Archive for the ‘research’ Category

Anti-viral Therapy in Alzheimer’s- Clinical Trial

https://clinicaltrials.gov/ct2/show/NCT03282916

Anti-viral Therapy in Alzheimer’s Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03282916

Recruitment Status : Recruiting

First Posted : September 14, 2017
Last Update Posted : January 25, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Davangere P. Devanand, New York State Psychiatric Institute
Study Description
Brief Summary:
Anti-viral therapy in Alzheimer’s disease will investigate the efficacy of treating patients with mild Alzheimer’s disease with the U.S.A marketed generic anti-viral drug Valtrex (valacyclovir, 500mg oral tablet). Valacyclovir at 2 g to 4 g per day, repurposed to treat Alzheimer’s disease, will be compared to matching placebo in the treatment of 130 mild AD patients (65 valacyclovir, 65 placebo) who test positive for herpes simplex virus-1 (HSV1) or HSV2. The study will be a randomized, double-blind, 18-month Phase II proof of concept trial.
Condition or disease Intervention/treatment Phase
Alzheimer DiseaseHerpes Simplex 1Herpes Simplex 2 Drug: ValacyclovirDrug: Placebo Phase 2
Detailed Description:

Many viruses are latent for decades before being reactivated in the brain by stress, immune compromise, or other factors. After the initial oral infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and can later enter the brain via retrograde axonal transport, often targeting the temporal lobes.

HSV1 can also enter the brain via olfactory neurons directly. HSV1 (oral herpes) and HSV2 (genital herpes) are known to trigger amyloid aggregation and their DNA is commonly found in amyloid plaques. Anti-HSV drugs reduce Aβ and p-tau accumulation in brains of infected mice. HSV1 reactivation is associated with tau hyperphosphorylation in mice and may play a role in tau propagation across neurons. In humans, recurrent reactivation with newly produced HSV1 particles, ‘drop by drop,’ may produce neuronal damage and eventually lead to neurodegeneration and Alzheimer’s disease (AD) pathology, partly due to effects on amyloid and tau. Clinical studies show cognitive impairment in HSV seropositive patients in different patient groups and in healthy adults, and antiviral treatments show robust efficacy against peripheral HSV infection. The study team will conduct the first-ever clinical trial to directly address the long-standing viral etiology hypothesis of AD which posits that viruses, particularly the very common HSV1 and HSV2, may be etiologic or contribute to the pathology of AD.

In patients with mild AD who test positive for serum antibodies to HSV1 or HSV2, the generic antiviral drug valacyclovir, repurposed as an anti-AD drug, will be compared at oral doses of 2 to 4 grams per day to matching placebo in the treatment of 130 patients (65 valacyclovir, 65 placebo) in a randomized, double-blind, 78-week Phase II proof of concept trial. Patients treated with valacyclovir are hypothesized to show smaller decline in cognition and functioning compared to placebo, and, using 18F-Florbetapir PET imaging, to show less amyloid accumulation than placebo over the 78-week trial. Through the use of tau PET imaging with the tracer 18F-MK-6240 at baseline and 78 weeks, patients treated with valacyclovir are hypothesized to show smaller increases in 18F-MK-6240 binding than patients treated with placebo from baseline to 78 weeks. Apolipoprotein E genotype at baseline, as well as changes in cortical thinning on structural MRI, olfactory identification deficits, and antiviral antibody titers from baseline to 78 weeks, will be evaluated in exploratory analyses. In patients who agree to lumbar puncture, plasma and CSF acyclovir will be assayed to establish the degree of CNS penetration of valacyclovir in mild AD, and the investigators will obtain CSF Aβ42, tau, p-tau for subset exploratory analyses with changes in outcome measures.

If this trial is successful, the investigators will apply for funding to conduct a larger, multicenter, Phase III study using a study design that will be informed by the results of this Phase II trial. This innovative Phase II proof of concept trial clearly has exceptionally high reward potential for the treatment of AD.

