Investigators Add New Insights to Lyme Disease Diagnosis and Treatment

tick.jpgWith the number of reported Lyme disease infections expected to reach record highs in 2017, Massachusetts General Hospital researchers are helping to meet the need for new diagnostic tools and treatments.

The work of John Branda, MD, and Allen Steele, MD, was recently featured on the Mass General Giving Website. Here is a brief summary of the article, which you can find in full here.

A New Test for Lyme Disease

Lyme disease is caused by the bacterium Borrelia burgdorferi (B. burgdorferi), which is transmitted to humans through the bite of an infected blacklegged tick, commonly known as a deer tick. The tick must be attached for 36 to 48 hours or more before the Lyme disease bacterium can be transmitted.

As with many infectious diseases, early detection plays a key role in treatment. John Branda, MD, associate director of the Clinical Microbiology Laboratory at Mass General, and his colleagues are developing a new way to diagnose Lyme disease, as current blood tests frequently yield false negative results in the weeks after infection.

The team’s new testing technique starts with a blood sample that is first amplified by polymerase chain reaction technology, a method that can make the genetic material of a pathogen such as B. burgdorferi more easily identifiable.

Then the blood is then scanned with magnetic resonance imaging, which can quickly pick up the Borrelia DNA. The test, known as T2MR, was able to detect B. burgdorferi in blood samples from patients who were suspected of having Lyme disease but had tested negative using traditional techniques.

Genetic Factors

In a separate research study, Allen Steere, MD, a Mass General rheumatologist and the researcher who led the team that first identified Lyme disease in the 1970s, is exploring why some patients do not recover from the disease even after receiving a course of antibiotics.

While the antibiotics are able to clear the infection, some patients still experience pain, fatigue and neurocognitive symptoms. A few patients can go on to suffer from antibiotic-refractory Lyme arthritis — a painful inflammation of the joints that long outlasts the infection.

In these patients, there is mounting evidence that Lyme disease triggers an abnormal immune response, which in turn attacks the tissues of the joints, even after B. burgdorferi has been cleared by antibiotics.

Dr. Steere believes that many more severe cases may result when people with a specific genetic profile encounter a particularly virulent strain of the bacterium.

When genetic susceptibility and virulent B. burgdorferi strains combine, as they do in as many as 20% of people of Caucasian ancestry who are infected with Lyme disease, ideal conditions are created for an amplified and maladaptive inflammatory response that can attack joint tissues.

To learn more about the symptoms and causes of Lyme disease, and for tips on protecting yourself from tick bites, please visit the Centers for Disease Control’s Lyme disease website.

A Snapshot of Science: A New Approach to Targeted Cancer Treatments, Identifying Genes that Help Protect the Gut and Much More!

We wanted to share some recent Massachusetts General Hospital research that has been published in high impact, top-tier journals. This is just a small snapshot of the incredible research that takes place at Mass General each day — there’s lots more to find on the Mass General website!


Cognitive Decline, Tau and β-Amyloid in Healthy Older Adults
(Summary submitted by Rachel Buckley, PhD, and Rebecca Amariglio, PhD, both of the Martinos Center for Biomedical Imaging)

We published findings from the Harvard Aging Brain Study (Department of Neurology, Massachusetts General Hospital) investigating the link between subjective memory complaints (when a patient reports a worsening of their thinking abilities, including memory) and Alzheimer’s disease pathology in individuals who are otherwise cognitively normal. We found that increasing memory complaints were linked with greater amounts of tau in the brain, a naturally occurring protein that is associated with neuron loss in Alzheimer’s disease. We posit that memory complaints are a very early marker of disease, as they relate to tau build up before clinical tests can detect memory impairment.

Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden
Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, [et al.] Amariglio RE
Published in JAMA Neurology on October 2, 2017


New Approach to Targeted Cancer Treatment 
(Summary submitted by Conor L. Evans, PhD, of the Wellman Center for Photomedicine)

We have created a promising new light-activated, cancer-targeting therapeutic. Cancer drugs often cannot reach every cell in a tumor, leaving behind cells that can become resistant to treatment. At the same time, these drugs can cause unwanted systemic problems, such as weight and hair loss, elsewhere in the patient’s body. Our therapeutic was built to diffuse throughout tumors, target cancer cells, and kill these cells only when activated by light to avoid unwanted and burdensome side effects. We hope that this approach could one day find use in the fight against treatment-resistant cancers, like breast and lung.

An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy
Klein OJ, Yuan H, Nowell NH, Kaittanis C, Josephson L, Evans CL
Published in Scientific Reports on October 17, 2017


Identifying Genes that Help Protect the Gut 
(Summary submitted by Javier Elbio Irazoqui, PhD, formerly of the Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease)

The intestinal epithelium is a single layer of cells that protects the gut from environmental insult. Defects in this layer are linked to many diseases, including inflammatory bowel disease. Despite its critical importance, very little is known about the genes in the epithelium involved in this function. We found that transcription factor TFEB, a master regulator of lysosomal gene expression, provides a protective effect, and this function is mediated by expression of apolipoprotein A1, the major constituent of HDL, aka “good” cholesterol. Our findings suggest that enhancement of TFEB activity in the intestinal epithelium could be a therapeutic approach to enhance Apolipoprotein A1 expression for the treatment of inflammatory bowel disease.

