Researchers at the University of California, San Diego School of Medicine have launched a Phase III clinical trial to evaluate the drug isradipine, a calcium channel blocker often used to treat high blood pressure, as a potential new treatment for Parkinson disease (PD). The goal of the study is to determine whether the drug can slow the progression of the disease by keeping the brain’s dopamine-producing cells healthier for a longer period of time.
“Isradipine has been demonstrated to be safe and tolerable in patients with Parkinson’s disease,” said Irene Litvan, MD, site investigator and director of the Movement Disorder Center at UC San Diego Health System. “This new study will determine whether the drug can be effective in slowing the progression of the disease and could, thereby, complement existing symptomatic treatments to improve the quality of life of individuals with the disease.”
PD is a progressive neurological disorder that affects an individual’s speed and amplitude of movements and decreases the speech volume. Patients with PD experience stiffness or rigidity of the arms and legs and walking difficulties in addition to tremors in their hands, arms, legs or jaw. Patients with PD also experience vivid dreams, depression, and constipation.
Isradipine is a Food and Drug Administration-approved drug to treat high blood pressure. Prior population studies have shown that people taking isradipine for high blood pressure have a lower incidence of PD. Additionally, isradipine is in a category of drugs called calcium channel blockers, meaning they inhibit certain cellular functions. Overactive calcium channels may play a role in the death of the dopamine producing cells in the brain that is one of the hallmarks of PD.
A Phase II evaluation of isradipine, which was conducted to determine the safety and appropriate dosage for the drug, was completed in 2012. The study was funded by a $2.1 million grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF), which also supported preclinical research into the effects of isradipine on Parkinson’s progression by D. James Surmeier, PhD, of Northwestern University.
The study, called STEADY-PD, is sponsored by the Parkinson Study Group and is co-lead by the University of Rochester Medical Center (URMC) and Northwestern University. UC San Diego Health System is one of the national research participants.
Patients who are eligible for the clinical trial will have been diagnosed with PD for less than 3 years and are not currently on any dopaminergic therapy such as levodopa, dopamine agonist, or MAO-B inhibitors.
“If it proves to be effective, this drug will change the way we treat Parkinson’s disease, and the major advantage of it is that isradipine is already widely available, inexpensive and will allow for rapid translation of our research into clinical practice,” said Tanya Simuni, MD, principal investigator of the study and professor of neurology at Northwestern University Feinberg School of Medicine. “Although we now have very effective symptomatic treatments to manage Parkinson’s, the development of a disease-modifying intervention remains the Holy Grail.”
Patients with PD are advised not to take this medication if they are not part of this therapeutic clinical trial.
For additional information about this clinical trial, please contact the UC San Diego Health System site coordinator at 858-822-5751 or firstname.lastname@example.org
Protein regulates neuronal communication by self-association
The protein alpha-synuclein is a well-known player in Parkinson’s disease and other related neurological conditions, such as dementia with Lewy bodies. Its normal functions, however, have long remained unknown. An enticing mystery, say researchers, who contend that understanding the normal is critical in resolving the abnormal.
Alpha-synuclein typically resides at presynaptic terminals – the communication hubs of neurons where neurotransmitters are released to other neurons. In previous studies, Subhojit Roy, MD, PhD, and colleagues at the University of California, San Diego School of Medicine had reported that alpha-synuclein diminishes neurotransmitter release, suppressing communication among neurons. The findings suggested that alpha-synuclein might be a kind of singular brake, helping to prevent unrestricted firing by neurons. Precisely how, though, was a mystery.
Then Harvard University researchers reported in a recent study that alpha-synuclein self-assembles multiple copies of itself inside neurons, upending an earlier notion that the protein worked alone. And in a new paper, published this month in Current Biology, Roy, a cell biologist and neuropathologist in the departments of Pathology and Neurosciences, and co-authors put two and two together, explaining how these aggregates of alpha-synuclein, known as multimers, might actually function normally inside neurons.
