Alzheimer's Archives • Fragile X Research

Tetra Announces $40M to Advance BPN14770 for FXS and Alzheimer’s Disease

FRAXA Research Foundation FRAXA Updates • Research Updates December 19, 2018December 19, 2018Alzheimer's, BPN14770, FDA, FRAXA-DVI, PDE4, Tetra Discovery Partners

Tetra Discovery Partners has signed a multi-part deal that could bring it up to $160 million, plus royalties, from Shionogi & Co, Ltd, a Japanese major research-driven pharmaceutical company. Tetra currently is conducting an investigational Phase 2 study of BPN14770 in adults with Fragile X Syndrome, an indication for which BPN14770 has received Orphan Drug Designation from the US Food and Drug Administration. This clinical trial was made possible by early work with the FRAXA-DVI and over $200,000 from FRAXA.

Metformin and Aberrant Insulin Signaling in a Fragile X Mouse Model

FRAXA Research Foundation 2017 Grants • 2018 Grants • Current Research Grants • Disease Mechanisms • Gantois, Ilse • McGill University • Sonenberg, Nahum • Treatment Targets November 2, 2018November 20, 2018Alzheimer's, autism, cancer, Fragile X Research Foundation of Canada, metformin

This 2017-2018 grant of $90,000 is funded jointly by FRAXA and the Fragile X Research Foundation of Canada for the first year. A previous FRAXA grant to the Sonenberg lab has led to great interest in the available drug, metformin, as a potential treatment for Fragile X syndrome. FRAXA is currently organizing clinical trials of metformin.

Fragile X Farm Life is Taylor’s World – Stevenson Family Campaign

FRAXA Research Foundation Fundraising Campaigns October 31, 2018December 27, 2018Alzheimer's, autism

Our world was turned upside down when Taylor was diagnosed at age 2 with Fragile X syndrome. We are thrilled that Taylor is busy, safe, happy and well cared for, living the simple farm life, though 22 years ago this was not the path we had envisioned for him. As a true apple lover, we’ve heard Taylor will pick an apple and give it a kiss before placing it in a basket. He’s also known as “the best chicken man there” as he is one of the few residents not afraid to go boldly into the coop and take the eggs from the chickens.

Mega Green Tea Extract to Treat Fragile X?

Hannah Maria Miles de la Torre, Rafael • Dierssen, Mara • Research Updates August 22, 2018January 14, 2019Alzheimer's, estrogen

Green tea is thought to have many benefits, particularly in cognitive function. In 2012-14, FRAXA Research Foundation funded a clinical trial to assess the effects of EGCG (green tea extract) on cognitive function in adults with FXS. Drs. Rafael de la Torre and Mara Dierssen Sotos, principal researchers in Barcelona, Spain, reported many positive results. After the extract was no longer administered, effects remained stable. Memory, attention, and mental flexibility improvements were still observable at least 3 months after treatment ended.

Tetra Discovery Partners Initiates Phase 2 Trial of BPN14770 in Fragile X Syndrome

FRAXA Research Foundation Berry-Kravis, Elizabeth • Rush University Medical Center July 10, 2018January 14, 2019Alzheimer's, autism, BPN14770, FDA, PDE4, sleep, Tetra Discovery Partners

This 2-Period Crossover Study of BPN14770 is accepting adults males with Fragile X syndrome at Rush University Medical Center in Chicago. Principal Investigator of the study is Elizabeth Berry-Kravis, MD, PhD.
A selective inhibitor of the phosphodiesterase type-4D (PDE4D), BPN14770 has shown the ability to improve the quality of connections between neurons and to improve multiple behavioral outcomes in the Fragile X mouse model.

Fragile X Clinical Trial of New PDE4D Inhibitor from Tetra funded by FRAXA

FRAXA Research Foundation 2018 Grants • Berry-Kravis, Elizabeth • Clinical • Clinical Trials • Current Research Grants • Recruiting • Rush University Medical Center April 5, 2018January 14, 2019Alzheimer's, BPN14770, cyclic AMP, FDA, FRAXA-DVI, PDE4, Pierce Family Fragile X Foundation, Tetra Discovery Partners

FRAXA Research Foundation has funded a clinical trial of an investigational new drug, led by Dr. Elizabeth Berry-Kravis at the Rush Fragile X Clinic in Chicago. This trial will treat 30 adult males with Fragile X syndrome with a PDE4D allosteric inhibitor from Tetra Discovery Partners using in a crossover design, so that everyone gets active drug for part of the time and placebo for part of the time.

Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI)

FRAXA Research Foundation 2011 Grants • 2012 Grants • 2013 Grants • 2014 Grants • 2015 Grants • 2016 Grants • 2017 Grants • 2018 Grants • Biomarkers • Carullo, Paulina • Cogram, Patricia • Current Research Grants • Drug Repurposing • FLENI Foundation • Resources • University of Chile October 1, 2017January 14, 2019Alzheimer's, EEG, FRAXA-DVI, seizure

The FRAXA Drug Validation Initiative (FRAXA-DVI) provides speedy, cost-effective, objective preclinical testing of potential new Fragile X treatments. FRAXA has funded FRAXA-DVI for $50,000 or more per year since 2012.

Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

Theodore Coutilish 2016 Grants • 2017 Grants • 2018 Grants • Biomarkers • Current Research Grants • Treatment Targets • University of Wisconsin • Westmark, Cara May 23, 2017August 29, 2018Alzheimer's, amyloid precursor protein, autism, EEG, seizure, sleep, sound

FRAXA Research Foundation awarded $122,000 over 2016-2018 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.

NIH Investigator Carolyn Beebe Smith, PhD, Looks to Improve Sleep in Fragile X Syndrome

Theodore Coutilish Research Updates • Smith, Carolyn B. November 17, 2016July 2, 2018Alzheimer's, autism, baclofen, FDA, lithium, sleep

Our sons with Fragile X Syndrome typically go to bed early and rise early. Sometimes they jump on us while we are sleeping at 3 a.m., excited to start their day. For heaven’s sake, whY, wHY, WHY? The answer may come from Carolyn Beebe Smith, PhD, senior investigator, Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. She is studying why children, in particularly boys, with FXS have problems sleeping. “We know sleep is important for many aspects of brain function,” said Dr. Smith, who received a PhD from the University of London where she studied the chemical pathology of Alzheimer’s for which she was awarded the Queen Square Prize. “In studies of healthy mice, we have shown restricted sleep during brain development can result in long-lasting changes in behavior. We are interested in understanding if sleep problems contribute to severity ofRead more

New compound from Anavex Improves Learning and Behavior in Fragile X Mice

FRAXA Research Foundation Research Updates June 6, 2016July 26, 2018Alzheimer's, autism, Fragile X Meeting, Rett syndrome

A potential new treatment for Fragile X syndrome is showing promise. While still early in development, the investigational drug was able to improve intellectual, learning and hyperactivity measures in a mouse model of Fragile X syndrome. Anavex 2-73 is a sigma-1 receptor agonist being developed for autism spectrum disorders, including Rett syndrome and Fragile X syndrome, and for Alzheimer’s disease. Anavex Life Sciences presented the data at the Gordon Research Conference for Fragile X and Autism-Related Disorders, held June 5-10, 2016 in Mount Snow, VT. The study was sponsored by FRAXA, via the FRAXA Drug Validation Initiative, and performed by Fraunhofer Chile Research, in Santiago, Chile. “The ANAVEX 2-73 data in an array of behavioral paradigms in a validated mouse model of Fragile X is very encouraging. The results are promising for both Fragile X syndrome and Autism Spectrum Disorders, since there is an overlap in the clinical as well asRead more

Can STEP Inhibitors Treat Fragile X Syndrome? Yale Professor Investigates

Theodore Coutilish Research Updates March 28, 2016July 23, 2018Alzheimer's, STEP (STriatal-Enriched protein tyrosine Phosphatase)

Yale Professor Paul Lombroso, MD, looks to improve cognitive and social behaviors in those affected by Fragile X thanks to FRAXA support It’s been 25 years since Paul Lombroso, MD, first discovered the STEP protein (STriatal-Enriched protein tyrosine Phosphatase). In its simplest terms, STEP is a protein found only in the brain; is critical as people learn and develop social behavior; impacts how short memory becomes long-term memory; and regulates synapsis strengthening and intracellular signaling. When STEP elevates, as occurs in those with Fragile X syndrome and many other disorders, it significantly impacts cognitive and memory development and social behaviors. “My first decade of research was to understand STEP,” said Lombroso, the Elizabeth Mears and House Jameson Professor in the Child Study Center and the Director of Laboratory of Molecular Neurobiology, Yale University. “What was it doing in the brain …. what was it regulating?” Now Lombroso is engaged inRead more

