Due to the current Public Health Crisis, we are operating with limited staffing and will be focusing on helping patients through the hotline. Because hotline services are restricted to patients, for the time being, we kindly ask pharmacies, providers, and their staff to use our Pharmacy and Provider Portals during this time. If you have a question that cannot be answered by visiting the portal, please send an email to grants@healthwellfoundation.org. We appreciate your patience and look forward to continuing to serve you.

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What Are Movement Disorders?

Real World Health Care_____________________________________________________________________

Throughout 2020, Real World Health Care will focus on Movement Disorders. Movement disorders are related to the nervous system. They include a variety of neurological conditions that cause increased, abnormal movements (voluntary or involuntary) or reduced, slow movements. Some movement disorders are inherited, while others are caused by infection, medication or disease. Several movement disorders are quite rare. In this column, we will provide an overview of several movement disorders, to help you understand what they are, what causes them, and how they may be treated.

What is Chorea?
Chorea is an abnormal involuntary movement disorder caused by overactivity of the neurotransmitter dopamine in areas of the brain that control movement. It is one of a group of neurological disorders called dyskinesias. Chorea is characterized by brief, irregular contractions that are not repetitive or rhythmic, but appear to flow from one muscle to the next. The condition occurs with athetosis, which adds twisting and writing movements. Chorea is a primary feature of Huntington’s Disease but may also occur in a variety of other conditions. It also can be induced by drugs, metabolic and endocrine disorders, and vascular incidents. A small percentage of children and adolescents who have had rheumatic fever may also get a form of chorea called Sydenham’s chorea.

There is no standard treatment for chorea. Treatment and prognosis depend on the type of chorea and the associated disease. However, Sydenham’s chorea is treatable and curable.

For more information on Chorea, visit the Hereditary Disease Foundation.

What is Huntington’s Disease?
Huntington’s Disease (HD) is an inherited disease that causes nerve cells in certain parts of the brain to die. This includes nerve cells that help to control voluntary movement. HD symptoms such as uncontrolled movements, clumsiness and balance problems typically appear in middle age, between 30 and 50, and progressively get worse. Eventually, HD can take away a person’s ability to walk, talk and swallow. Changes in behavior, emotion, judgment and cognition are also common. Some people stop recognizing family members, while others are aware of their environment and can express emotions.

There is currently no cure for HD. Medicines can help manage some of HD’s emotional and movement problem symptoms but cannot slow down or stop the disease. People with HD usually die within 10 to 30 years following symptom onset, most commonly from infections like pneumonia and injuries related to falls.

For more information on Huntington’s Disease, visit the Huntington’s Disease Society of America.

What is Parkinson’s Disease?
Parkinson’s Disease (PD) is a progressive neurodegenerative disease that happens when nerve cells in the brain don’t produce enough dopamine, resulting in abnormal nerve firing patterns within the brain that cause impaired movement. While some cases of PD are genetic, most do not run in families. It is thought that exposure to chemicals in the environment may play a role. PD is more common in men than in women.

Symptoms begin gradually, around age 60, and are often mild, occurring on one side of the body. Later symptoms affect both sides and, as they get worse, people experience trouble walking, talking, chewing and swallowing, or doing simple tasks. Common symptoms include:
• Trembling of hands, arms, legs, jaw and face
• Stiffness of the arms, legs and trunk
• Slowness of movement
• Poor balance and coordination

There is no cure for PD. A variety of medicines sometimes help symptoms dramatically. Surgery and deep brain stimulation can help severe cases.

For more information about Parkinson’s Disease, visit the American Parkinson Disease Association and the National Parkinson’s Foundation.

What is Tardive Dyskinesia?
Tardive dyskinesia (TD) is a neurological disorder that involves involuntary movements such as facial grimacing, finger movement, rocking or thrusting the pelvis, jaw swinging, repetitive chewing, rapid blinking, tongue thrusting and restlessness. It is a serious side effect that occurs when taking medicines called neuroleptics, which are antipsychotics or major tranquilizers used to treat mental health problems. TD often occurs when such drugs are taken for many months or years, but in some cases, it occurs after taking them for as little as six weeks.

After TD is diagnosed, a patient’s health care provider may recommend stopping the medicine slowly or switching to another one, which may help to reverse the condition. However, even if the medicine is stopped, the involuntary movements may become permanent or even worse. Various medicines are available to treat mild and moderate TD, and deep brain stimulation may be tried for severe forms of TD.

For more information on TD, visit Mental Health America or the National Institute of Mental Health.

What is Tourette Syndrome?
Tourette Syndrome (TS) is a disorder of the nervous system. People with TS make sudden, unusual movements or sounds called tics. Common tics include throat-clearing, blinking, facial grimacing, shrugging one’s shoulders, jerking one’s arms and occasionally repeating words or blurting out swear words. Those with TS have little or no control over their tics, which usually start in childhood and may be worse in the early teen years. Many people eventually outgrow them, although 10-15 percent of those affected have a progressive or disabling course that lasts into adulthood.

TS is more common in boys than in girls and its cause is unknown. More than 85 percent of children diagnosed with TS also have been diagnosed with at least one additional mental, behavioral or developmental condition, most commonly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). No treatment is needed unless the tics interfere with everyday life. Excitement or worry can make tics worse. Calm, focused activities may make them better. Medicines and talk therapy may also help when symptoms interfere with functioning.

For more information about TS, visit the Tourette Association of America.

Resources:
Centers for Disease Control and Prevention
Mayo Clinic
National Institutes of Health

Read this article online at Real World Health Care.

Special Report: Managing Your Mental Health During the COVID-19 Crisis

Real World Health Care_____________________________________________________________________

By now, most Americans are familiar with the physical symptoms of COVID-19, including cough, fever, and shortness of breath. However, coronavirus fears and COVID-19 diagnoses can cause more than just respiratory illness. They can lead to a range of mental health issues as well, including isolation, anxiety and stress.

According to experts at Mental Health America (MHA), the mental health impacts of the COVID-19 health crisis are a critical factor to consider for all people. They note that the effects linger for those who lose loved ones and for those whose anxiety, post-traumatic stress, and other serious conditions are left untreated. MHA cautions: “We will pay a price if we don’t take all of this seriously from the start.”