First, they confirmed that alpha-synuclein multimers do in fact congregate at synapses, where they help cluster synaptic vesicles and restrict their mobility. Synaptic vesicles are essentially tiny packages created by neurons and filled with neurotransmitters to be released. By clustering these vesicles at the synapse, alpha-synuclein fundamentally restricts neurotransmission. The effect is not unlike a traffic light – slowing traffic down by bunching cars at street corners to regulate the overall flow.
“In normal doses, alpha-synuclein is not a mechanism to impair communication, but rather to manage it. However it’s quite possible that in disease, abnormal elevations of alpha-synuclein levels lead to a heightened suppression of neurotransmission and synaptic toxicity,” said Roy.
“Though this is obviously not the only event contributing to overall disease neuropathology, it might be one of the very first triggers, nudging the synapse to a point of no return. As such, it may be a neuronal event of critical therapeutic relevance.”
Indeed, Roy noted that alpha-synuclein has become a major target for potential drug therapies attempting to reduce or modify its levels and activity.
“We will be looking to pinpoint the genes, proteins, chemical pathways and networks involved in these diseases at the single cell level,” said Gary S. Firestein, MD, professor, dean and associate vice chancellor of translational medicine. “This approach allows us to make comparisons across many diseases, revealing new insights and aspects of the disease process. We hope to better understand why some RA patients, for example, respond to therapy and others do not – and develop new therapies that target their condition based upon their particular genetic and environmental variables.”
The effort is part of a five-year, $230 million program called Accelerating Medicines Partnership (AMP), a collaboration between the Food and Drug Administration, the National Institutes of Health (NIH), 10 biopharmaceutical companies and several non-profit organizations. It will initially focus upon autoimmune disorders, type 2 diabetes and Alzheimer’s disease, with other diseases and conditions added in the future. The program for RA and lupus is managed through the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
The unusual cross-sector partnership will emphasize finding tell-tale “biomarkers” for these disease areas, which are molecules that can be helpful for diagnosis or selecting treatment. The group also will identify promising drug targets and ways to reduce the time and cost of developing new therapeutics. A critical component of the effort, say officials, is that industry partners, such as Merck and Pfizer, will make AMP data and analyses publicly accessible to the broad biomedical community.
“To date, treatments for RA and lupus have been aimed at decreasing inflammation and pain,” said Stephen I. Katz, MD, PhD, director of NIAMS. “For the first time, we are bringing together multidisciplinary research teams to achieve a broad, systems-level understanding of these diseases, setting the stage for the development of more effective diagnostic and treatment approaches.”
In a consortium with the University of Colorado, the University of Nebraska and Cedars Sinai Medical Center, UC San Diego will be responsible for using the latest genomics and epigenomics research tools to collect and process tissue and blood samples from patients with RA.
RA is primarily an inflammatory disease of the joints, affecting an estimated 1.5 million Americans, or almost 1 percent of the U.S. adult population. While it most often diagnosed in middle age and occurs with increased frequency in older people, it also strikes children and young adults. Symptoms include pain, selling, stiffness and loss of function in joints. RA typically becomes chronic. There are many treatments, but no cure. Research at UC San Diego in RA has contributed to the discovery of several novel therapies that are currently being used. Despite these advances, many patients still have pain and diminished quality of life.
Both RA and lupus belong to a larger group of autoimmune disorders that includes multiple sclerosis, Crohn’s disease, ulcerative colitis, type 1 diabetes and psoriasis. These diseases, say researchers, share common flaws in immune function and regulation, leading to inflammation that destroys tissues and results in reduced quality of life, disability and increased risk of death.
If successful, the researchers said the combined efforts of academia, the NIH and biotechnology companies can change the way research is performed and create multi-disciplinary teams that can be more effective than individual groups.
101 UC San Diego Physicians in 40 Specialties Named Best Doctors in Region
More than 100 physicians from UC San Diego Health System were named “Top Docs” in the annual San Diego Magazine “Physicians of Exceptional Excellence” annual survey. These physicians represent 40 diverse specialties, from internal medicine and oncology to obstetrics, cardiovascular and surgical care.