Study Design
Go to  sections
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Anti-viral Therapy in Alzheimer’s Disease
Actual Study Start Date : February 12, 2018
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022
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**Comment**
Remember, Alzheimer’s is a label, nothing more.  They are still trying to figure out what causes it.
Dr. Klinghardt has gone on record stating that he’s not had one MS, ALS, or Parkinson’s patient NOT test positive for Lyme:  https://madisonarealymesupportgroup.com/2019/01/23/never-had-a-single-ms-als-or-parkinsons-patient-in-past-5-years-who-didnt-test-positive-for-lyme-dr-klinghardt/

Category:

Activism, Alzheimer's, research, Treatment, Viruses

Growing Importance of Lone Star Ticks in a Lyme Disease Endemic County

The growing importance of lone star ticks in a Lyme disease endemic county: Passive tick surveillance in Monmouth County, NJ, 2006 – 2016

Robert A. Jordan ,Andrea Egizi

PLOS

Published: February 12, 2019  https://doi.org/10.1371/journal.pone.0211778

Abstract

As human cases of tick-borne disease continue to increase, there is a heightened imperative to collect data on human-tick encounters to inform disease prevention. Passive tick surveillance programs that encourage members of the public to submit ticks they have encountered can provide a relatively low-cost means of collecting such data. We report the results of 11 years of tick submissions (2006–2016) collected in Monmouth County, New Jersey, an Atlantic coastal county long endemic for Lyme disease. A total of 8,608 ticks acquired in 22 U.S. states were submitted, 89.7% of which were acquired in Monmouth County, from 52 of the County’s 53 municipalities. Seasonal submission rates reflected known phenology of common human-biting ticks, but annual submissions of both Amblyomma americanum and Dermacentor variabilis increased significantly over time while numbers of Ixodes scapularis remained static. By 2016, A. americanum had expanded northward in the county and now accounted for nearly half (48.1%) of submissions, far outpacing encounters with I. scapularis (28.2% of submissions). Across all tick species and stages the greatest number of ticks were removed from children (ages 0–9, 40.8%) and older adults (ages 50+, 23.8%) and these age groups were also more likely to submit partially or fully engorged ticks, suggesting increased risk of tick-borne disease transmission to these vulnerable age groups. Significantly more people (43.2%) reported acquiring ticks at their place of residence than in a park or natural area (17.9%). This pattern was more pronounced for residents over 60 years of age (72.7% acquired at home). Education that stresses frequent tick checks should target older age groups engaged in activity around the home. Our results strongly suggest that encounter rates with ticks other than I. scapularis are substantial and increasing and that their role in causing human illness should be carefully investigated.

___________________

**Comment**

We’ve been told Amblyomma americium, .a.k.a Lone Star tick, only inhabits Southern states, and Dermacentor variabilis (Say), a.k.a. American dog tick or wood tick, is only found east of the Rocky Mountains, yet once again this proves the point ticks do not understand boundaries.  (Neither do birds, reptiles, deer, mice, fox, people, etc. – whom transport the ticks everywhere) 

The Lone Star tick is known to transmit Human Monocytic Ehrlichiosis, Tularemia, STARI, and is suspected of Lyme Disease and possibly Rocky Mountain Spotted Fever.  https://tickinfo.com/lonestartick

The CDC swears up and down it doesn’t transmit Lyme, yet, every advocate I know in the South says STARI looks, smells, and feels just like Lyme.  Patients in the South are tossed aside like yesterday’s garbage:  https://madisonarealymesupportgroup.com/2018/05/31/no-lyme-in-the-south-guess-again/

For the sordid history of the Southern Lyme/STARI fiasco, read here:  https://madisonarealymesupportgroup.com/2017/10/06/remembering-dr-masters-the-rebel-for-lyme-patients-who-took-on-the-cdc-single-handedly/  Excerpt:

Masters worked with Missouri entomologist, Dorothy Fier, who found borrelia in 2% of sampled lone star ticks and who supported Masters’ Missouri Lyme.  Despite publicity and validation, the CDC insisted that the EM rash was NOT diagnostic for LD for Missouri patients due to the fact that neither Ixodes dammini nor Ixodes pacificus were found there.

Masters worked with the CDC, who purposely tossed out data and manipulated the results.  Patients have been suffering ever since.

The wood tick is known to transmit Rocky Mountain spotted fever (RMSF), tularemia and can cause canine tick paralysis in dogs.  A high number of tularemia infected wood ticks have been found in Minnesota:  https://madisonarealymesupportgroup.com/2019/02/18/tularemia-in-minnesotan-ticks/  Across all sites, 128 (34%) of 378 pools were RT-PCR positive for F. tularensis.

Oops, that’s not supposed to happen….