Mental Health Resources
Our valued partners, Mental Health America and the Anxiety and Depression Association of America (ADAA), have compiled a number of expert tips, along with relevant information and resources, to assist those coping with anxiety and other mental health issues relating to the coronavirus outbreak. Everyone at Real World Health Care and our founding sponsor, the HealthWell Foundation, thanks these two organizations for taking leadership roles to address the very real mental health consequences of this pandemic. Please visit the links below.

Coronavirus Anxiety – Helpful Tips and Resources, from the ADAA.

Mental Health and COVID-19 – Information and Resources, from MHA.

Financial Distress
Like with many chronic and life-altering diseases, a diagnosis of COVID-19 can cause financial stress for families—stress that may manifest itself both physically and mentally. As a testament to its commitment to placing the needs of its patient communities first and foremost, the HealthWell Foundation has opened a new fund to assist individuals who are at risk or have been quarantined due to COVID-19.

For questions regarding HealthWell’s COVID-19 Ancillary Costs Fund or to learn how to support this initiative, please email COVID19@HealthWellFoundation.org.

Read this article online at Real World Health Care.

Search & Destroy: Chimeric Antigen Receptor T-Cells (CAR-T)

Real World Health Care_____________________________________________________________________

By Emily Burke, PhD, Director of Instruction, Biotech Primer

Editor’s Note: The following article is reprinted, with permission from Biotech Primer. The original version appeared in the Biotech Primer WEEKLY. To subscribe to the Biotech Primer WEEKLY, click here.

Emily Burke, PhD

Emily Burke, PhD, Director of Instruction, Biotech Primer

The first (and so far, only) chimeric antigen receptor T-cell (CAR-T) therapies—tisagenlecleucel and axicabtagene ciloleucel were approved in 2017, and they remain one of the hottest types of immunotherapies on the market today. They work by boosting the body’s ability to recognize and attack cancer cells. This column reviews the basics of CAR-T technology and takes a peek at CAR-T innovations moving through the pipeline.

Term of the Week: Killer T-Cells

CAR-T therapy is based on a type of white blood cell called a killer T-cell. The job of these cells is exactly what the name implies — to kill dangerous cells. They target diseased cells in the body via cell-surface receptors: each has a uniquely shaped receptor and recognizes its intended target because the shape of its receptor “matches” or fits into a uniquely shaped surface protein found only on diseased cells. Once the killer T-cell “docks” onto its target, it injects an enzyme which triggers death. The result: no more bad cells.

Killer T-Cells In Action

Why CAR-T?

In theory, our immune system should recognize the unique proteins presented on cancerous cells. However, there are two main reasons this doesn’t always happen:

  1. Early on in tumor development, the cell composition is similar enough to healthy tissue that it can be overlooked by the immune system.
  2. Later, as a tumor progresses, it releases chemical signals that suppress the immune response, helping it to evade detection. This trickery is known as the tumor microenvironment and once again the dangerous cancer cells can pass by undetected.

So what’s a scientist to do?  Figure out a way to train killer T-cells to ALWAYS recognize and destroy cancer cells…enter CAR-T.

How to Train an Immune System

CAR-T therapies boost the body’s ability to recognize and attack cancer cells. These “super” killer T-cells have been physically enhanced to go after cancer. Like the mythical chimera, this drug is composed of different parts. Genetic engineers fuse an antibody with a killer T-cell receptor to create a chimeric molecule—the “C” in CAR-T.

The transformation begins with technicians removing killer T-cells from a patient’s body and isolating them in the lab. Next, scientists use a viral vector—a virus that has been modified to contain a therapeutic gene—to deliver a gene that encodes the chimeric receptor to the T-cells.

The enhanced receptor includes two parts: a targeting domain and an activation domain. The first is the portion that remains on the surface of the T-cell. It’s an antibody that detects and locks onto a specific surface protein on the patient’s malignant cells. The activation domain part of the receptor is triggered once the targeting domain attaches itself to the desired cancer protein.

Chimeric Antigen Receptor (CAR)

The engineered T-cells are then reinfused into the patient, at which point the targeting domain finds the proper surface protein on the tumor cell and attaches to it. Then, the activation domain signals the killer T-cell to:

  • Stay alive.
  • Make copies of itself (replicate).
  • Release cytokines—chemical signals that activate other white blood cells to assault the tumor.
  • Kill the target cell.

CAR-T Therapy

What’s in a Name?

Chimeric antigen receptor therapy broken down:

  • Chimeric: Composed of components from two distinct parts, such as an antibody and a killer T-cell.
  • Antigen: A protein that is recognized by an antibody, such as a protein on the surface of a tumor cell.
  • Receptor: A protein that is embedded in a cell membrane and transmits signals to itself in response to being activated, for example a T-cell receptor transmits signals to the T-cell when it docks onto its target.
  • Therapy: A treatment meant to manage or cure a disease

Tricky Terminology

The medical community classifies CAR-Ts as a “cell-based gene therapy.” They’re immune cells that have been engineered using gene therapy techniques.

Next-Generation CAR-T

The current generation of CAR-Ts have the potential to cause serious safety issues in some patients. While highly effective against blood cancers, their results have been less impressive when targeting solid tumors. Finally, existing CAR-T therapies are patient-specific, which adds to their expense and the time required for their production. Let’s take a look at each of these issues in turn and examine some steps that are being taken to address them.

Eye of the Storm

One of the reasons CAR-T treatments are so powerful is because once activated, they multiply inside of the body, and release inflammatory molecules called cytokines. Cytokines serve two core functions:

  • They activate additional white cells to fight pathogens.
  • They stimulate white blood cells to move towards inflammation.

Cytokine signaling makes for a quick, strong, and usually appropriate immune response via a positive feedback loop in which activated white cells release more activating cytokines. The response typically dissipates when the pathogenic cells have been destroyed. However, sometimes the feedback loop just keeps looping. This phenomenon is called a cytokine storm, and leads to acute inflammation with high fever, swelling, and/or nausea. It sometimes causes serious tissue damage and even death. For example, excess fluids can seep into the lungs and cause them to fail. Although uncommon, cytokine storms pose the biggest risk of CAR-T treatments.

