Chronic Disease

Having a relative with type-1 diabetes makes you 15 times as likely as other people to get the disease, in which the body inappropriately destroys insulin-producing cells in the pancreas. But unlike the more common form of diabetes, type-2 diabetes, physicians don’t know how to prevent type 1 diabetes from developing in at-risk individuals.

To find out, they’re studying family members of type-1 diabetes patients. The large, multi-center research effort, called Type-1 Diabetes TrialNet, screens these folks for the presence of antibodies that recognize “self” tissues and could act as markers of diabetes vulnerability, and invites individuals who have the autoantibodies to take part in diabetes-prevention research. Stanford and Lucile Packard Children’s Hospital are among the 18 clinical centers participating in TrialNet research.

The big news at TrialNet is that, starting today, the first part of the screening process is moving online. Volunteers used to have to participate in a screening event or come to a trial center to be screened, but many people live far from these centers. At the TrialNet screening website, people can now answer a short set of questions to find out if they’re eligible for TrialNet’s research and give consent to participate in screening. After the online questions are complete, eligible volunteers will receive a kit in the mail that they can take to a local lab for a free screening blood test.

Researchers hope this online process will make it easier for more people to participate in type 1 diabetes research. TrialNet must screen more than 20,000 relatives of people with type 1 diabetes each year to reach its scientific goals, according to an National Institutes of Health press release about the new online screening.

Previously: Beta cell development explored by Stanford researchers, Researchers struggle to explain rise of Type 1 diabetes and A patient perspective on social media

When I recently learned that my cholesterol was a bit high, I was told that a regular exercise routine and a couple of oatmeal breakfasts per week should do the trick to bring the numbers back to a normal range. But for Brenda Gundell, a genetic disease called Familial Hypercholesterolemia, or FH, means that simple lifestyle changes won’t make for a quick fix.

FH affects cholesterol processing from birth, and while the condition is common - affecting more than 600,000 people in the U.S. - it is diagnosed in less than 10 percent of those who have it. Gundell was only 15 when she first heard about FH; her father, just 39 at the time, had such extreme levels of total cholesterol that they led to a fatal heart attack. Fortunately for Gundell, while the disease can be destructive, it is, in fact, treatable. And, with the help of FH specialists at Stanford’s Preventive Cardiology Clinic, Gundell has kept her cholesterol in check for the last 17 years and is looking forward to a long life.

Grundell’s story is detailed in the Stanford Hospital video above.

So-called Lewy bodies - gumball-like clumps rich in a mystery molecule called alpha-synuclein - abound in Parkinson patients’ brains and are considered the hallmark of the disease. Up to now, researchers have had few solid clues as to what this “black hat” protein is doing in the brain in the first place.

But a team led by Stanford neuroscientists Tom Sudhof, MD, and Axel Brunger, PhD, has revealed a likely critical role played by alpha-synuclein in healthy brains. Their discovery is described in an article just published in the open-access online journal eLife.

Each of the human brain’s roughly 200 billion nerve cells communicates directly with, on average, 10,000 others by squirting signaling chemicals called neurotransmitters at them. It is all this squirting that underpins our thoughts, feelings and movements.

Of course, the brain’s activity is no mob squirt-gun shootout. Consider: The 2 quadrillion separate nerve-cell connections in your brain or mine roughly equal the number of stars in 7,000 Milky Way galaxies. For our most exalted organ to do its job, the signals that nerve cells send must be marked by profound precision, both in their intensity and in their timing.

As I wrote in my release accompanying the eLife article:

Nerve cells don’t simply squirt out neurotransmitters willy-nilly. Within the complex networks that constitute our brains, every individual nerve cell has a lengthy, snaking, tubular extension cord, or axon, that hooks up with thousands of other nerve cells. Neurotransmitters are housed within tiny bubble-like packets in the cell. These packets congregate in myriad small, bulbous nozzles dotting the axon, with each bulb abutting a downstream nerve cell. When an electrical impulse travels down the axon on which those bulbs reside, it triggers the fusion of the neurotransmitter-packed packets with the nerve cell’s outer membrane. The packets’ contents then spill into the narrow space separating the bulbs from the nerve cells they abut.

The Sudhof-and-Brunger team was able to show that alpha-synuclein helps regulate the orderly clustering of the neurotransmitter-loaded packets near their release sites. Alpha-synuclein has to be present in the right amounts, though; too much or too little has untoward consequences - which could explain why previous research has yielded conflicting results.