 

 

 

 

Category:

Lyme, research, Ticks

High Prevalence of Bartonella in Spanish Veterinarians With Non-Specific Symptoms: Headache, Insomnia, Fatigue, & Memory Problems

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678790/

. 2017; 10: 553.
Published online 2017 Nov 7. doi: 10.1186/s13071-017-2483-z
PMCID: PMC5678790
PMID: 29116007

Prevalence of Bartonella spp. by culture, PCR and serology, in veterinary personnel from Spain

José A. Oteo,1 Ricardo Maggi,2 Aránzazu Portillo,1 Julie Bradley,3 Lara García-Álvarez,1 Montserrat San-Martín,4Xavier Roura,5 and Edward Breitschwerdtcorresponding author3

Abstract

Background

The genus Bartonella includes fastidious, facultative intracellular bacteria mainly transmitted by arthropods and distributed among mammalian reservoirs. Bartonella spp. implicated as etiological agents of zoonoses are increasing. Apart from the classical Bartonella henselae, B. bacilliformis or B. quintana, other species (B. elizabethae, B. rochalimae, B. vinsonii arupensis and B. v. berkhoffii, B. tamiae or B. koehlerae, among others) have also been associated with human and/or animal diseases. Laboratory techniques for diagnosis (culture, PCR assays and serology) usually show lack of sensitivity. Since 2005, a method based on a liquid enrichment Bartonella alphaproteobacteria growth medium (BAPGM) followed by PCRs for the amplification of Bartonella spp. has been developed. We aimed to assess culture, molecular and serological prevalence of Bartonella infections in companion animal veterinary personnel from Spain.

Methods

Each of 89 participants completed a questionnaire. Immunofluorescence assays (IFA) using B. vinsonii berkhoffii (genotypes I, II and III), B. henselae, B. quintana and B. koehlerae as antigens were performed. A cut-off of 1:64 was selected as a seroreactivity titer. Blood samples were inoculated into BAPGM and subcultured onto blood agar plates. Bartonella spp. was detected using conventional and quantitative real-time PCR assays and DNA sequencing.

Results

Among antigens corresponding to six Bartonella spp. or genotypes, the lowest seroreactivity was found against B. quintana (11.2%) and the highest, against B. v. berkhoffii genotype III (56%). A total of 27% of 89 individuals were not seroreactive to any test antigen. Bartonella spp. IFA seroreactivity was not associated with any clinical sign or symptom. DNA from Bartonella spp., including B. henselae (n = 2), B. v. berkhoffii genotypes I (n = 1) and III (n = 2), and B. quintana (n = 2) was detected in 7/89 veterinary personnel. PCR and DNA sequencing findings were not associated with clinical signs or symptoms. No co-infections were observed. One of the two B. henselae PCR-positive individuals was IFA seronegative to all tested antigens whereas the other one was not B. henselae seroreactive. The remaining PCR-positive individuals were seroreactive to multiple Bartonella spp. antigens.

Conclusions

High serological and molecular prevalences of exposure to, or infection with, Bartonella spp. were found in companion animal veterinary personnel from Spain. More studies using BAPGM enrichment blood culture and PCR are needed to clarify the finding of Bartonella PCR-positive individuals lacking clinical symptoms.

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**Comment**

While the abstract above doesn’t state this, the results section in the full study states of the 89 veterinary personnel from different regions of Spain:

A high percentage of the participants reported having chronic/ persistent non-specific symptoms such as headache, insomnia, fatigue or memory problems.

Veterinarians & those working with animals are especially at risk for Bartonella.  Spread the word.

More on Bartonella:  https://madisonarealymesupportgroup.com/2016/01/03/bartonella-treatment/

https://madisonarealymesupportgroup.com/2017/09/13/dr-fox-cat-scratch-fever-warning/

https://madisonarealymesupportgroup.com/2018/05/07/fox-news-bartonella-is-the-new-lyme-disease/

https://madisonarealymesupportgroup.com/2016/11/29/bartonella-seizures/

https://madisonarealymesupportgroup.com/2018/04/03/encephalopathy-in-adult-with-cat-scratch-disease/

https://madisonarealymesupportgroup.com/2017/01/04/endocarditis-consider-bartonella/

https://madisonarealymesupportgroup.com/2018/11/10/neurological-presentations-of-bartonella-henselae-infection/

https://madisonarealymesupportgroup.com/2017/10/23/opthalmic-manifestations-of-bartonella-infection/

 

 

 

Category:

Bartonella, research, Testing

Study Shows Peripheral Gamma-delta T-cell Proliferation After Tick Bite (Looks Like Cancer)

https://www.ncbi.nlm.nih.gov/pubmed/30702453

2019 Jan 22. doi: 10.1097/DAD.0000000000001352. [Epub ahead of print]

A Reactive Peripheral Gamma-Delta T-cell Lymphoid Proliferation After a Tick Bite.