“As the only academic hospital in the region, UC San Diego Health System strives to serve the community with the best experts and state-of-the-art health care. We are honored to be recognized in a wide array of medical and surgical specialties,” said Paul Viviano, CEO, UC San Diego Health System. “This designation reflects the dedication of leaders in both clinical practice and research who provide a combination of high quality care, compassion and breakthrough discoveries. The ‘Top Docs’ list is also a valuable tool for patients who may be seeking prenatal care, a specialist for a chronic condition or who may need to select a primary care physician.”
The “Top Docs” annual survey, made possible through a partnership with the San Diego County Medical Society and San Diego Magazine, gives physician peers the opportunity to vote for board-certified physicians practicing in San Diego County to whom they would refer their own patients and family members. This year, there were 778 “Top Docs” named in the region.
Becker’s Hospital Review Names SCVC among “100 Hospitals with Great Heart Programs”
UC San Diego Sulpizio Cardiovascular Center (SCVC) has been named among “100 Hospitals with Great Heart Programs” by Becker’s Hospital Review, a business and legal news publication for hospital and health system leadership.
According to Becker’s editorial team, the hospitals chosen for this list lead the nation in cardiovascular and thoracic healthcare, have pioneered groundbreaking procedures and have received top recognition for the highest quality of patient care.
“Since the doors opened in 2011, SCVC has become nationally recognized for the comprehensive and extraordinary care provided to patients. The facility combines all heart and vascular-related programs, research and technology under one roof,” said Paul Viviano, CEO, UC San Diego Health System. “It is an honor for the cardiovascular team to be recognized for its tireless dedication to superb clinical care and delivery of life-saving therapies every day.”
Researchers at the University of California, San Diego School of Medicine have launched a phase 1 human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with chronic lymphocytic leukemia (CLL), the most common form of blood cancer in adults.
The new antibody targets ROR1, a protein used by embryonic cells during early development and exploited by cancer cells to promote tumor growth and metastasis, the latter responsible for 90 percent of all cancer-related deaths.
Because ROR1 is not expressed by normal adult cells, scientists believe it is a biomarker of cancer cells in general and cancer stem cells in particular. Because it appears to drive tumor growth and disease spread, they believe it also presents an excellent target for anti-cancer therapy.
Developed at UC San Diego Moores Cancer Center by Thomas Kipps, MD, PhD, who holds the Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues, the antibody is called cirmtuzumab (also known as UC-961). In previous animal studies, Kipps’ team reported that ROR1 is singularly expressed on CLL and also on a variety of different cancers, including cancers of the breast, pancreas, colon, lung and ovary. In mouse models of CLL, ROR1 acts as an accelerant when combined with another oncogene to produce a faster-growing, more aggressive cancer.
Cirmtuzumab was developed under the auspices of the California Institute for Regenerative Medicine’s HALT leukemia grant awarded to Dennis Carson, MD, principal investigator, and Catriona Jamieson, MD, PhD, co-principal investigator to develop six distinct therapies against cancer stem cells. Kipps led one of the six projects and generated antibodies against ROR1, leading to the cirmtuzumab trial in patients with CLL.
“The primary goal of this phase I clinical trial is to evaluate whether cirmtuzumab is a safe and well-tolerated cancer stem cell-targeted agent in patients with CLL,” said Jamieson, chief of the Division of Regenerative Medicine, associate professor of medicine, director of stem cell research at UC San Diego Moores Cancer Center, deputy director of the Sanford Stem Cell Clinical Center and a principal investigator of the cirmtuzumab clinical trial.
Michael Choi, MD, assistant clinical professor of medicine and co-principal investigator of the clinical trial said, “The trial will involve patients with relapsed or refractory CLL, who will receive an intravenous infusion every 14 days at Moores, followed by regular monitoring and clinic visits to assess efficacy and identify and manage any adverse effects. Initial treatment is planned for two months.”
To learn more about eligibility for this clinical trial, call Reilly L. Kidwell at 858-534-4801 or Samuel Zhang at 858-534-8127.