Calming the Storm

Tocilizumab has been approved for the treatment of cytokine storms in patients undergoing CAR-T treatments. The drug is a monoclonal antibody therapy designed to “mop up” excess interleukin 6, an inflammatory cytokine.

Biopharma companies are also working on new CAR-T treatments with controls to regulate cytokines and minimize storms. First generation CAR-T therapies induce maximum white cell activity—a full cytokine barrage. Their intensity makes tamping down the cytokine response impossible.

In one example of next generation therapy, patients take an adjunct small molecule drug during their CAR-T infusion. This sidekick medicine provides an on/off switch for the CAR-T therapy. It turns on the therapy to fight the cancer. Should a cytokine storm ensue, doctors can immediately withdraw the adjunct drug, turning off CAR-T and ultimately stopping cytokine release.

Solid Tumors

So far, CAR-T has proven most effective against blood cancers. Targeting solid tumors is more difficult, in large part because tumors contain cells that secrete anti-inflammatory cytokines, or cytokines that turn the immune response down. Solid tumors can also be difficult to penetrate, meaning CAR-Ts can’t always effectively access malignant cells on the tumor’s interior.

One way to combat this immunosuppressive environment is to engineer CAR-Ts to secrete specific inflammatory cytokines designed to beef up their ability to attack solid tumors. One turbo-charged CAR-T in development releases interleukin 12 when triggered. Interleukin 12 is a cytokine known to combat the tumor’s immunosuppressive environment. When combined with small molecule controls for safe activation of the CAR-T, this immune-activating protein should be released in a safe and controlled manner.

Natural Killers

Another approach to targeting solid tumors with CAR technology is to use a different type of white blood cell that more easily penetrates solid tumors. Enter natural killer (NK) cells. These white blood cells are a part of our innate immunity, or the immune response that is activated immediately in response to any threat. Most immunologists think that NK cells play a role in recognizing and killing off cancer cells that arise in our body and are able to more easily penetrate solid tumors. However, early-stage cancers often aren’t recognized as a threat. By modifying NK cells with a CAR that targets them to a specific tumor type, their killing ability can be put to work. CAR-NK therapies are now in Phase I/II clinical studies for B-cell malignancies.

Chowing Down on Cancer

Macrophages are our body’s scavengers. The name derives from a Greek phrase meaning “big eater.” These cells kill infectious or diseased cells by surrounding and digesting them. Think of a sloppy Pacman. After a macrophage meal, minute bits of foreign cell proteins or antigens remain on its surface. The leftovers help activate some of the immune system’s other defenses, such as killer T-cells.

Biopharma companies are carrying out preclinical development of CAR-macrophages to destroy specific cancer cells. The amped up macrophages will simultaneously trigger other immune cells to recognize and attack those same antigen-bearing cells. Like other macrophages, CAR-macrophages can penetrate solid tumors much more effectively than basic T-cells.

Off-the-Shelf CAR-T

First generation CAR-T has been patient-specific, or autologous. In other words, T-cells are first removed from the patient to be treated, modified, and infused back in. Customizing CAR-T in this manner is time consuming and expensive but necessary to avoid immune rejection.

A few different companies are exploring ways to create allogeneic or “off the shelf” T-cell therapies that can be used with any patient. The trick is to remove the telltale signs that allow the recipient’s immune system to recognize the engineered T-cell as foreign. Strategies in preclinical development use genome editing to remove the genes responsible for immune rejection.

We’re still wowed by first-generation CAR-T, but biopharma companies have safer, more effective, and more versatile second-generation therapies coming down the pipeline. We’ll be watching their development closely.

Read this article online at Real World Health Care.

 

 

People with Macular Degeneration Live Full Lives with Help from Ophthalmologists

Real World Health Care_____________________________________________________________________

Does a diagnosis of age-related macular degeneration (AMD) mean you can’t live a rich, fulfilling life? Not necessarily, according to the experts.

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Purnima S. Patel, MD, Emory University

“The initial diagnosis can be scary,” said Purnima S. Patel, MD, associate professor of ophthalmology at Emory University who also works at the Atlanta VA Medical Center and serves as a clinical spokesperson for the American Academy of Ophthalmology. “People hear about the in-eye injections that are standard therapy and think, ‘there’s no way I can do this.’ They should know that their ophthalmologist can help them adapt to their situation and make the most of their vision. Plus, those injections aren’t nearly as gruesome as everyone fears.”

Start Screening for Macular Degeneration Early

As its name suggests, AMD is a product of aging. The most common form of AMD, dry AMD, happens when parts of the eye’s macula (part of the retina) get thinner with age. Tiny clumps of protein called drusen grow and central vision is slowly lost. The less common, but more serious, wet AMD happens when abnormal blood vessels grow under the retina and leak blood or other fluids that cause scarring on the macula. Vision loss is faster with wet AMD than with dry AMD.

The most common symptoms of AMD are vision distortions: straight lines that look wavy or bent, “splotchy” looking central vision, or being able to see some things but not others. Side, or peripheral, vision is not affected by AMD.

“Patients may have these symptoms and not even know it,” Dr. Patel said. “That is why we encourage adults to visit an ophthalmologist for a baseline screening at around age 40, when eye conditions start to manifest. By age 65, people should be screened annually.”

Dr. Patel added that annual screenings are particularly important for people with high risk factors, including a family history of AMD, light skin, smoking, being overweight, and having high blood pressure, high cholesterol or heart disease.

“The best prognosis for maintaining or recovering your vision is based on the strength of your vision at the time of diagnosis,” she said. “An ophthalmologist can stay attuned to any nuanced changes.”

Macular Degeneration Treatments: What to Expect

According to Dr. Patel, there is no cure for dry AMD. However, she typically recommends that patients with this common form of AMD take a vitamin formulation known as AREDS-2. Clinical studies of AREDS show that the formulation may delay progression of advanced AMD and help maintain vision longer in patients with intermediate AMD or AMD in one eye.