Transcription Factor TFEB Cell-Autonomously Modulates Susceptibility to Intestinal Epithelial Cell Injury In Vivo
Murano T, Najibi M, Paulus GLC, Adiliaghdam F, Valencia-Guerrero A, Selig M, [et al.] Xavier RJ, Lassen KG, Irazoqui JE
Published in Scientific Reports on October 24, 2017


Patient Resistance to Immune Checkpoint Blockade Therapies
(Summary submitted by Nir Hacohen, PhD, of the Cancer Center)

Cancer therapy has been transformed in the last few years by immune-based therapies, called ‘checkpoint blockade’ therapies. An important question is why some people respond and others do not respond to this therapy. By analyzing the DNA of tumors from patients who developed resistance to checkpoint therapy, we found changes in the DNA of a key gene that is critical for tumors to be detected by the immune system. In this way, the tumor has learned how to hide from the immunotherapy. Knowing this will help us decide which patients would benefit from immune therapy. Finding ways to make these resistant tumors visible to the immune system is an important goal for the coming years.

Resistance to Checkpoint Blockade Therapy Through Inactivation of Antigen Presentation
Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, [et al.] Flaherty KT, Sullivan RJ, Hacohen N
Published in Nature Communications on October 26, 2017

World Diabetes Day 2017

tumblr_inline_ofnq35sy4J1tq32mi_540.jpgDiabetes impacts an estimated 425 million people around the world, and that number is projected to rise to 693 million by 2045, according to the annual diabetes atlas released today by the International Diabetes Federation (IDF).

Diabetes develops as a result of having too much sugar in the blood. Over time, that imbalance can cause serious and costly health problems including heart disease, stroke, kidney disease and eye problems. The IDF diabetes atlas estimates that the world spends more than $720 billion on health care expenditures related to the disease.

November 14 marks World Diabetes Day – a day to raise awareness of the growing diabetes epidemic and the need for a cure as well as improved prevention and treatment methods.

Here are just a few examples of how Massachusetts General Hospital researchers are working to advance diabetes research and care:

  • Investigators have reason to believe that a vaccine originally used to treat tuberculosis could provide new hope for patients with type 1 diabetes.
  • People with type 2 diabetes are particularly prone to ulcers on the bottom of the foot, which can increase the risk of death and often result in a major amputation. Ulcers take months to heal, but a new discovery about mature B lymphocytes – best known for producing antibodies – could hasten wound recovery.
  • Researchers have developed a new method for measuring blood sugar levels in diabetes patients that could reduce testing errors by 50 percent.
  • Treatment guidelines for patients with type 1 diabetes have long called for yearly eye exams. But is there an alternative to this one-size-fits-all approach that could reduce patient burden and costs while providing a quicker diagnosis? Findings from a recent study lend insight into a possible new eye screening protocol.
  • Check out the Mass General Diabetes Unit, which seeks to advance the care of people with diabetes nearby and worldwide. U.S. News & World Report ranks Mass General Diabetes & Endocrinology among the best in the nation.

 

Weekend Links

Placebo.png

We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Rebranding placebos: Harnessing the power of sham therapies for real healing might require a new lexicon

Researchers produce the first draft cell atlas of the small intestine

‘Extraordinary’ tale: Stem cells heal a young boy’s lethal skin disease

Decisions, Decisions: The Neuroscience of How We Choose (Science Weekly podcast)

Are you preparing a research poster?
A Quick Poster Checklist (From the University of Washington)
University of Texas Poster Review

Top photo courtesy of Knowable Magazine (CREDIT: TEXTBOOK EXAMPLE [CC BY-ND])

Researchers Use Machine Learning to Improve Breast Cancer Screening Techniques

Imagine enduring a painful, expensive and scar-inducing surgery—only to find out afterwards that it wasn’t necessary.

This is the situation for many women with high-risk breast lesions—areas of tissue that appear suspicious on a mammogram and have abnormal but not cancerous cells when tested by needle biopsy. Following surgical removal, 90% of these lesions end up being benign.

A change in the standard of care could be on the horizon thanks to researchers at Massachusetts General Hospital and MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) who have found a more precise and less invasive way to separate harmful lesions from benign ones.

MIT-AI-Cancer-Detection-01_0.jpg
From left: Manisha Bahl, director of the Massachusetts General Hospital Breast Imaging Fellowship Program; MIT Professor Regina Barzilay; and Constance Lehman, chief of the Breast Imaging Division at MGH’s Department of Radiology. Photo courtesy of MIT News

“The decision about whether or not to proceed to surgery is challenging, and the tendency is to aggressively treat these lesions [and remove them],” said Manisha Bahl, MD, Director of the Breast Imaging Fellowship Program at Mass General, in a recent interview.