Cell surface sugars can promote or inhibit cancer depending upon stage
During cancer development, tumor cells decorate their surfaces with sugar compounds called glycans that are different from those found on normal, healthy cells. In the Sept. 15 online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), researchers at the University of California, San Diego School of Medicine report that sialic acids at the tips of these cancer cell glycans are capable of engaging with immune system cells and changing the latter’s response to the tumor – for good and bad.
“These cell surface glycans can promote or inhibit cancer progression, depending upon the stage of the disease,” said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine. “Our findings underscore the complexity of cancer and the consequent challenges in conquering it. The immune system may be a double-edged sword in cancer, tumor-promoting or tumor-inhibiting, depending upon circumstances.”
Specifically, the researchers found that receptors called siglecs on subsets of neutrophils and macrophages (two types of immune cell) can bind to sialic acids on the surface of tumor cells. Depending upon the stage of cancer and the tumor model used, the scientists reported that interaction between immune cell siglecs and tumor cell sialic acids produced opposite outcomes.
“During initial stages of growth, cancer cells appear to protect themselves from extermination by neutrophils by engaging siglecs via sialic acid-capped glycans,” said Varki, who is also a faculty member of the UC San Diego Moores Cancer Center. “But once the tumor was established, further growth was inhibited by engagement of siglecs on macrophages.”
The findings follow upon research by Varki and colleagues published earlier this year in PNAS that showed anti-tumor antibodies also behave contrarily. Low concentrations of antibodies can support cancer growth, but higher concentrations may inhibit it.
“The fact that the immune system can exert a promoting or inhibiting effect on cancer progression, depending on the situation and stage of disease, has importance for designing clinical trials with drugs that target the immune system,” said first author Heinz Läubli, MD, PhD.
For example, siglecs might prove viable drug targets for preventing early cancer progression. Study co-author Ann Schwartz, PhD, MPH, of the Karmanos Cancer Institute at Wayne State University School of Medicine in Detroit investigated 332 patients with lung cancer to assess whether they had a natural siglec variant that reduced binding to tumor cell surface sialic acids. Such patients have a greater chance for survival after two years, but the effect diminishes and disappears later.
“We need more studies to understand the mechanisms in siglecs mediating the switch between tumor-promoting and tumor-inhibiting before possible therapies can be developed,” Varki said.
Napoleone Ferrara, MD, Distinguished Professor of Pathology and Distinguished Adjunct Professor of Ophthalmology at the University of California, San Diego School of Medicine and senior deputy director for basic sciences at UC San Diego Moores Cancer Center, was named today as one of seven recipients of the António Champalimaud Vision Award in Lisbon, Portugal.
Developed at UC San Diego, effort seeks to identify at-risk toddlers by first birthday
Autism spectrum disorder (ASD) is now estimated to impact one in every 68 children born in the United States. Yet despite its rising prevalence and the known benefits of early detection and treatment, toddlers in much of the United States are routinely not identified as possibly having ASD until well after their third birthday.
“By that time, much precious brain development has already occurred,” said Karen Pierce, PhD, associate professor of neurosciences at the University of California, San Diego School of Medicine and assistant director of the UC San Diego Autism Center of Excellence.
A new 5-year, $5.1 million grant from the National Institute of Mental Health (NIMH) seeks to remedy that by expanding a program developed by Pierce and colleagues to reduce the mean age of ASD diagnosis in multiple cities across the U.S.
The program, called Get SET Early, is based upon a one-year well-baby check that Pierce first described in a paper published in 2011. In those findings, Pierce and colleagues reported that San Diego toddlers who were systematically assessed for ASD around their first birthday typically began receiving treatment within a few months, years before children in many other cities.
With NIMH funding, the Get SET Early program expands upon Pierce’s original model, adding new features and technologies, such as an iPad-based automatic referral system.