It’s nice to know, before messing around with it in living people, that in the healthy brain alpha-synuclein is a lot more than just a raw material in a gumball factory. Drug companies may have perhaps been led down some blind alleys as a result of locking in, too early, on the notion that yet another clump-generating protein, A-beta, was the Bad Guy in Alzheimer’s disease and that, it followed, getting rid of it would be a good idea. Maybe not so fast…

Previously: Nervous breakdown: Preventing demolition of faulty proteins counters neurodegeneration in lab mice, Stanford scientist sets sail on new publishing model with launch of open-access, embargo-free journal and Stanford study identifies molecular mechanism that triggers Parkinson’s
Photo by akeg

My now-husband and I were together when I learned I had a chronic illness - a rare blood disorder - 13 years ago. (I’ll never forget how hard he held my hand as we sat in the waiting room before my bone marrow aspiration, or how he went out and bought me a pair of flannel pajama bottoms to lounge around in on those days when I was waiting for the results and feeling weepy and scared.) I never had to deal with telling a potential mate that I had a disease, but I can’t imagine it would be easy. Which is why I found this first-person piece on the The Global Gene Projects’ website of interest. There, a guest blogger shares her own experience and offers advice from an expert:

One of the biggest questions in regard to this topic, at least for me, was how long into the relationship should a rare disease patient approach the topic of disease and diagnosis? (I had a feeling that [the therapist's] answer wouldn’t be “well just ambush them with it on the first date and see how it goes.”)

Instead [Dawn Wiggins, a licensed family and marriage therapist] replied, “When to discuss your health diagnosis and related issues with someone you are dating depends on what the expectations are for the relationship. If it is a casual dating relationship there is less burden or urgency to disclose early in the relationship. If there is a risk that your disease and symptoms could impact the time you are spending together, you may need to disclose. If your relationship is more serious and there is an expectation of a longer term commitment, it is important to be honest sooner than later.”

Previously: Broken: A poem about coming to grips with chronic disease

A luminescent lab mouse, genetically engineered to produce the same protein that makes fireflies’ tails light up, may accelerate progress in coming up with treatments for muscular dystrophy. This bioengineered mouse also has a genetic defect that, like its counterpart gene defect in people, causes the disease.

The luminescence happens only in damaged muscle tissue, and its intensity is in direct proportion to the amount of damage sustained in that tissue. So each glowing mouse muscle gives researchers an accurate real-time readout of just how much the disease has progressed and where.

It adds up to vastly expedited drug research. Tom Rando, MD, PhD, director of Stanford’s Glenn Laboratories for the Biology of Aging and founding director of Stanford’s Muscular Dystrophy Association Clinic, told me. As I wrote in my release about his new report in the Journal of Clinical Investigation about the Rando lab’s invention:

No truly effective treatments for muscular dystrophy exist. “Drug therapies now available for muscular dystrophy can reduce symptoms a bit, but do nothing to prevent or slow disease progression,” said Rando. Testing a drug’s ability to slow or arrest muscular dystrophy in one of the existing mouse models means sacrificing a few of them every couple of weeks and conducting labor-intensive, time-consuming microscopic and biochemical examinations of muscle-tissue samples taken from them, he said.

With an eye to vastly speeding up drug testing while simultaneously dropping its cost, Rando and his colleagues developed the new experimental strain whose glow (you see it through the skin) gives investigators an instantaneous, accurate reflection of what’s going on inside a mouse’s muscles, well before the degenerative changes could have been observed using standard detection techniques - without any need to kill the mouse in order to get the results.

Trivia point: The word “muscle” comes from the Latin musculus, meaning “little mouse.” More than mere coincidence?

Okay, probably not. But I thought it was worth mentioning.

Previously: Aging research comes of age, Can we reset the aging clock, one cell at a time? and Mouse model of muscular dystrophy points finger at stem cells
Photo by Goldring

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; the latest comes from Iowan Dawn M. Nellor.

