Five Things to Know: The Blood-Brain Barrier, Intestinal Permeability and Autism

In this new series, we’ll provide you with five things you need to know about breaking research at Massachusetts General Hospital.

Researchers from the Center for Celiac Research and Treatment at Massachusetts General Hospital and the Mucosal Immunology and Biology Research Center at MassGeneral Hospital for Children (MGHfC) recently came out with a study published in Molecular Autism. Here are five things to know:

  1. Autism spectrum disorder (ASD) is the fastest-growing developmental disability in the U.S., with 1 in every 68 children born in this country diagnosed with ASD. Parents and researchers alike are looking for both the causes and treatment options for this complex condition.
  2. The blood-brain barrier prevents materials in the blood from entering the brain, and intestinal epithelial tissue (the intestine’s lining) creates a boundary between the intestine and its external environment. When either of these two barriers isn’t functioning properly, it can lead to inflammation in the body.
  3. Researchers from the Center for Celiac Research and Treatment at Mass General and the Mucosal Immunology and Biology Research Center at MGHfC looked at how the blood-brain barrier and increased intestinal permeability, otherwise known as a ‘leaky gut’, might affect the development of ASD. The study involved analyzing postmortem brain tissues from 33 individuals (8 with ASD, 10 with schizophrenia and 15 healthy controls) and intestinal tissues from 21 individuals (12 with ASD and 9 without such disorders).
  4. The results showed alterations in both blood-brain barrier and intestinal permeability in individuals with ASD. This is the first time anyone has shown that an altered blood-brain barrier and impaired intestinal barrier might both play a role in inflammation of the nervous tissue in people with ASD.
  5. What’s next? Researchers plan to look at how microbiota, the collection of microorganisms in the gut, are linked with leaky gut and behavior. Researchers already know that kids with ASD have an altered composition of gut microbial communities. If they can figure out what is required or missing, then they can come up with a treatment that might be able to improve some of the behavioral issues and/or the gastrointestinal symptoms.

Learn more about this study here.


Hormone May Protect and Preserve Ovaries During Chemotherapy

Chemotherapy’s anti-cancer effects depend on its ability to damage rapidly growing cells, which is beneficial when targeting cancer cells that multiply rapidly. However, chemotherapy also causes collateral damage to other types of rapidly growing cells, including cells found in the ovaries. A naturally occurring hormone that plays an important role in fetal development, called Mullerian Inhibiting Substance (MIS), may be effective in not only preventing pregnancy during chemotherapy (which is not recommended because of the potential for drugs to harm the developing baby), but also can protect immature egg cells and potentially reduce the risk of infertility down the line.

A team from the Pediatric Surgical Research Laboratories in the Massachusetts General Hospital Department of Surgery found that boosting MIS levels can pause the early development of ovarian follicles when egg cells are maturing, thus protecting them from chemotherapy-induced damage. When MIS levels were increased in a series of experiments with female mice, researchers saw a significant decrease in the number of growing follicles. After several weeks, there was an almost complete lack of growing follicles. When the treatment stopped, the follicle development process resumed, showing that the effect is reversible.

These findings were unexpected for researchers, who were previously unaware of MIS’ ability to block the entire follicular development process. The results also provide new hope for preserving fertility in women undergoing chemotherapy. In addition to damaging cells found in the ovaries, chemotherapy speeds up natural ovulation processes, essentially using up the reserve of immature eggs in a matter of months rather than years. The ability to potentially maintain the larger pool of eggs not only could maintain fertility during chemotherapy but also could be applied to modern fertility treatments and contraceptives.

Researchers have just started to scratch the surface of the implications of MIS for reproductive and overall health. MIS could potentially prove useful in treating many conditions that cause ovarian insufficiency or premature menopause.

Motohiro Kano, MD, of the Massachusetts General Hospital Department of Surgery, is lead author of this study. Patricia K. Donahoe, MD and David Pepin, MD, are corresponding authors.

You can find the full press release here and the original paper here.

Study Provides New Treatment Option For Recurring Prostate Cancer Patients

There is new hope for the more than 30 percent of prostate cancer patients who will experience cancer recurrence after undergoing surgery to remove their prostate gland.

Prostate cancer cells need androgens (also known as male hormones) to grow, and, in order to function properly, androgens must bind to receptors in the prostate. Medications called antiandrogens can bind to these receptors to block the androgens. A new study from the Mass General Department of Radiation Oncology found that adding antiandrogen drugs to standard radiation therapy can improve the survival of patients facing post-surgery prostate cancer recurrence. Investigators believe that their findings will change the standard of care and provide new treatment options for patients experiencing a postoperative recurrence.

The clinical trial looked at 760 prostate cancer patients who had recurrent cancer after surgical removal of the prostate gland. Participants were randomly assigned to either receive an antiandrogen drug (bicalutamide) or a placebo for 24 months in addition to six and a half weeks of radiation therapy.

The long-term study found that adding antiandrogen drug therapy to radiation treatment reduced the death rate in a subset of prostate cancer patients by more than half. The group who received the combination treatment as part of the clinical trial were also 50 percent less likely to develop cancer in another area of the body. The treatment also didn’t seem to have negative side effects on the heart and liver.

Research is currently underway to test the effectiveness of newer antiandrogen drugs. Those trials started about five years ago so it will take some time to get their results.

William U. Shipley, MD, of the Massachusetts General Hospital (MGH) Department of Radiation Oncology, is lead author of this study.

Interested in learning more? See the full press release here, and read the original study here.