The improved model consists of three stages: In the Screening stage, a network of pediatricians conduct repeat evaluations of toddlers at multiple ages – 12, 18 and 24 months – using standardized testing and scoring. “Since the symptoms of autism can come on slowly between 12 and 24 months, if we screen three times we are almost guaranteed to detect the overwhelming majority of children with this disorder,” Pierce said.
In the second Evaluation stage, toddlers who may have ASD are immediately referred to local clinics that specialize in ASD for more detailed evaluation.
In the final stage, Treatment, toddlers showing clear signs of ASD are referred to an established network of healthcare specialists for rapid treatment. “There is evidence that early therapy can have a positive impact on the developing brain,” Pierce said. “The opportunity to diagnose and thus begin treatment for autism around a child’s first birthday has enormous potential to change outcomes for children affected with the disorder.”
The Get SET Early program will expand first to Phoenix, which has one of the oldest average ages of ASD detection in the country. A recent survey conducted by the U.S. Centers for Disease Control found that children with autism living in Phoenix were typically not identified until they were almost five years old.
In her 2011 study, published in the Journal of Pediatrics, Pierce and colleagues created a network of 137 pediatricians in the San Diego region and asked them to include a brief assessment at the toddlers’ traditional one-year health checkup. The assessment consisted of parents or caregivers answering a questionnaire called the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist that queried about a child’s use of eye contact, sounds, words, gestures, object recognition and other forms of age-appropriate communication. Any infant who failed the screening was referred to the UC San Diego Autism Center of Excellence for further testing and re-evaluation every six months until age three.
While the NIMH grant will initially test the feasibility of establishing the Get SET Early model in Phoenix, research and testing will also continue in San Diego to assess the efficacy of new improvements, such as repeat triple screenings and Internet-based tracking of referrals and treatment.
“By creating a simple screening, evaluation and treatment initiation and tracking model, we hope to establish national standards so that one day ASD detection and treatment between the first and second birthday will happen for all children,” said Pierce.
UC San Diego is initial site for first-in-human testing of implanted cell therapy
Researchers at the University of California, San Diego School of Medicine, in partnership with ViaCyte, Inc., a San Diego-based biotechnology firm specializing in regenerative medicine, have launched the first-ever human Phase I/II clinical trial of a stem cell-derived therapy for patients with Type 1 diabetes.
The trial will assess the safety and efficacy of a new investigational drug called VC-01, which was recently approved for testing by the U.S. Food and Drug Administration. The 2-year trial will involve four to six testing sites, the first being at UC San Diego, and will recruit approximately 40 study participants.
“The goal, first and foremost, of this unprecedented human trial is to evaluate the safety, tolerability and efficacy of various doses of VC-01 among patients with type 1 diabetes mellitus,” said principal investigator Robert R. Henry, MD, professor of medicine in the Division of Endocrinology and Metabolism at UC San Diego and chief of the Section of Endocrinology, Metabolism & Diabetes at the Veterans Affairs San Diego Healthcare System. “We will be implanting specially encapsulated stem cell-derived cells under the skin of patients where it’s believed they will mature into pancreatic beta cells able to produce a continuous supply of needed insulin. Previous tests in animals showed promising results. We now need to determine that this approach is safe in people.”
Development and testing of VC-01 is funded, in part, by the California Institute for Regenerative Medicine, the state’s stem cell agency, the UC San Diego Sanford Stem Cell Clinical Center and JDRF, the leading research and advocacy organization funding type 1 diabetes research.
Type 1 diabetes mellitus is a life-threatening chronic condition in which the pancreas produces little or no insulin, a hormone needed to allow glucose to enter cells to produce energy. It is typically diagnosed during childhood or adolescence, though it can also begin in adults. Though far less common than Type 2 diabetes, which occurs when the body becomes resistant to insulin, Type 1 may affect up to 3 million Americans, according to the JDRF. Among Americans age 20 and younger, prevalence rose 23 percent between 2000 and 2009 and continues to rise. Currently, there is no cure. Standard treatment involves daily injections of insulin and rigorous management of diet and lifestyle.