She also recommends an eye-healthy diet including lots of leafy greens, not smoking, and wearing UV eye protection, even on cloudy days—advice applicable to those with both dry and wet AMD.

“Ophthalmologists may send patients home with an Amsler grid,” she added. “It lets patients monitor each eye to help detect those subtle vision changes that aren’t always obvious because they come about so slowly.”

Treatments for wet AMD have evolved significantly over the past 10 years, according to Dr. Patel. Today, the standard therapy involves monthly injections of anti-VEGF drugs, which help reduce the number of abnormal blood vessels in the retina and slow blood vessel leakage.

“These injections aren’t a cure, but they can control and stabilize vision loss,” she said. “Your ophthalmologist will apply a sterilization solution to prevent infection as well as numbing drops before inserting a very slender needle into the eye. The whole process is a lot less painful than most people fear.”

Dr. Patel added that some patients report a gritty or sandy feeling in the eye following injections, but most people can go about their daily activities immediately after treatment as long as they avoid getting their eye dirty—so no swimming or lawn mowing, for example.

Living with Macular Degeneration

According to Dr. Patel, most people with macular degeneration live full lives, with minimal impact on activities of daily living.

“Because the central vision is affected, activities like reading and watching TV can be challenging,” she said. “However, since peripheral vision isn’t affected, people can still get around.”

She encourages those with MD to ask their ophthalmologist about assistive devices such as magnifiers and other tools and electronics designed specifically for those with low vision.

“I take care of people with macular degeneration every day and I’m in awe of the amount of resilience they have and the way they continue to thrive with the various treatment options and tools at our disposal,” concluded Dr. Patel.

 

American Macular Degeneration Foundation Piecing Together the Puzzle of Age-Related Macular Degeneration

Real World Health Care_____________________________________________________________________

Macular degeneration is the leading cause of vision loss and blindness in those over 55. According to the American Macular Degeneration Foundation (AMDF), it affects more than 10 million Americans.  After the age of 75, one in three Americans is at risk of developing this incurable disease.

While the cause of age-related macular degeneration (AMD) remains unknown, multiple, interconnected factors contribute to its development, including heredity, biological processes, age and environmental/lifestyle factors. Scientists are beginning to solve the puzzle of this complex disease, thanks in part to research funded by the AMDF.

“AMDF is committed to preventing, treating and curing macular degeneration through our national research agenda,” said Jennifer Williams, director of marketing for the AMDF. “At the same time, we offer hope and support to those with AMD and their families by raising public awareness of the disease, lobbying for increased federal research funding, and providing individualized educational resources.”

Age-Related Macular Degeneration Fueled by Nature and Nurture

AMDF takes a “broad impact” approach to the research it funds, supporting studies that significantly advance the likelihood of new treatments, unveil useable information about modifiable lifestyle factors associated with the disease, or create new opportunities to improve quality of life for all people affected by AMD.

“Minimizing the risk of developing AMD or slowing its progression requires a whole-body approach, rather than simply protecting your eyes with sunglasses,” explains Matthew Levine, AMDF Grants, Advocacy and Partnerships. “It involves creating a healthy balance between nature and nurture. While people may be born with certain genes that are associated with AMD, the extent to which those genes come into play is impacted by our environment and controllable behavior, including what we eat, how much we exercise, and whether or not we smoke.”

Biological Processes “Gone Wrong”

According to Levine, the current standard of care for treating wet AMD (the late-stage form of the disease that produces sudden, irreversible vision loss) is a routine, often monthly, injection of anti-VEGF (vascular endothelial growth factor) therapy into the eye, which suppresses the development of leaky, “rogue” blood vessels that can cause permanent damage to the eye’s rods and cones. Some patients find it difficult to adhere to the monthly injection schedule, and a significant percentage of patients don’t seem to respond to the therapy.

“Anti-VEGF therapy is currently considered the ‘last line of defense,’ and as a patient, it can be devastating to find out that you’re not responding to treatment as hoped,” said Levine. “However, recent research suggests that the ‘non-responders’ to anti-VEGF therapy aren’t really non-responders at all. Instead, these patients are responding earlier, and the drug is active for a shorter duration.  A different, individualized treatment plan for this group of AMD patients may save the sight millions of people.  This is an example of the type of broad impact research that AMDF seeks to support and may ultimately lead to a new understanding of how individualized this disease may be.”

Treating AMD with Gene Therapy

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Johanna Seddon, University of Massachusetts Medical School

Researchers are continuing to identify and study the role of genes that are associated with degenerative diseases of the retina. The AMDF has funded a number of research projects in this area, notably the work of Johanna Seddon, MD, ScM, Department of Ophthalmology & Visual Sciences, University of Massachusetts Medical School, whose ground-breaking findings of AMD-related genes and their interactions with environmental factors (nutrition, smoking, body mass, etc.) have formed the basis for today’s early AMD management. Dr. Seddon is also co-author of AMDF’s “Eat Right for Your Sight,” a science-based cookbook for healthy eating to preserve vision.

Another AMDF-supported researcher,  Neena Haider, PhD, Associate Professor of Ophthalmology at Harvard Medical School and Associate Scientist with the Schepens Eye Research Institute, has also broken new ground. Her work has resulted in the first FDA approval of a gene “modifier” therapy that doesn’t rely on knowing and replacing the exact genetic mutation involved in a disease, but rather the gene that controls the entire cascade of biological events that leads to the diseased state.

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Neenah Haider, Harvard Medical School & Schepens Eye Research Institute

“Macular degeneration is different from many other diseases because multiple genes seem to play a role in the disease’s development,” said Dr. Haider. “In fact, we’re still trying to understand which genes, out of about 2,000, cause AMD and how those genes can be modified to prevent AMD.  By modulating a gene that controls the pathways for inflammation, oxidative stress and protection from cell death, we can restore cells to their healthy state and prevent disease.”

Early AMD Detection

Levine noted that gene modifier therapies and other, new treatment approaches may prove to be particularly valuable when AMD is caught early, before the development of waste deposits beneath the retina, known as drusen, which are currently considered the earliest indicators of AMD. Recent research has established that the earliest indicator of AMD is the inability to quickly adapt to dark environments, as when entering a darkened theater on a bright day. Most people’s eyes adapt fairly quickly, but in those with AMD, the adaptation period is quite prolonged, making it difficult, for instance, to drive at night against oncoming headlights followed by a stretch of unlit road.