Martin SM1, Flowers R, Saavedra AP, Gru AA2.

Abstract

Peripheral gamma-delta T-cell proliferations are encountered in reaction to certain infections and in primary malignancies. Identifying sources of benign reactions is key in avoiding unnecessary workup and surveillance of these aggressive malignancies. Borrelia infections have been implicated in a number of lymphoproliferative disorders, but rarely, if ever, in this setting. While gamma-delta T-cells are known to play a prominent role in the immune response to Borrelia infection, B-cell differentiation is encountered in the majority of Borrelia-associated proliferations. We present here a unique case of benign-appearing peripheral gamma-delta T-cell lymphoid proliferation in the setting of a tick-bite with subsequent erythema migrans-like skin findings.

________________

**Comment**

Again, nobody has a clue as to whether this is “unique” or not due to faulty antibody tests that are missing over half of all Lyme cases.  So many patients are flying under the radar and nobody’s looking. https://madisonarealymesupportgroup.com/2019/02/20/serology-test-for-lyme-virtually-worthless/  Again, many don’t present with the EM rash.  https://www.lymedisease.org/lymepolicywonk-how-many-of-those-with-lyme-disease-have-the-rash-estimates-range-from-27-80-2/

Many say this T-cell proliferation is perhaps more common than thought.

https://www.contagionlive.com/news/bystander-activation-of-t-cells-may-be-cause-of-persistent-arthritis-in-lyme-disease

The investigators now think they know how it’s happening. They have identified a T cell receptor that interacts with surface molecules on B. burgdorferi. According to the study, this interaction causes bystander activation of T cells, which in turn causes the T cells to produce inflammatory molecules that lead to arthritis symptoms around the joints.

Those activated T cells can continue to interact with residual bacteria long after the initial tick bite, meaning some patients continue to feel symptoms like arthritis…

They realized that T cells in the mice were undergoing bystander activation. “Instead of activating a very small, specific set of T cells, it causes this global activation of immune cells,” Ms. Whiteside said. Once activated, those T cells can interact with residual bacteria to generate continued inflammation even long after the initial infection.

Research possibilities are endless, yet most researchers either get hung up on climate change or fixate on the acute phase of Lyme.

https://madisonarealymesupportgroup.com/2019/02/10/wormsers-worthless-study-waste-of-taxpayer-money/

 

 

 

Category:

Lyme, research

Bystander Activation of T Cells May Be Cause of Persistent Arthritis in Lyme Disease & Why This Study is Incomplete

https://www.contagionlive.com/news/bystander-activation-of-t-cells-may-be-cause-of-persistent-arthritis-in-lyme-disease

Bystander Activation of T Cells May Be Cause of Persistent Arthritis in Lyme Disease

FEB 09, 2018 | JARED KALTWASSER
Investigators from the University of Utah Health believe they may have found the reason why some patients with Lyme disease have persistent arthritis even after antibiotic treatment. The news could pave the way to an effective treatment for a painful and confounding complication of Lyme disease.
“One of the clinical problems with Lyme disease infection is that there’s a small group of patients who continue to display symptoms, including arthritis symptoms, following what should be an effective treatment of antibiotics,” said Janis J. Weis, PhD, a professor of pathology at University of Utah Health, and a study author.

Dr. Weis said these symptoms persist in some patients even after there’s no longer evidence of an active infection with Borrelia burgdorferi, the bacteria that causes Lyme disease.

The investigators now think they know how it’s happening. They have identified a T cell receptor that interacts with surface molecules on B. burgdorferi. According to the study, this interaction causes bystander activation of T cells, which in turn causes the T cells to produce inflammatory molecules that lead to arthritis symptoms around the joints.

Those activated T cells can continue to interact with residual bacteria long after the initial tick bite, meaning some patients continue to feel symptoms like arthritis.

To get to those results, Dr. Weis and colleagues first had to find a suitable animal model, as reliable animal markers to study the inflammatory response had not existed until now. However, Dr. Weis stated that students in her lab realized that a specific set of mice—those lacking the anti-inflammatory molecule IL-10—had the same kinds of sustained inflammatory responses that were so troublesome in the small subset of Lyme disease patients with persistent arthritis.