Phase I/II clinical trials are designed to assess basic safety and efficacy of therapies never before tested in humans, uncovering unforeseen risks or complications. Unpredictable outcomes are possible. Such testing is essential to ensure that the new therapy is developed responsibly with appropriate management of risks that all medical treatments may present.
“This is not yet a cure for diabetes,” said Henry. “The hope, nonetheless, is that this approach will ultimately transform the way individuals with Type 1 diabetes manage their disease by providing an alternative source of insulin-producing cells, potentially freeing them from daily insulin injections or external pumps.”
This clinical trial at UC San Diego Health System was launched and supported by the UC San Diego Sanford Stem Cell Clinical Center. The Center was recently created to advance leading-edge stem cell medicine and science, protect and counsel patients, and accelerate innovative stem cell research into patient diagnostics and therapy.
To learn more about eligibility for this clinical trial, call Todd May at 858-657-7309.
Fragmented REM sleep may hinder effective treatment of mental health condition
The effectiveness of post-traumatic stress disorder (PTSD) treatment may hinge significantly upon sleep quality, report researchers at the University of California, San Diego School of Medicine and Veterans Affairs San Diego Healthcare System in a paper published today in the Journal of Neuroscience.
“I think these findings help us understand why sleep disturbances and nightmares are such important symptoms in PTSD,” said Sean P.A. Drummond, PhD, professor of psychiatry and director of the Behavioral Sleep Medicine Program at the VA San Diego Healthcare System. “Our study suggests the physiological mechanism whereby sleep difficulties can help maintain PTSD. It also strongly implies a mechanism by which poor sleep may impair the ability of an individual to fully benefit from exposure-based PTSD treatments, which are the gold standard of interventions.
“The implication is that we should try treating sleep before treating the daytime symptoms of PTSD and see if those who are sleeping better when they start exposure therapy derive more benefit.”
PTSD is an often difficult-to-treat mental health condition triggered by a terrifying event. It is frequently associated with persons who have served in war zones and is characterized by severe anxiety, flashbacks, nightmares and uncontrollable thoughts, often fearful. Research has shown that fear conditioning, considered an animal model of PTSD, results in disruption of animals’ rapid eye movement (REM) sleep – periods of deeper, dream-filled slumber. Fear conditioning is a form of learning in which the animal model is trained to associate an aversive stimulus, such as an electrical shock, with a neutral stimulus, such as a tone or beep.
Drummond and colleagues investigated the impact of fear conditioning – and another form of behavioral training called safety signal learning – upon human REM sleep, using 42 healthy volunteers tested over three consecutive days and nights. Safety signals are learned cues that predict the non-occurrence of an aversive event.
“We examined the relationship between REM sleep and the ability to learn – and consolidate memory for – stimuli that represent threats and that represent safety,” said Drummond.
“In PTSD, humans learn to associate threat with a stimulus that used to be neutral or even pleasant. Often, this fear generalizes so that they have a hard time learning that other stimuli are safe. For example, a U.S. Marine in Iraq might suffer trauma when her personnel carrier is blown up by road side bomb hidden in trash alongside the road. When she comes home, she should learn that trash on the side of I-5 does not pose a threat – it’s a safe stimulus – but that may be difficult for her.”
The researchers found that increased safety signaling was associated with increased REM sleep consolidation at night and that the quality of overnight REM sleep was related to how well volunteers managed fear conditioning.
Drummond said stimuli representing safety increased human REM sleep and that “helps humans distinguish threatening stimuli from safe stimuli the next day. So while animal studies focused on learning and unlearning a threat, our study showed REM sleep in humans is more related to learning and remembering safety.”
He noted, however, that the findings are not conclusive. No comparable animal studies, for example, have examined the relationship between safety and REM sleep. Nonetheless, the findings do encourage further investigation, eventually into human PTSD populations where fear, safety and sleep are on-going and paramount concerns among military veterans and others.
“A very large percentage of missions in both Iraq and Afghanistan were at night,” said Drummond, who is also associate director of the Mood Disorders Psychotherapy Program at VA San Diego Healthcare System. “So soldiers learned the night was a time of danger. When they come home, they have a hard time learning night here is a time to relax and go to sleep.”