“Testing for compromised dark adaptation can detect AMD up to three years before the appearance of drusen, before patients experience any changes in their field of vision and central sight, and can allow patients to start making healthy lifestyle choices,” said Levine. “As with any progressive disorder, early detection and intervention can slow progression and, in the case of AMD, preserve sight.”

Precision Medicine Approach to AMD

The AMDF also is supporting Dr. Haider’s work in two other areas. One focuses on developing retina organoids —retina cell groupings grown from an individual patient’s blood or skin cells that are then turned into stem cells. These “retinas in a dish” will be used to test personalized medicine therapies with both FDA-approved and novel agents. The other area of research focuses on uncovering relevant “signatures” of patients’ microbiomes — the collection of microorganisms that inhabit our bodies and play a significant role in disease.

“The microbiome is unique to both individuals and sub-populations and is something you can change with diet and lifestyle choices,” Dr. Haider explained. “It’s another good example of how we can approach, attenuate and treat a disease by focusing on both our genetics, or nature, and our environment, or nurture.”

Immunotherapy for AMD

The AMDF also is supporting research into the role of the immune system in regulating AMD, through grantee Kip Connor, PhD, Associate Professor of Ophthalmology at Harvard Medical School and Associate Scientist at Massachusetts Eye and Ear. According to Dr. Connor, the body’s immune system is vital not only in staving off infection, but also in helping clear our own body’s cells that have been damaged due to stress or injury.

Real World Health Care - ADMF - Connor

Kip Connor, Harvard Medical School

“This is especially important in the brain, of which our retina is a part,” he explained. “If a retinal neuronal cell dies, we cannot make more, so when these cells become injured our immune system has to carefully remove them so they don’t injure their neighboring cells. Once we lose a neuron, we cannot replace it like other cells in our body, so keeping these cells around as long as possible is vital to maintaining our vision.”

Dr. Connor added that as we age, these immune regulatory systems can become dysfunctional or overactive, which drives the disease pathology and the resultant loss of vision. He pointed to a number of immune pathways that are being investigated in the pathology of AMD, including one of the oldest evolutionally conserved immune pathways, the Complement system. The Complement system has been implicated as a risk factor for AMD, with a 50 percent increased risk of developing the disease in individuals with a mutated form of one of the proteins in the pathway. More recently, the role of resident immune system scavenger cells of the retina, microglia, has become an area of intense investigation, including how these cells become activated — and when — throughout the disease course.

Stem Cell Treatments for AMD and Beyond

According to Levine, AMDF-supported scientists and others are developing stem cell replacement therapies for the retinal pigment epithelium (RPE), the tissue behind the retina that provides the retina with nutrition and removes debris generated by the eyes’ photoreceptor cells. Patient-derived, lab-grown RPE cells are placed into a biologically based “scaffolding” that is surgically implanted behind the retina to create and maintain a better environment for the photoreceptor cells.  Recently, the National Eye Institute (NEI) announced the first human clinical trial to test the safety of this approach to treat geographic atrophy, the advanced “dry” form of AMD.

For people with low vision from AMD, artificial retinas may offer hope as well. The artificial retina is a tiny camera and video processor mounted on a pair of glasses, which communicates wirelessly with a sheet of electrodes implanted in the eye. The camera collects light signals and transmits them through the electrodes to the brain, bypassing the damaged retina. The more electrodes, the better the technology works.

From the Lab to the Clinic

While the AMDF’s funding of AMD research is leading to real gains in approved treatments, the Foundation’s Williams noted that an AMD diagnosis is still overwhelming for most patients.

“We’ve conducted surveys about communications between patients and doctors and have found that information about treatments — and especially the important lifestyle modifications that can slow the disease’s progress — isn’t always delivered or received,” she concluded. “Sometimes the advice to eat well, get exercise, wear eye protection and not smoke seems so simplistic that people ignore it, and the disease progresses. The AMDF is developing intiatives to improve treatment outcomes by overcoming those communications obstacles.”

For more information, visit the American Macular Degeneration Foundation and follow Real World Health Care’s coverage of Age-Related Macular Degeneration.

Read this article online at Real World Health Care.

 

Spotlight on Macular Degeneration

Real World Health Care_____________________________________________________________________

By Emily Burke, PhD, Director of Instruction, Biotech Primer Inc.

Editor’s Note: The following article is reprinted with permission from the Biotech Primer WEEKLY newsletter. To subscribe to the WEEKLY, visit www.weekly.biotechprimer.com.

emily_burke_biotechprimer

Emily Burke, BiotechPrimer.com

Getting old is for the birds. Time has its way with nearly every part of us: skin, hair, muscles. Few changes are more alarming, however, than those to our eyes. There’s more to old eyes than bifocals and cataracts though. One of the most common eye diseases is age-related macular degeneration (AMD). It affects more than 13 million people over age 50 in the United States. It’s the leading cause of vision loss in this age group.

 

Eyes are spectacularly complicated organs: they contain over two million moving parts. You know some of the basics: iris, pupil, lens, retina. In some ways, this last, the retina, is more accurately considered part of the brain.

Term of the Week: Retina

The retina is composed of light-sensitive nervous tissue which forms a thin membrane that lines the rear two-thirds of the eyeball. It takes in light from the world around and converts into neural signals that travel along the optic nerve to the brain, telling us — “Hey, there’s an apple, or a laptop, or whatever.”

The anatomy of the eye (The National Eye Institute)

The macula is the small central area of the retina that enables central, high-resolution, color vision.

Macular Degeneration: A Gradual Loss of Vision

Macular degeneration progressively devastates eyesight, causing blurred vision and blocking the center of a person’s visual field. What begins as a minor annoyance ends up making everyday tasks such as reading and driving impossible.

Ophthalmologists and other scientists don’t know exactly what causes AMD. It is however, associated with a buildup of proteins and lipids just beneath the retina. These deposits, drusen, are a normal part of aging. However, the presence of larger or more drusen raises the risk of AMD. As the disease progresses, vision decreases. There are two types of AMD: neovascular (wet) or atrophic (dry).