Crossroads of Fragile X and Alzheimers Research

FRAXA Research Foundation Research Updates July 20, 2015July 9, 2018Alzheimer's, amyloid precursor protein, autism

Claudia Bagni, PhD, an author of the new study published in Neuron and a previous recipient of a FRAXA research grant Researchers Investigate Treatment Targets Which May Address Both Fragile X Syndrome and Alzheimer’s Disease Last week researchers at VIB Leuven in Belgium published evidence that a brain pathway involving the protein APP (Amyloid Precursor Protein) plays a vital role in development of Fragile X syndrome, one of the most common causes of autism. Scientists led by Dr. Emanuela Pasciuto in the laboratory of Prof Claudia Bagni published findings of their study in the journal Neuron. The team identified the molecular mechanisms behind the elevated levels and metabolism of APP protein in a mouse model. This dysregulation affects brain development and behavior, at a stage where the infant’s neuronal connections i.e. synapses are being formed and remodeled. Using a newly developed agent the team was able to reduce the cellular dysfunctionRead more

Bryostatin Restores Learning and Memory in Adult Fragile X Mice

FRAXA Research Foundation Research Updates March 11, 2015July 23, 2018Alzheimer's, BDNF, cancer, FRAXA-DVI, GSK3, PSD-95

Just as the Amazon rainforest may hold a cure for cancer if only scientists can find it, a bizarre marine critter found off the California coast — Bugula neritina— is the only known source of a potential new Fragile X treatment, Bryostatin. Last month, FRAXA sat down with scientists from Neurotrope BioScience, a specialty biopharmaceutical company developing medicines for rare diseases and Alzheimer’s based on Bryostatin. Their Fragile X program is based on research by a West Virginia team led by Daniel Alkon, MD, which showed that Bryostatin-1 restores hippocampal synapses and spatial learning and memory in adult Fragile X mice. “Our results show that synaptic and cognitive function of adult FXS mice can be normalized through pharmacologic treatment and that bryostatin-1-like agents may represent a novel class of drugs to treat Fragile X mental retardation even after postpartum brain development has largely completed,” remarked Dr. Alkon. Bugula and Bryostatins Often mistaken for seaweed, bugula is actually colonies of small animals, likeRead more

Functional Interplay Between FMRP and CDK5 Signaling

FRAXA Research Foundation 2011 Grants • 2012 Grants • 2013 Grants • 2014 Grants • Biomarkers • Completed Research Grant • Disease Mechanisms • Emory University • Feng, Yue • Li, Wenqi • Treatment Targets September 13, 2014April 25, 2018Alzheimer's, CDK5, GABA, MAP1b, mGluR5, mRNAs

With a $180,000 grant from the FRAXA Research Foundation over 2011-2014, Dr. Yue Feng and Dr. Wenqi Li at Emory University will study CDK5 pathway function and regulation in an effort to break down whether and how CDK5 signaling is affected by the loss of the Fragile X protein, FMRP, in the Fragile X mouse model.

Functional Interplay Between FMRP and CDK5 Signaling

FRAXA Research Foundation Uncategorized April 24, 2014January 24, 2018Alzheimer's, CDK5, GABA, MAP1b, mGluR5, mRNAs

Yue Feng, PhD — Emory University School of Medicine with Wenqi Li, PhD, Postdoctoral Fellow FRAXA Awards: $180,000 $45,000 in 2013 renewed for $45,000 in 2014 $45,000 in 2011 renewed for $45,000 in 2012 Weakened synaptic development and synaptic plasticity, as a result of lacking the functional Fragile X protein (FMRP), underlies the intellectual disability in Fragile X Syndrome (FXS). Decades of investigation established the role of FMRP in binding its mRNA targets and regulating translation in response to neuronal and synaptic activity changes. Exciting discoveries on two receptors, mGluR5 and GABA, signaling in FXS animal models have led to promising therapeutic approaches based on variation of synaptic activity by mGluR5 antagonists and GABA agonists. However, clinical trials only achieved partial reverse of FXS phenotype. Thus, developing additional therapeutic strategies for treating the full spectrum of FXS symptoms are still pressing challenges. The identification of genome-wide Fragile X protein (FMRP) target mRNAs by recent discoveries provides important clues

What Treatments Work for FXTAS?