Scientists show bad androgen receptor impairs body’s ability to dispose of damaged cells
Researchers at University of California, San Diego School of Medicine have identified the mechanism by which a rare, inherited neurodegenerative disease causes often crippling muscle weakness in men, in addition to reduced fertility.
The study, published August 10 in the journal Nature Neuroscience, shows that a gene mutation long recognized as a key to the development of Kennedy’s disease impairs the body’s ability to degrade, remove and recycle clumps of “trash” proteins that may otherwise build up on neurons, progressively impairing their ability to control muscle contraction. This mechanism, called autophagy, is akin to a garbage disposal system and is the only way for the body to purge itself of non-working, misshapen trash proteins.
“We’ve known since the mid-1990s that Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are caused by the accumulation of misfolded proteins that should have been degraded, but cannot be turned over,” said senior author Albert La Spada, MD, PhD and professor of pediatrics, cellular and molecular medicine, and neurosciences. “The value of this study is that it identifies a target for halting the progression of protein build-up, not just in this rare disease, but in many other diseases that are associated with impaired autophagy pathway function.”
Of the 400 to 500 men in the U.S. with Kennedy’s disease, the slow but progressive loss of motor function results in about 15 to 20 percent of those with the disease becoming wheel-chair bound during later stages of the disease.
Kennedy’s disease, also known as spinal and bulbar muscular atrophy, is a recessive X-linked disease men inherit from their mother. Women don’t get the disease because they have two copies of the X chromosome. The genetic abnormality causes men to produce a mutant androgen receptor protein, which impairs the body’s sensitivity and response to male sex hormones, sometimes resulting in testicular atrophy and enlargement of male breasts.
In experiments with mice, scientists discovered that the mutant androgen receptor protein besides disrupting male reproductive biology also deactivates a protein called transcription factor EB (TFEB) that is believed to be a master regulator of autophagy in nerve and other cell types.
Specifically, the mutant androgen receptor protein in Kennedy’s disease binds to TFEB and blocks its ability to mediate the break-down and removal of non-working proteins and aggregated proteins.
“Our study tells us that if we can find a way to keep TFEB working, we likely can prevent this disease and others like it from progressing,” La Spada said. “We now have a target for new therapies to treat not only Kennedy’s disease, but also many more common neurological disorders.”
Regional project awarded nearly $6 million Health Care Innovation grant
Approximately 84 million people in the United States suffer from some form of cardiovascular disease, and about 720,000 Americans have a heart attack every year, which works out to one every 44 seconds. To address these alarming statistics, the Be There San Diego Initiative has been awarded a $5.8 million Health Care Innovation grant for a coalition project to help reduce heart attacks and strokes in San Diego County.
The Initiative’s program, San Diego: A Heart Attack and Stroke Free Zone, is a regional collaboration of health care organizations and stakeholders to improve health care delivery and patient outcomes.
The goal during the three year project is to enroll 4,000 high risk patients and lower their blood pressure and cholesterol levels through evidence-based practices and a better understanding of the importance of treatment adherence. The project will also promote heart attack and stroke prevention measures, test novel, cost-effective technology solutions and provide educational opportunities both for patients and within the physician community.
Partners in the Be There Initiative include UC San Diego Health System, Arch Health Partners, Scripps Health, Sharp HealthCare, Kaiser Permanente, Palomar Medical Center, Naval Medical Center, Veterans Administration, the San Diego County Medical Society Foundation, the County of San Diego Health and Human Services Agency, community clinics and others. UC San Diego Health System serves as the fiscal agent for the project.
“Health organizations that are competitive in the market will be working together for the benefit of San Diego patients,” said Anthony DeMaria, MD, principal investigator of the Heart Attack and Stroke Free Zone program and cardiologist at UC San Diego Health System. “This approach will decrease our community’s risk for cardiovascular disease and could result in saving millions in the county by preventing half of the heart attacks and strokes that would have otherwise occurred in the participating patient population.”