Wet Age-Related Macular Degeneration (AMD)

In wet AMD, the infiltration of excess blood vessels is the main culprit. These abnormal vessels often leak fluid and blood, injuring the retina. Wet AMD progresses quickly, leading to loss of central vision without treatment. This form of the disease accounts for about 10 percent of cases.

FDA-approved treatments for wet AMD include Ranibizumab, Brolucizumab, and Aflibercept. These work by mopping up excess vascular endothelial growth factor (VEGF), which is what causes the excess blood vessel growth. Ranibizumab and Brolucizumab are monoclonal antibodies specific for VEGF. Aflibercept consists of the VEGF-receptor fused to the constant region of an antibody for stability. Similar to a mAb, this combination is called a fusion protein. It’s highly specific for VEGF, binding it before it reaches its intended receptor on the surface of blood vessels. These VEGF-blocking treatments effectively stop the progression of AMD, but don’t cure it.

KS-301 is an antibody-biopolymer conjugate (ABC), which also targets VEGF. An ABC is an antibody with a biopolymer—a chain of repeating subunits produced by a living organism—attached. In KS-301, the repeating subunits are lipids. They make the antibody more stable. That means patients can go up to five months between injections, compared to one month (Ranibizumab), two months (Aflibercept), or two to three months (Brolucizumab). The treatment is now in Phase II/III development.

These therapies are injected in the patient’s eye, which makes them understandably unappealing. As an alternative, PAN-90806 is a small molecule inhibitor of VEGF that patients can administer at home by eyedrop. The drug has completed Phase I clinical studies.

It may be possible to do away with repeated treatments altogether with gene therapy. RGX-314 delivers a gene encoding an anti-VEGF antibody. In Phase I/II studies, participants produced the therapeutic protein, which controlled VEGF levels.

Dry Age-Related Macular Degeneration (AMD)

Dry AMD involves a gradual breakdown in the macula’s light-sensitive cells. The dry variety progresses much more slowly than wet and accounts for about 90 percent of AMD cases. Advanced dry AMD occurs when cells in regions of the retina have wasted away and died. Sometimes these regions of atrophy (death) look like a map to the physician who is examining the retina, giving rise to the term “geographic atrophy” for late-stage dry AMD.

Currently, no treatments exist for dry AMD. However, some studies suggest that high doses of antioxidants including C and E vitamins, copper, zinc, and beta-carotene may slow its progression.

Inflammation, specifically the activation of complement proteins, is associated with drusen buildup and dry AMD progression. When they’re activated, these immune system proteins interact, destroying targeted cells. Inappropriate activation of complement proteins can result in the destruction of healthy cells and tissue. A number of drugs in clinical development work by inactivating complement proteins:

  • APL-2 is a peptide drug in Phase III development. APL2 binds to complement protein C3 and prevents its interaction with other complement proteins. Preventing this interaction prevents activating their destructive power.
  • Avacincaptad pegol is a DNA aptamer in Phase II development. DNA aptamers are short strands of DNA that bind to a specific protein. Avacincaptad pegol binds to and inhibits complement protein C5.
  • IONIS-FB-LRx is an antisense drug that blocks the production of complement factor B, currently in Phase II clinical testing.

Last month, the National Eye Institute announced preparations to begin clinical testing of stem cells for dry AMD. In the lab, researchers have coaxed stem cells to grow into retinal cells. In rodent and pig models, these cells restored vision, setting the stage for test human testing.

About Biotech Primer Inc.

Biotech Primer Inc. delivers current, relevant training to help professionals understand the science, business and regulatory processes essential to the biotechnology, pharmaceutical, molecular diagnostics and medical device industries. For more information, visit www.biotechprimer.com.

Read this article online at Real World Health Care.

 

Welcoming 2020 with New Insights for Patients with Chronic Diseases

Real World Health Care_____________________________________________________________________

Topics in Focus: ALS, CAR T Therapies, Macular Degeneration and Movement Disorders

The HealthWell Foundation is proud to be a founding sponsor of Real World Health Care. Since 2013, Real World Health Care (RWHC) has brought you compelling content on health care issues facing Americans. From features on the people, programs and products changing the way health care is delivered, to interviews with leading researchers and clinicians, to profiles of patient advocacy organizations, RWHC has provided valuable insights and information to those interested in both the current state and future of health care.

healthwell_foundation_president_krista_zodet

Krista Zodet, President, HealthWell Foundation

This year, RWHC will focus on several chronic diseases of concern to Americans: amyotrophic lateral sclerosis (ALS, commonly called Lou Gehrig’s disease), macular degeneration, and movement disorders including Parkinson’s Disease, Huntington’s Disease, and Tourette. We also will delve into CAR T therapies, which hold promise for changing the lives of countless cancer patients.

As in previous RWHC series, we will be shining a spotlight on organizations and individuals who are dedicated to supporting patients and championing the research needed to improve health outcomes.

An Inside Look at Patient Communities

What is ALS?

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. It progressively affects voluntary muscle action, leading to the potential of total paralysis in patients at the later stages of the disease. ALS usually strikes people between the ages of 40 and 70, and it is estimated that at least 16,000 Americans have the disease at any given time, with more than 5,000 people newly diagnosed each year.

What is Macular Degeneration?

Macular Degeneration is an incurable eye disease that is the leading cause of vision loss, affecting more than 10 million Americans. When the disease progresses, people experience wavy or blurred vision, and if the condition continues to worsen, central vision may be completely lost. People with very advanced macular degeneration are considered legally blind.

What are Movement Disorders?