Bahl, along with a team of researchers, have harnessed the power of artificial intelligence (AI) to develop a more accurate and less invasive screening method for high-risk lesions. When tested, the machine correctly diagnosed 97 percent of 335 high-risk breast lesions as malignant and reduced the number of benign surgeries by more than 30 percent compared to existing approaches. These results were recently published in Radiology.

The team developed an AI system that uses machine learning to distinguish between high-risk lesions that need to be surgically removed from those that should just be watched over time. They created this model by feeding it data on over 600 high-risk lesions, including information on the patient’s demographics and pathology reports, and then tasked it to identify patterns among the different data elements.

Through a process called deep learning, the machine uses the data to create an algorithm that can be used to predict which high-risk lesions should be surgically removed. This process differs from traditional software programming in that the researchers did not give the machine the formula for diagnosis, but rather let it analyze the data and identify patterns on its own.

“To our knowledge, this is the first study to apply machine learning to the task of distinguishing high-risk lesions that need surgery from those that don’t,” said collaborator Constance Lehman, MD, PhD, chief of the Breast Imaging Division at Mass General’s Department of Radiology, in a recent interview. “We believe this could support women to make more informed decisions about their treatment and that we could provide more targeted approaches to health care in general.”

Lehman says Mass General radiologists will begin incorporating the model into their clinical practice over the next year.

Pocket-Sized Device Provides Food Allergy Sufferers with Life-Saving Tableside Lab Results

If you’re among the 50 million Americans with a severe allergy to foods like gluten or nuts, every meal at a restaurant can feel like a potential land mine. Even if the restaurant has made an effort to provide dishes that are allergen-free, worries of cross-contamination and a subsequent severe or potentially life threatening reaction can still put a damper on your dinner plans.

To help ease concerns and keep food allergy sufferers safe, a team at Massachusetts General Hospital has developed a new device small enough to fit on a keyring that costs only $40 and can quickly and accurately test for food allergens.

While advances have been made in the packaged food industry, where new federal regulations require the manufacturer to disclose whether the product is made in a facility that also processes common allergens, these disclosures are not always accurate and there are no similar regulations for the restaurant industry.

Rather than force diners to completely avoid foods that have the chance of containing an allergen, or eat something only to regret it later, Mass General researchers created integrated exogenous antigen testing (iEAT), a pocket-sized device that can accurately analyze food for the presences of allergens in less than 10 minutes. Specifically, the device can screen for peanuts, hazelnuts, wheat, milk and eggs.

keychain pic.jpeg
The iEAT system

Developed by co-senior team leaders Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology (CSB) at Mass General and Hakho Lee, PhD, Hostetter MGH Research Scholar and Director of the Biomedical Engineering Program at the CSB, the device consists of three components:

  1. A small plastic test tube that the user can put a small sample of food into. The tube contains a solution that dissolves the sample and adds magnetic beads to the solution. The beads are designed to bind to the food allergen of interest.
  2. The user can then drop the solution onto an electrode chip, which is inserted into the keychain sized reader.
  3. The reader analyzes the sample and indicates on a small display whether the allergen is present, and if so, in what concentration.

Testing performed by the research team showed that measurements of the concentration of the allergen is extremely accurate. In fact, the device could detect levels of gluten that were 200 times lower than the federal standard. Accuracy is key because everyone’s sensitivity varies — some individuals could experience a reaction after consuming a miniscule trace of an allergen.

Weissleder and Lee have also developed a smartphone app to complement iEAT. With the app, users can compile and store the data they collect as they test different foods for various allergens at different restaurants and even in packaged foods. The app is set up to share this information online so others with the app will be able to find restaurants with foods that consistently have no or low levels that are below the individual’s triggering concentration.

cell phone app

Consumers may be able to purchase the $40 iEAT device and corresponding app in the near future — the research team has granted a license to a local start-up company to make the system commercially available. Weissleder and Lee also report that they could apply this technology to detect other substances in food such as MSG or even pesticides.

This research was recently highlighted in an NIH article and published in ACS Nano.

It was also recently featured in a news story on CBS Boston.

Weekend Links

MIT.png

We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Creative Minds: A New Way to Look at Cancer

Better Patient-Provider Communication Needed for Obesity Care

Eugenics 2.0: We’re at the Dawn of Choosing Embryos by Health, Height, and More

6 Speaking Tips for Scientists and Engineers (editor’s note: Melissa Marshall, featured in this article, recently spoke to Mass General clinicians about how to effectively present scientific work. We were so impressed by her talk that we wanted to introduce her to our readers) 

Looking for a great book for the young scientist in your life? The long list of 2018 AAAS/Subaru SB&F (Science Books and Films) Prize winners for Excellence in Science Books has been released. Prizes are awarded each year in the following categories:

  • Children’s Science Picture Books
  • Middle Grade Science Books
  • Young Adult Science Books
  • Hands on Science Books

See the full list here

 

Top photo: courtesy of Tim Lahan, MIT Technology Review