Imagine you’re a busy specialist, preparing to meet a new patient in your office…

You note that your patient only slightly smiles and seems a bit distant. Many of your patients come in with three backpacks full of medical records, yet she has nothing. If this patient is so ill, where are all her labs and tests? You note that she’s watching your every move, and you can’t help notice that she’s mainly watching your face. Where is her laundry list of symptoms and complaints, you wonder. You ask her what’s going on and what brings her in today. In a quiet voice she answers, “I’ve had pulmonary sarcoidosis for four years, and I’ve been having facial and hand pain for two years, and no one knows what’s wrong.” You’re puzzled by her, wondering why she’s monotone and aloof. Do you ask yourself, “Is that it, just one sentence from a chronically ill patient?” And do you feel concerned - or lucky?

As a person with a so-called invisible illness, my behavior at my last appointment with a specialist mimicked that of the patient in the scenario above. Why did I act this way? Because I was afraid to be there, and because I had low expectations for the visit. The behavior of past appointments with family practice physicians and specialists have numbed me to their raised eyebrows and the “look-away” that represents disbelief. I already know when the arms are crossed and the chair rolls back that the doctor’s next questions will be, “Are you sure it’s not stress? Do you exercise? Are you on antidepressants? Why don’t you see your psychiatrist, or try a different medication?”

There’s a major communication gap between chronically ill patients and some physicians. I don’t criticize every doctor by any means. But I feel that not enough physicians understand that both doctors and patients want and deserve respect, and to be heard. Patients don’t want to feel dismissed.

Based on my experience of not always having been heard, I’ve made changes in my life to empower myself. I live in a small community, but through online support groups I constantly talk with others affected by rare diseases to raise awareness on what life is like living with one or having a love one affected by one. I attend cognitive therapy weekly to take more control over various areas of my life and to be reminded that I still need to ask for help. I’ll soon be going to a pain management clinic that has an intense program in which a psychologist helps with coping skills related to the pain and a physical therapist works with you. I educate myself more through reputable medical sites, and I keep my primary care physician educated on clinical news.

As for changes physicians might consider, one way to improve physician/patient communication is for doctors to read and understand first-hand patient accounts - and to understand that if a patient isn’t saying much during an appointment, there’s probably a good reason. And I encourage physicians to be more aware of their body language when talking with patients, particularly those struggling to get the right diagnosis. If we sense that you’re frustrated even before you say hello, we’ll likely close up and just go through the motions during our appointment - like the patient did above. And how unfortunate would it be if you were the one doctor who could actually help that patient?

Dawn M. Nellor, of Audubon, Iowa, advocates for rare diseases and education on the stigma of invisible illnesses. She’s currently learning lobbying at the legislative level for sarcoidosis research and treatment. Her greatest joys in life are music and her pets, which include one Maltese dog and four cats.

For young patients coming into the hospital several times a week for dialysis, balancing school work and the long hours spent getting treatment can be a challenge. So Lucile Packard Children’s Hospital hired a teacher to work exclusively with hemodialysis patients and help keep them up to date with classwork.

A recent Packard Children’s article offers a closer look at the program and instructor Katie Fennimore, a former elementary school teacher trained to work with children with special needs. To help kids make the most of their time, Fennimore uses a variety of tactics, including declaring the first hour of treatment a no-TV “power hour” and loading educational materials and apps onto iPads and computers at the dialysis center. Beyond keeping students focused on academics, she also helps make sure parents, school teachers, administrators, doctors and nurses are updated on patients’ medical status and needs. From the piece:

Lori Vargas is mother to 15-year-old dialysis patient Taylor Simpson, who was diagnosed with Goodpasture syndrome just over a year ago. Vargas said, “Katie is a huge help for us. She helps bridge the communication between us and the school when we need that extra support.”

In Fennimore’s role, knowing her dialysis students individually is key to helping their progress. Vargas added, “Katie knows, off the top of her head, everything that is currently going on in Taylor’s classes. She will also be attending Taylor’s [Individualized Education Plan] meeting via conference call to help us communicate with Taylor’s teachers and explain the importance of Taylor staying in school even though she has this illness.

…

“Katie is a great motivator for Taylor while she’s here in dialysis to stay focused on her homework and grades,” said Vargas. “She rocks! We are grateful for all her help.”

Photo by Lucile Packard Children’s Hospital

It’s been just over a year since we began our collaboration with Inspire, a company that builds and manages online support communities for patients and caregivers. Each month, an Inspire-identified patient shares his or her own unique experience living with a rare or chronic illness, and a reoccuring theme has been the patients’ desire to to be considered by their physicians a true partner in the care process.

