Shoulson, the founder of the Huntington Study Group and Professor of Pharmacology, Neurology and Human Sciences in Georgetown University, was the first keynote speaker at the symposium. Dr. Shoulson focused on the different organizations involved in research, current state of clinical research, and explored the future of Huntington’s disease treatments. He highlights the concern of patients who register for clinical trials, as they are often worried that they might be assigned to receive the placebo treatment; he addresses this concern by emphasizing the documented benefits of the placebo effect. Furthermore, Dr. Shoulson talks about the measures put in place to protect patients undergoing clinical trials, such as informed consent measures and the regulatory processes of the FDA. He then concludes his presentation by discussing the current and future direction that Huntington’s disease research will move in. Dr. Shoulson mentions that current research can be divided into several areas: environmental factors, movement treatment, cognitive-enhancement, and gene expression modification. In the future, he believes that clinical trials may explore treating individuals possessing the dominant Huntington’s disease gene but have yet to develop the symptoms.
Ray Dorsey, MD, MBA, Professor of Neurology and Co-director, Center for Human Experimental Therapeutics ^
Dr. Ray Dorsey, who joined the symposium via a Skype Call, investigates new treatments for movement disorders. Using web-based conferencing, his work seeks to provide care to those with Parkinson’s disease and other diseases, regardless of their geographic location.
Dr. Dorsey began his talk by asking the community to consider what they could do to help the HD community advance research and what clinicians can do to relieve the burden of those affected by the disease.
He stated that the greatest accomplishment in recent medicine was the transformation of HIV/AIDS from a fatal disease to a chronic, manageable one in the past 30 years. Despite a lack of information about retroviruses and the immune system, researchers were able to develop and obtain FDA approval for an effective drug. Now, over the last generation, about ten drugs have been discovered to treat HIV. People can now live healthy, productive lives for decades.
He asks the audience if scientists can do something similar for Huntington’s disease. For example, Nancy Wexler came from a family affected by HD and was able to identify the gene that caused Huntington’s disease. This occurred at a time where genes were thought to cause these diseases, but it was unheard of to determine their location.
Dr. Dorsey then transitioned to how he is advancing the state of Huntington’s disease care through his work with the study, Connect. Huntington. Due to the lack of resources available to individuals in remote or rural regions, telemedicine has become increasingly important as a mechanism to provide these individuals with the care they need. These resources include consultations with neurologists and other doctors on various issues. Individuals should not be denied treatment due to their location.
The aim of the Connect.HD is to provide care to those affected by HD directly in the individual’s home via internet-connected devices like smartphones or computers. There are five states participating in this study, including California. Requirements include the presence of Huntington’s disease in the home as well as access to an internet-connected device. If you are interested in participating in this study, contact Ray Dorsey at firstname.lastname@example.org
Dr. Suzanne Pontow, Co-director, Umbilical Cord Blood Collection Program^
Dr. Suzanne Pontow, Co-Director of the California Umbilical Cord Blood Collection Program at the UC Davis Health System and a Stem Cell Research Program Supervisor at the Institute for Regenerative Cures, discussed both research and clinical applications, specifically for HD patients, for neonatal stem cells and the California Umbilical Cord Blood Public Bank.
She explained that a major research tool for the Institute is the use of neonatal stem cells both in research and clinical applications. The neonatal stem cells are collected from placental tissues and cord blood. The stem cells are made up of mesenchymal and hematopoietic cells, which are multipotent cells. Multipotent cells can differentiate into many but not all types of cells. For instance, hematopoietic stem cells can differentiate into several types of blood cells and mesenchymal cells can differentiate into bone cells, cartilage cells or fat cells, but they are limited to differentiation into these areas. However, both hematopoietic and mesenchymal cells can be induced into a pluripotent state from which they can become any type of cell in the human body.
Dr. Pontow described one example, in which researchers worked with a group of at-risk newborns for autism spectrum disorders. Researchers isolated hematopoietic stem cells from the cord blood of newborns at risk for Huntington’s disease shortly after birth. The cells were cultured, induced into a pluripotent state and were differentiated into neurons. By studying these neurons, they could see if the neurons were developing normally and examine how the neurons responded to various drugs as a way to look for cures or to slow progression of the disease. This “disease in a dish” model is applicable across a wide range of disease types and allows researchers to conduct extensive research about a disease without invasive patient procedures.