Movement disorders are a group of nervous system (neurological) conditions that cause abnormal increased movements, which may be voluntary or involuntary. They can also cause reduced or slow movements. There are several types of movement disorders, including (but not limited to):

  • Chorea: characterized by repetitive, brief, irregular, somewhat rapid involuntary movements that typically involve the face, mouth, trunk and limbs.
  • Huntington’s Disease: an inherited progressive, neurodegenerative disorder that causes uncontrolled movements (chorea), impaired cognitive abilities and psychiatric conditions.
  • Parkinson’s Disease: a slowly progressive, neurodegenerative disorder that causes tremor, stiffness, slow decreased movement or imbalance. It may also cause other nonmovement symptoms.
  • Tardive Dyskinesia: a neurological condition caused by long-term use of certain drugs used to treat psychiatric conditions. It causes repetitive and involuntary movements such as grimacing, eye blinking and other movements.
  • Tourette Syndrome: a neurological condition that starts between childhood and teenage years and is associated with repetitive movements (motor tics) and vocal sounds (vocal tics).

CAR T Therapies

One of the newest cancer treatments available to patients today is CAR T-cell (Chimeric Antigen Receptor T cell) therapy. CAR T-cell therapy uses a patient’s own cells and re-engineers them to fight cancer. It is a complex and costly treatment that is only offered at some major cancer centers and often causes very severe side effects. Most patients treated with this personalized immunotherapy have been people with blood cancers.

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Conditions like ALS, macular degeneration, movement disorders and cancer can have a significant impact on patients, their families, friends and entire communities. Real World Health Care seeks to be a source of information and inspiration for everyone touched by these chronic and life-altering illnesses.

I invite you to become part of our community and support patients in need by following RWHC as we cover these topics throughout 2020. Click the Subscribe button on the right side of this page to be notified when new posts publish. You can also follow us on Twitter @RWHCblog.

We want to hear from you! If you are a patient or are working with an organization that supports these patient communities, please let us know. We would be delighted to share your story with our subscribers. Contact us today.

 

Resources and References:

ALS Association

American Macular Degeneration Foundation

Cancer Support Community

Mayo Clinic

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Editor’s Note: Real World Health Care is pleased to close out our 2019 series on migraine by sharing an article originally published by the National Headache Foundation. Here, they share advice for helping patients respond to caregivers and others when faced with stigma associated with migraine disease. You can read the original article here, and learn more about migraines from the National Headache Foundation blog.

It can be difficult to explain the excruciating pain of a migraine to those who don’t experience it. In fact, there’s a stigma attached to this disorder stemming from a lack of knowledge on the severity of symptoms associated with migraine and headache. Migraine is not just a headache, and the attack may include nausea, vomiting and sensitivity to light and sound. Anyone who experiences migraine attacks has surely been frustrated with well-meaning friends and family offering dismissive advice that’s not only unhelpful but can make the situation worse.

We took to social media to discover the most common comments and advice that people with migraine hear when they discuss their condition. We compiled the 10 most common in a list below.

  1. Take some Advil
  2. Did you take something?
  3. Have you been drinking enough water?
  4. You’ve got another headache?
  5. Again?
  6. I get bad headaches too.
  7. It’s just a headache.
  8. I have some Tylenol if you want it.
  9. Just push through it!
  10. I think you just want an excuse.

Chances are, you’ve heard one or more of these pieces of “advice” at some point in your life. One comment in particular—“It’s just a headache”—encapsulates the popular misconception about a disorder that affects around 40 million Americans. It’s frustrating to feel that no one understands what you’re going through, and some, out of their own lack of knowledge, may even think you’re faking symptoms.

In order to demystify the stigma surrounding migraine disease, here are a few steps you can take to educate those around you about this debilitating neurological disorder.

Explain the Migraine Triggers

While migraine triggers differ from person to person, there are a few common causes that will bring about symptoms in many sufferers. For example, a naturally-occurring compound called Tyramine—often found in aged, smoked or cured meats and vegetables—has been found to be a major trigger of migraine attacks. If friends, family and coworkers have a better understanding of your migraine triggers, they’re more likely to notice when you’re experiencing an attack and can respond accordingly.

Provide Migraine Resources

Of course, you don’t need to justify your condition to everyone with whom you interact, but migraine symptoms can cause a strain on certain close relationships. For example, a boss or supervisor doubting the severity of your condition may cause you additional stress, which can negatively impact work performance or compound the pain. Fortunately, the National Headache Foundation has an abundance of resources that help skeptics and allies alike get a better understanding of migraine and headache. Sharing these informative sources with those closest to you can help alleviate the burden of constantly explaining your condition.

Seek Migraine Treatment from a Headache Specialist

Understanding the specifics of your condition makes it far easier to explain them to others. Seek out a headache specialist to receive an appropriate diagnosis. The health care practitioner will likely diagnose you based on your medical history, symptoms and a physical and neurological examination. This could include blood tests, magnetic resonance imaging (MRI) or computerized tomography (CT) scan. (It is critical to visit a medical professional who specializes in headache and migraine, as they will be able to best diagnose and treat the pain.)

There will always be those who doubt the severity of migraine symptoms. However, by educating yourself and those around you, you can help tear down the stigma associated with migraine disease and, in the process, make living with migraine attacks a bit easier.

Read this article online at Real World Health Care.

What People with Migraine Attacks Hate to Hear

Real World Health Care_____________________________________________________________________

Editor’s Note: Real World Health Care is pleased to close out our 2019 series on migraine by sharing an article originally published by the National Headache Foundation. Here, they share advice for helping patients respond to caregivers and others when faced with stigma associated with migraine disease. You can read the original article here, and learn more about migraines from the National Headache Foundation blog.

It can be difficult to explain the excruciating pain of a migraine to those who don’t experience it. In fact, there’s a stigma attached to this disorder stemming from a lack of knowledge on the severity of symptoms associated with migraine and headache. Migraine is not just a headache, and the attack may include nausea, vomiting and sensitivity to light and sound. Anyone who experiences migraine attacks has surely been frustrated with well-meaning friends and family offering dismissive advice that’s not only unhelpful but can make the situation worse.

We took to social media to discover the most common comments and advice that people with migraine hear when they discuss their condition. We compiled the 10 most common in a list below.

  1. Take some Advil
  2. Did you take something?
  3. Have you been drinking enough water?
  4. You’ve got another headache?
  5. Again?
  6. I get bad headaches too.
  7. It’s just a headache.
  8. I have some Tylenol if you want it.
  9. Just push through it!
  10. I think you just want an excuse.