Our friends at Inspire have now compiled a year’s worth of these columns in a report (link to .pdf) called “Experts by Experience.” It’s aptly titled, I believe, and I couldn’t agree more with Aanand D. Naik, MD, who wrote a forward to the report calling the writers “inspiring in their honesty, strength, struggle, and perseverance.”

Heart disease is the primary cause of death for the more than 20 million people in the United States with chronic kidney disease (CKD). For kidney patients who have secondary diagnoses of coronary artery disease or diabetes, which puts them at particularly high risk of heart attack or stroke, the cholesterol-lowering drugs statins are routinely prescribed.

But for the remainder of patients with chronic kidney disease, it’s unclear whether statin treatment is either cost effective or medically prudent. A Stanford study published today in the Journal of the American College of Cardiology sheds some light on the issue.

…At very low prices, generic statins are cost-effective in nearly all patients with chronic kidney disease

“We did a cost-effectiveness analysis weighing the potential benefits in patients with chronic kidney disease and hypertension,” first author Kevin Erickson, MD, a Stanford nephrologist, recently explained to me. “We essentially show that at very low prices, generic statins are cost-effective in nearly all patients with chronic kidney disease, but at average retail prices they are only cost-effective in patients with kidney disease who have higher cardiovascular risk.”

The study also indicates that adverse side effects of these drugs, including muscle-related toxicity, and potential diabetes and memory loss, should be taken into consideration by clinicians when determining treatment options. “While statins reduce absolute [cardiovascular disease] risk in patients with CKD, increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains,” Erickson and his co-authors cautioned in the paper.

Previously: Wider statin use may be cost-effective way to prevent heart attacks

The field of neurology - or neurobiology, or neuroscience, take your pick - is named in honor of a talented tenth of the cells in the human brain, which respectable scientists call neurons and the rest of us call nerve cells. The other nine-tenths consist of three distinct types of cells collectively lumped together under the term “glia,” after the Greek word for glue.

You can infer from that monicker that those “other” brain cells haven’t been held in overly high regard. As I once wrote in a Stanford Medicine article called “The Brain’s Silent Majority:”

Unlike their flashier electronic cousins [the neurons], glia speak in chemical whispers. Learning their language has been tougher. As a result, glial cells were long seen as inert nerve cement: just so many packing peanuts whose raison d’être is to keep our neurons from jiggling when we jog.

But pioneering Stanford gliologist (I just made up that term) Ben Barres, MD, PhD - who trained as a practicing neurologist before circling back for his PhD - couldn’t help noticing, in autopsies, that the brains of people with “neurological” disorders invariably showed obvious signs of glial disarray. So he resolved to devote his career to the study of glial cells, which have now emerged as major players in, among other things, the formation and pruning of the all-important neuron-to-neuron contacts called synapses.

In the strictly material sense, “you” aren’t much more or less than the sum total of all your synapses - about 100 trillion of them. That would (again, strictly materially speaking) elevate glia to a godlike status, wouldn’t it?

But on Earth, at least, power is a double-edged sword. Barres and others have amassed a growing pile of implications about the kinds of damage - from neurodegenerative disorders like Alzheimer’s to neurodevelopmental ones like autism and Rett syndrome - that can result when glia go wrong.

Barres and a postdoc in his lab, Steven Sloan, PhD, have penned a commmentary in a just-published issue of Proceedings of the National Academy of Sciences, to accompany a study by other researchers fingering glial-cell malfunction in yet another scourge: amyotrophic lateral sclerosis (ALS). The most frequent form of motor-neuron degenerative disease, ALS is informally known as Lou Gehrig’s disease in memory of a baseball star of yesteryear who, slowly and very publicly, died too young.

Write Barres and Sloan:

For many years, a neuron-centric mentality has dominated this field of research… But this strict attention on neuronal pathology is beginning to broaden… [The new study] shows that glial cells unexpectedly can play a much more fundamental, even primary, role in driving neurodegenerative disease.

Has brain science, unlike the proverbial drunk who kept on looking for his car keys under the lamppost not because he dropped them there but because the light is better, managed to stop looking for defects in all the wrong places?

Previously: Using video and a white board to describe complicated research, Neuroinflammation, microglia, and the brain in the balance, Unsung brain-cell population implicated in variety of autism and Surprise! Warrior immune proteins help heal injured nerves
Photo by CapitalK buy design