Neonatal cell studies are of great importance when it comes to finding treatments for disease. These cells are readily available, easy to harvest and are “youthful”, which according to Dr. Pontow, means that they “last longer in culture and go through more successful divisions than adult derived stem cells.” These advantages allow easier assessment of immune system development and function, making neonatal cells an attractive research and therapeutic tool. With the creation of The California Umbilical Cord Blood Collection Program, there should be more of these cells available for different applications.
Dr. Peg Nopoulos, Professor of Psychiatry, Neurology, UI HD, Kids HD/Kids JHD^
Dr. Peg Nopoulos, Professor of Psychiatry, Neurology and Pediatrics in the University of Iowa, focused her discussion on juvenile Huntington’s disease (JHD). Dr. Nopoulos explained the genetics behind JHD and the differences between the symptoms of adult onset HD and juvenile onset HD. She talked about the Kids-HD program, which is a specialized program where HD experts research on reducing the length of time for diagnosis of potential patients. Dr. Nopoulos explained there are difficulties diagnosing a non-specific symptom because current diagnostic tools cannot distinguish between children with and without the disease due to behavioral cues. Instead, she recommended the use of quantitative MRI as a more accurate tool, which measures the caudate volume of the brain.
Dr. Jan Nolta, Director UC Davis Stem Cell Program, Institute for Regenerative Medicine^
Jan A. Nolta, director of the UC Davis stem cell program and the UC Davis Institute for Regenerative Cures, is moving forward with groundbreaking plans to use mesenchymal stem cells (MSCs) as delivery agents for two potential treatments for Huntington’s disease, BDNF (brain derived neurotrophic factor) and RNA interference. Her research goal is to slow down the striatal (responsible for movement control and communication) degeneration and coax new striatal neurons to be formed in HD patients. Her approach is to use MSC adult stem cells from the bone marrow to repair damaged tissues by responding to the scene of injury and producing healing factors.
A few years ago, she received a grant from the California Institute of Regenerative Medicine to prepare for a clinical trial, where they would implant into the brains of Huntington’s disease victims mesenchymal stem cells that have been engineered to secrete the BDNF needed to protect neurons and keep them healthy. She also has a separate multi-million dollar grant from the state stem cell agency to develop an RNAi delivery system using mesenchymal stem cells. If the trial of MSCs with BDNF is successful, it will provide proof of principle for MSCs as a delivery system for RNAi. “These grants are extremely important to California and to the field of regenerative medicine,” said Nolta. “They enable our teams of scientists and clinicians to plan stem cell clinical trials that will offer treatments to patients who currently have few if any other medical options.”
Patients with HD have much lower levels of BDNF than usual in their brain tissues and mutant protein blocks production of BDNF at RNA level. Nolta’s safe and effective strategy is to use mouse models to produce BDNF from MSC’s transplanted into the striatum as a way to delay progression and potentially recruit new neurons. Her initial data, in conjunction with previous reports, indicate that instriatal BDNF delivery, via MSCs, can prevent motor dysfunction and neuropathological abnormalities in rodent models of HD
Mr. Kevin McCormack, Communications Director, the California Institute for Regenerative Medicine^
Mr. Kevin McCormack, Communications Director of the California Institute for Regenerative Medicine, emphasized the importance of the role of patient advocacy in making a difference for other Huntington’s disease patients and their families. Mr. McCormack explained that he and many others were working to connect patient advocates for Huntington’s disease to form a collective voice to impact policy decisions. He concluded his address by reinforcing the California Institute for Regenerative Medicine’s commitment to improve the lives of patients.
Kayla Horton, Graduate student, CIRM Bridges to Stem Cell Research^
Kayla Horton is from a family both affected by Huntington’s disease and cystic fibrosis. Her familial connections motivated her to study medicine. Horton is studying the use of human fat tissue as a source of stem cells as she is trying to discover the difference between studying adipose cells versus bone marrow in the context of stem cell research.
However, there are some delivery disadvantages. This study is looking for non-invasive delivery of this treatment through intravenous administration. Currently, direct implementation means brain or spinal surgery, which implants the paramedic cells.
Horton is attempting to develop a safe, non-invasive method of delivering hMSCs overexpressing neurotropic factors in order to provide neurodegenerative and protective effects to a CNS injury. Her hypothesis is to use intranasal administration of genetically modified and preconditioned hMSCs that will efficiently migrate to cell injury.