Graduate student, Sarah Whiteside, the study’s first author, monitored these IL-10-deficient mice for more than 4 months post infection with B. burgdorferi.

“Sarah demonstrated that even 18 weeks after infection, the arthritis was still severe and there was a tremendous amount of joint inflammation in the joint tissue, but no evidence of bacteria in the joint tissue,” Weis told Contagion®.
They realized that T cells in the mice were undergoing bystander activation.
“Instead of activating a very small, specific set of T cells, it causes this global activation of immune cells,” Ms. Whiteside said.
Once activated, those T cells can interact with residual bacteria to generate continued inflammation even long after the initial infection.

The implications of the study are multiple. Ms. Whiteside shared that a next step will be to test the theory in humans to confirm whether bystander activation is also contributing to lingering symptoms in human patients with Lyme disease.

At the same time, identification of the IL-10 deficient mouse model could spark additional research and new therapies, such as a therapy to short-circuit T cell activation so as to mitigate the risk of persistent arthritis.

Further research may look into whether it is possible to identify which patients are most likely to have persistent symptoms. Thus far, we have no way of reliably identifying those patients, Dr. Weis stated, but she noted that research from Allen Steere, MD, of Massachusetts General Hospital, has suggested that certain genetic markers seem to be more common in patients who develop persistent arthritis with Lyme disease. Those markers are similar to the markers associated with rheumatoid arthritis (RA), she continued. However, that connection doesn’t appear to be found 100% of the time.

“It’s not an all-or-nothing kind of association,” stated Dr. Weis.
Still, the potential combination could suggest potential therapeutic options.
“Maybe drugs that are used to treat RA or drugs that can temporarily suppress the immune response could be applicable for this persistent arthritis,” added Ms. Whiteside.

__________________

**Comment**

Interesting article but a few points to consider:

  1. The group that continues to have symptoms isn’t small.  There’s a lot of us!  Microbiologist Holly Ahern states current research estimates 60% of patients suffer with chronic symptoms:  https://madisonarealymesupportgroup.com/2019/02/25/medical-stalemate-what-causes-continuing-symptoms-after-lyme-treatment/
  2. What is their definition of “effective treatment?”  There is heated debate on that topic:  https://madisonarealymesupportgroup.com/2017/05/05/the-reality-of-lyme-disease-not-just-two-camps-anymore/  If they are pushing the 21 days of doxycycline rubbish, current research has completely refuted it:  https://madisonarealymesupportgroup.com/2018/10/30/study-shows-lyme-msids-patients-infected-with-many-pathogens-and-explains-why-we-are-so-sick/  The issues of pleomorphism (shapeshifting), coinfections (other pathogens), biofilm,  pathogen persistence, and effective drug blood levels must be dealt with.
  3. Just because they haven’t found Bb, doesn’t mean it’s not there.  We know Bb travels everywhere within the body.  Until they are able to test every organ of the body, they are only stating they didn’t find it in the ONE place they looked.  Blood tests for Bb are abysmal.  Bb doesn’t hang out in the blood.  It’s a stealth organism that hides out and changes form.  One of the hallmarks of Lyme is it migrates.
  4. Her suggestion of immunopressive drugs will worsen many due to persistent infection.  LLMD’s have long known that immunosuppressive drugs make infection worse:  http://www.lymenet.de/literatur/steroids.htm  (Please remember not all steroids are bad.  There are anabolic and there are catabolic.  Big difference.)
  5. This article again highlights the importance of post-mortem studies needed to determine persistent/active infection:  https://madisonarealymesupportgroup.com/2018/04/13/chronic-lyme-post-mortem-study-needed-to-end-the-lyme-wars/
  6. http://  This short 7 min. video from Envita explains:The helper T-cells come along and pick up the processed antigen off the dendritic cell and then passes it along to the killer T cells. The Killer T cells follow the spirochete throughout the body and proceeds to destroy healthy tissues and organs because they can’t differentiate between the antigen of the spirochete and the antigen of healthy tissue.  As the killer T cells come into contact with the antigen on the healthy tissue it becomes inflamed and destroys healthy tissue and is autoimmune in nature.

This video was made in 2008.  I guess the authors missed it, as well as this groundbreaking study the video is based upon:  https://www.scirp.org/Journal/PaperInformation.aspx?PaperID=52890#.VK2lFivF8WI

 

 

 

Category:

Inflammation, Lyme, research, Testing