The beginning of it goes into a strange array of gene talk but then the focus of the article is this---
Some signals associated with a cell type called microglia were far higher in the samples from people with autism than from samples of people with other conditions. This signal may be higher because the microglia are more active. If that’s true, an antibiotic that reduces their activity could be one way to treat the condition—which is what UCLA Health psychiatrist and one of the authors of the study, Dr. Michael Gandal, is testing right now....
He and his colleagues are working to recruit about 30 adults for a brain-imaging study to look at their microglia and take an antibiotic called minocycline for 12 weeks.
“Throughout the 12 weeks, we measure a set of cognitive tasks, and we repeat the brain imaging," he said. "The idea is to look at how levels of inflammation in the brain relate to cognitive and behavioral function in individuals with autism.”
Autism spectrum disorders (ASD) are highly disabling, persistent neurodevelopmental disorders. There are no available treatments for core symptoms of ASD or biologically-based clinical biomarkers. Emerging evidence indicates that levels of brain inflammation are increased in ASD. In particular, recent work implicates hyperactivity of microglial cells, the resident immune cells of the brain. However, the functional consequences of microglial activation remain unknown. This study will measure microglial activation in ASD using positron emission tomography (PET) brain imaging. Adult males with ASD (n=15) and healthy controls (n=15) will be recruited for this study and undergo comprehensive clinical and behavioral baseline assessment. All subjects will then undergo baseline PET imaging using a radiotracer that labels activated microglia. Subjects with ASD will then undergo 12-week open label treatment with minocycline, an FDA-approved antibiotic thought to block microglial activation. PET imaging will be repeated at 12 weeks to confirm target engagement. A subset of control subjects will also undergo repeat PET imaging to determine test-retest reliability. During minocycline treatment, ASD subjects will be evaluated every 2 weeks for safety, clinical impression, behavioral functioning, and measures of cognition. Results will provide important information regarding the relationship between levels of brain inflammation, cognitive and behavioral function in ASD.
I am hoping that more candidates can join as it looks like almost a year since it's been updated. Let's take a look at Minocycline and see if we can't get more people excited and involved in this type of research.
It's been about six years since I really started putting a focus on autism and bacterial infections. Because I have a daughter who has a diagnosis of autism and also an autoimmune diagnosis, the immune system has become a key player in my research to help her. The MICROBIOME research has exploded and its connection to the MICROGLIA of the brain may be a big part in autism spectrum disorders.
There are far too many children and young adults who suffer. The list of painful and debilitating symptoms grows as parents watch in agony. Patterns tend to emerge:
CHRONIC VIRAL and BACTERIAL INFECTIONS
REGRESSION of SKILLS and LANGUAGE often with LOSS of SPEECH
PAINFUL GI DISEASES
ISSUES WITH EATING and FOOD
OCD, PERSEVERATION and TICS
CHRONIC DIARRHEA and/or CONSTIPATION
SELF-INJURIOUS HEAD BANGING
IRRITABILITY and AGGRESSION from PAIN
☤ Particular case studies also link antibiotic treatment to improvements in ASD behaviors and comorbid conditions (51). In addition, the antibiotics D-cycloserine and minocycline are promising in light of their ability to treat behavioral symptoms of ASD in clinical trials and animal models (52–54). Although both antibiotics are used to treat infections, their neuroprotective effects are commonly attributed to their roles as partial N-methyl-D-aspartate receptor agonist and microglial activation inhibitor, respectively. Read here.
This type of research is crucial to help so MANY. We need more treatments for these very ILL people. It is not a mental illness that afflicts them but instead, a gut and brain, hijacked by a DYSFUNCTIONAL MICROBIOME.
Can they be helped? Plenty of research is showing that to be true. Let's take a look at Minocycline. I do want to add that we need to consider that the way Minocycline might be helping is by killing bacteria in the gut. Remember that the microbiome has control over the microglia :
☤ Mazmanian’s group 9 have investigated the genesis of PD [ Parkinson's Disease ] features in mice genetically engineered to overexpress alpha-synuclein, which go on to develop features of PD. These mice are now one of the most widely used animal models in studying the disorder. Intriguingly, when they are raised germ-free (i.e., without gut microbes), their tendency to develop motor abnormalities is significantly reduced. When they are given a combination of short chain fatty acids, on the other hand, they show microglial activation in the brain and aggregation of alpha-synuclein with onset of motor features. These changes are inhibited by treatment with the antibiotic minocycline, which acts on a broad range of bacteria. If germ free alpha-synuclein overexpressing animals are given a humanized microbiota from a patient with PD, the emergency of pathology is far greater than those transplanting with the microbiota from a healthy subject. These findings pinpoint several potential lines of treatment, including the use of short-chain fatty acid antagonists, antibiotics, and microbiota transplantation. Read here.