A non-invasive chemotaxic model exploits the MSCs’ innate migratory ability. They move towards the chemicals released by an injury. The goal is to deliver it through the nose, which would be non-invasive and easily repeatable as the MSCs die off.
In a recent study, the team did observe migration of cells in mice from nasal injection to the striatum, which means that Kayla Horton’s research could maybe one day provide a mechanism through which MSCs can be safely delivered to the brain without invasive surgery.
Ms. Teresa Tempkin, RNC, MSN, ANP, UC Davis HDSA Center of Excellence^
Ms. Tempkin’s primary focus is to be a part of the effort to find meaningful treatment for HD and to help families navigate their HD journey. She works with Dr. Jan Nolta and their objective is to obtain FDA approval in order to successfully complete a 2 year phase I trial of cellular therapy in patients with early stage HD. The gene therapy development candidate is donor-derived human MSCs that have been engineered to secrete brain derived neurotrophic factor (MSC/BDNF). Via recruitment from the membership of the Huntington Study Group, her team has enrolled over 325 patients in more than 14 observational studies and clinical trials since 1997. Despite extensive knowledge of the genetics and neuropathology of HD, only palliative treatments exist.
She explained that the study has two phases: Pre-cell and HD-cell. Pre-cell study is a longitudinal observational study to enroll a cohort of early stage HD patients who are potential candidates for planned cellular therapy trial. HD cell phase is the phase 1 clinical trial of MSC/BDNF neurosurgical implanted into striatum using techniques similar to deep brain simulator implantation. In conclusion, she stated that managing expectations and burden of study for participants and caregivers is paramount and that the biggest obstacle in clinical research is time, money and FDA approval.
Dr. Ellen Feigal, Senior Vice President, Research and Development, California Institute for Regenerative Medicine^
Dr. Ellen Feigal, Senior Vice President, Research and Development, California Institute for Regenerative Medicine (CIRM), focused on the CIRM’s experience and future developments. Dr. Feigal explained the research development model used by the CIRM in managing the research projects under its charge. She also highlighted the challenges faced by research organizations in obtaining funding for conducting research.
Lavonne Goodman, MD^
Dr. Goodman began with a question: How do we reach people and get them to see the importance of clinical trials and find the energy to participate when their families are struggling with the disease? There are plenty of families that are passionate about research, but how can they garner that passion to help buoy others into participating?
It’s very hard to find treatment resources that are evidence-based. There isn’t a lot of research that has been done in this respect so the challenge for clinicians is to figure out how to manage Huntington’s disease in a way that is safe and effective.
Goodman facilitated a panel of expert physicians worldwide to figure out best practices for caring for a patient with HD. They discussed drug treatment and approached it pharmalogically, but realized the need to educate family members about the disease and teach them how to promote the health and well being of Huntington’s disease patients. One can print out the documents and take them to one’s physician in order to provide a resource of care.
Goodman studied chorea, obsessive compulsion, behavior issues and is now presently looking at psychosis, apathy, anxiety, agitation and sleep disorder. There is currently no evidence-based treatment for these symptoms. The goal is to give some guidance to patients, families, generalists on how to properly manage these specific symptoms.
For more information on the algorithm and Dr. Goodman’s work, visit http://hddrugworks.org/
Dr. Nathan Goodman, PhD, Systems for HD^
Dr. Nathan Goodman is a senior scientist at The Institute for Systems Biology in Seattle. A PhD computer scientist, he has expertise and extensive history in the building and management of large databases in biologic systems. He, with support from the Hereditary Disease Foundation, is the primary author of HDBase, a web site which assembles datasets of interest to HD researchers, including reported drug studies in HD mouse models. He is in charge of web-based data acquisition and storage. His presentation was on technology-driven research for HD treatments. To find drugs, he stated that we should start at the start and fix the “bad gene”. The second idea is to shut down the “bad gene” via ISIS RNA drugs. The third idea is to find earliest effects via human observation trials or study of HD mice. He talked about methods to find genetic modifies to slow down HD. One method he mentioned is the ISB method, which is a whole genome sequencing of HD families and individuals.
The first ever Help4HD Symposium ended with two powerful advocate stories by Francis Saldaña and Margaret Gallardo.
KP, PL & NJ 2014