Chances are, you’ve heard one or more of these pieces of “advice” at some point in your life. One comment in particular—“It’s just a headache”—encapsulates the popular misconception about a disorder that affects around 40 million Americans. It’s frustrating to feel that no one understands what you’re going through, and some, out of their own lack of knowledge, may even think you’re faking symptoms.

In order to demystify the stigma surrounding migraine disease, here are a few steps you can take to educate those around you about this debilitating neurological disorder.

Explain the Migraine Triggers

While migraine triggers differ from person to person, there are a few common causes that will bring about symptoms in many sufferers. For example, a naturally-occurring compound called Tyramine—often found in aged, smoked or cured meats and vegetables—has been found to be a major trigger of migraine attacks. If friends, family and coworkers have a better understanding of your migraine triggers, they’re more likely to notice when you’re experiencing an attack and can respond accordingly.

Provide Migraine Resources

Of course, you don’t need to justify your condition to everyone with whom you interact, but migraine symptoms can cause a strain on certain close relationships. For example, a boss or supervisor doubting the severity of your condition may cause you additional stress, which can negatively impact work performance or compound the pain. Fortunately, the National Headache Foundation has an abundance of resources that help skeptics and allies alike get a better understanding of migraine and headache. Sharing these informative sources with those closest to you can help alleviate the burden of constantly explaining your condition.

Seek Migraine Treatment from a Headache Specialist

Understanding the specifics of your condition makes it far easier to explain them to others. Seek out a headache specialist to receive an appropriate diagnosis. The health care practitioner will likely diagnose you based on your medical history, symptoms and a physical and neurological examination. This could include blood tests, magnetic resonance imaging (MRI) or computerized tomography (CT) scan. (It is critical to visit a medical professional who specializes in headache and migraine, as they will be able to best diagnose and treat the pain.)

There will always be those who doubt the severity of migraine symptoms. However, by educating yourself and those around you, you can help tear down the stigma associated with migraine disease and, in the process, make living with migraine attacks a bit easier.

Read this article online at Real World Health Care.

The Many Moods of Heart Failure and the Caregiver Challenge

Real World Health Care_____________________________________________________________________

Ann Laramee, APRN

Caregivers play an important role in the well-being of chronic heart failure patients. In addition to helping their loved one manage the physical and medical aspects of heart failure, they are called on to help with the patient’s emotional health.

According to Ann Laramee, APRN, Cardiology Nurse Practitioner in Cardiology and Palliative Medicine at the University of Vermont Medical Center, the heart is very sensitive to mood stressors like anxiety, fear, loneliness, anger and depression. She says that mood changes in heart failure patients can result in reduced compliance with treatment plans, longer recovery times and an increased risk of additional cardiac events.

Caregiving: A Burden or a Blessing?

Studies have shown that improved social support has been associated with better outcomes for patients living with heart failure. But often, caregivers themselves suffer from physical and emotional symptoms, according to Laramee, who notes that most caregivers of heart failure patients serve in that role for an average of 50 hours a week over 53 months.

“At the same time, caregiving can be very gratifying,” she says. “People say it brings fulfillment and meaning to their life. They feel appreciated.”

She encourages caregivers to take care of themselves so that they can be there for their loved one. She recommends many of the same self-care tips as she does to patients, including getting enough sleep, exercising regularly, eating a well-balanced diet and asking for support when needed.

Webinar for Caregivers

Additional insights from Laramee are available in a free webinar “Moods in HF and Caregiver Challenges” from the Heart Failure Society of America that’s perfect for caregivers, patients and families alike.

In the webinar, Laramee reviews the various moods that may affect a heart failure patient, how to recognize mood changes, when to seek help and the treatment options available. She also addresses the important role a caregiver plays, the challenges and rewards of caregiving, the importance of self-care and finding support when needed.

The HFSA Patient Education Webinar Series is provided to patients, caregivers and families through a collaboration between the Heart Failure Society of America and Mended Hearts. The series covers topics including heart failure diagnosis, therapies, clinical trials and diet and therapy advice. For more information, please visit www.hfsa.org/patient/webinarseries.

Read this article online at Real World Health Care.

How To Support a Friend with Heart Disease

Real World Health Care_____________________________________________________________________

Editor’s Note: When a family member or friend is sick with a chronic disease like heart failure, the role of caregiver often falls to women. However, more than one in three women is living with some form of cardiovascular disease themselves: It is the number one killer of women in the U.S. 

Go Red For Women is a global community whose hearts are united against heart disease. The following article is reprinted with their permission. Learn more about heart disease in women. Read the original article here.

You want to support a friend with heart disease or be part of a support system. Your support can help her feel better about her diagnosis and can even help her make healthier life choices.

Listen

When discussing her heart diagnosis with you, one of the best things you can do is listen. While it may be tempting to tell her all the ways she can eat healthier or exercise more often, focus instead on hearing her concerns before rushing to give advice.

“Just listening is a really easy way to show someone you care,” says Carol D’Anca, a Chicago-based clinical nutritionist and owner of Foods Not Meds, who has helped to support several women friends struggling with heart disease.

Get Informed

Chances are, your friend is going to the doctor quite a bit these days and may feel overwhelmed by the barrage of information given to her. Lighten her load by doing some research yourself, suggests D’Anca.

“Go online and help her with research about her condition and treatment options,” she says. “Work together to dig deeper and gain an understanding of what she is going through. Your willingness to help will go a long way.”

Socialize

Depression is an unfortunate byproduct of heart disease for many women. Upon receiving bad health news, they tend to shut themselves off from activities they once enjoyed. If this describes your friend, set up a regular social outing for the two of you (or invite others) – maybe a Tuesday afternoon tea hour or a movie night once a week.

“She will start to feel better emotionally when she feels love from others,” D’Anca says. “I also recommend helping them find a support group of others who are going through the same thing. Several of my friends have done this and it has brightened their moods tremendously, just knowing that they aren’t suffering alone.”

Get Active

Help improve your friend’s heart health by scheduling time to do activities together. Based on her likes and capabilities, organize a regular walk around the neighborhood or take a dance or step aerobics class together. Not only will the physical activity help your friend’s heart health, but it will improve her mood too.

Read this article online at Real World Health Care.