☤ ...minocycline has been shown to be fairly well tolerated over longer periods of treatment and, as such, should be considered to be another option for the treatment of depression." Read here.
☤ One hypothesis claims that depression, or subsets of this disorder, is a microglial disorder, as the onset of depression often follows intense inflammatory episodes in the brain or, conversely, decline in microglial function (Yirmiya et al., 2015). Interestingly, minocycline, a tetracycline antibacterial agent known to inhibit the activation of microglia, can diminish depressive behaviors in rodents (Molina-Herna´ ndez et al., 2008; Zheng et al., 2015b) and humans (Miyaoka et al., 2012) and has been suggested as a potent antidepressant. In light of recent evidence on the role of the microbiome in microglia maturation and activation (Erny et al., 2015; Matcovitch-Natan et al., 2016), it is compelling to speculate that the microbiome impacts depression by influencing microglial maturation and activation. It should be noted, however, that it is yet to be determined whether the antidepressive effects of minocycline are due to its antimicrobial properties, inhibition of microglial activation, or a combination of the two. Read here.
☤ It was proposed that minocycline, a second-generation tetracycline, inhibits microglial activation and therefore affects neurodegenerative, neuropsychiatric and inflammatory diseases.102,103 However, it is not yet clarified how this ‘inhibition’ is generated. Orally administered minocycline can certainly affect the composition of the gut microbiota but is also well-absorbed and is able to penetrate the brain parenchyma and could inhibit microglia independent of the abundance of the microbiota.104 There is some evidence that minocycline attenuates the nuclear factor-jB pathway in microglia in vitro but the exact mechanism is not understood.105 Read here.
☤ antibiotic treatment alone using minocycline was able to “rebalance” the microbiota and was associated with blood pressure reduction. Read here.
☤ In MS, it is believed that minocycline works in an anti-inflammatory and neuroprotective manner. It may also work by influencing the bacteria in the gastrointestinal tract, known as the microbiome. Minocycline is known to improve the balance of organisms in the microbiome to be more anti-inflammatory. Read here.
☤ Importantly, note that whereas minocycline may promote autoimmune suppression by modulation of the intestinal microflora to repair the dysbiosis observed in MS patient, it can also have multiple direct immune-modulating effects that could contribute to the observed protection. Although minocycline may or may not ultimately prove beneficial in the context of MS, other oral antibiotics or combinations of antibiotics could be considered or developed in the future to promote anti-inflammatory communication along the gut–brian axis. Indeed, vancomycin was shown to improve the symptoms of autism in 8 out of 10 children studied (93). Read here.
☤ Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestoractive or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington’s disease, amyotrophic lateral sclerosis and Parkinson’s disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to the launching of various clinical trials. Previously, we reported the antipsychotic effects of minocycline in patients with schizophrenia. Read here.
I will also mention that a study was done on Regressive Autism and Minocycline Read here.. It took 9 years it appears, to determine that 10 children did not benefit. There was no placebo study group and no exclusions based on other medications so not sure that was a good way to evaluate Minocycline.
Minocycline has been used for decades to help with acne . Science now is showing that acne, along with other skin conditions, may have its origin in the gut microbiome:
☤ There is emerging evidence linking certain dermatological disorders to gut dysbiosis. However, this is not a novel topic and in fact, in 1911 a gastroenterologist named Milton H. Mack wrote, “Acne and eczema are both traceable to this fountainhead of diseases… if in a case of urticarial we look to the intestinal tract, why not in eczema and acne?” . Simultaneous gut and skin microbiome dysbiosis has been observed in several inflammatory skin diseases, such as rosacea, psoriasis, and atopic dermatitis. Read here.
SO as we near the month of APRIL and the BLUE LIGHTS to raise awareness of AUTISM, there are thousands of families drowning in fear and worry. The media shies away from these families as they do not understand THIS side of autism. They are not “feel good” stories about autism. It is tragic and the need for proper medical treatments is imperative. Minocycline may be a very hopeful intervention, especially as we see the increasing evidence of the autism specrum being connected to the spectrum of microbiome dysfunction.
Teresa Conrick is Science Editor for Age of Autism.