Michael Tranfaglia, MD Community March 25, 2014June 21, 2018Alzheimer's, FXTAS, glutamate

Many older family members in the Fragile X community are affected by FXTAS (Fragile X-associated Tremor/Ataxia Syndrome). We all hope that knowing the underlying cause of neurodegenerative symptoms in FXTAS will help in the development of specific treatments over the long term. In the short term, we would also hope that having a specific diagnosis would help us to identify particular available treatments which might be more effective than others. One of the available treatments for Alzheimer's Disease is a glutamate receptor blocker called memantine (Namenda), and dementia specialists think this drug could be effective in treating a wide range of neurodegenerative diseases. It has been found to be effective in treating Lewy Body Dementia, a disorder which causes parkinsonism and cognitive decline, with features rather similar to FXTAS. This led researchers to think that this drug could also be useful in treating FXTAS, and initial open-label experience with it wasRead more

Ab-Mediated Translation in Fragile X Syndrome

FRAXA Research Foundation 2011 Grants • 2012 Grants • Biomarkers • Completed Research Grant • Treatment Targets • University of Wisconsin • Westmark, Cara September 13, 2012April 25, 2018Alzheimer's, LTD (Long-term depression), mGluR, mGluR5, mRNAs

With a $120,000 grant from FRAXA Research Foundation during 2011-2012, Dr. Cara Westmark at the University of Wisconsin explored the role of AbPP as a potential treatment option for fragile X. AbPP produces b-amyloid which is over-expressed in Alzheimer’s disease (AD) and Down syndrome.

What Works, and What Doesn’t

Michael Tranfaglia, MD Research Updates September 7, 2012June 21, 2018Alzheimer's, AMPAkines, autism, BK channel, cancer, ERK, GABA, GSK3, lithium, mGluR5, minocycline

At the start, it’s always hard to know what methods will work best for something as complex as the development of disease-modifying treatments for Fragile X. But, we’ve always tried to let the science lead us down the right path. At this point, the results are unequivocal, and they have shaped how we are looking for the Next Great Thing in Fragile X treatments. As a bit of background, it’s worth noting that there are two basic ways of approaching treatment research for any disease: rational drug discovery vs. high-throughput screening. Rational drug discovery means exploring the basic mechanism of disease and identifying specific “treatment targets” that might be expected to correct the underlying problem. Usually, the target is an enzyme (a protein which facilitates biochemical reactions in the cell) or a receptor (a protein, usually on the cell surface, which detects small amounts of a chemical messenger, such asRead more

Compound that Inhibits mGluR5 Corrects Signs of Fragile X in Adult Mice

Michael Tranfaglia, MD Research Updates April 13, 2012July 23, 2018Alzheimer's, amyloid precursor protein, autism, glutamate, hypersensitivity, mGluR, mGluR5, Roche, sound

A study finds that a new compound reverses many of the major symptoms associated with Fragile X syndrome (FXS). The paper is published in the April 12 issue of the journal Neuron, describes the exciting observation that the FXS correction can occur in adult mice, after the symptoms of the condition have already been established. Previous research has suggested that inhibition of mGlu5, a subtype of receptor for the excitatory neurotransmitter glutamate, may ameliorate many of the major symptoms of the disease. This study, a collaboration between a group at Roche in Switzerland, led by Dr. Lothar Lindemann, and Dr. Mark Bear’s MIT lab, used an mGlu5 inhibitor called CTEP to examine whether inhibition of mGlu5 could reverse FXS symptoms. The researchers gave CTEP to mice which model Fragile X. "We found that even when treatment with CTEP was started in adult mice, it reduced a wide range of FXSRead more

Role of JNK in FMRP Regulated Translation in Fragile X Syndrome

FRAXA Research Foundation 2011 Grants • 2012 Grants • Completed Research Grant • Disease Mechanisms • Treatment Targets • University of Wisconsin • Wilhelm, Michael January 31, 2012April 25, 2018Alzheimer's, amyloid precursor protein, mGluR, mGluR5, mRNAs

With a $90,000 grant from FRAXA Research Foundation over 2 years, Dr. Michael Wilhelm and his team at the University of Wisconsin studied a protein known as JNK, which is observed to be abnormally regulated in Fragile X. Like FMRP, it is involved in regulating dendritic protein synthesis, and so it may be a target for drug therapy in Fragile X.

FRAXA Research Outlook 2012 – Treatment Trials and the Next Wave of New Drugs

Michael Tranfaglia, MD Research Updates December 27, 2011July 14, 2018AFQ056, Alzheimer's, arbaclofen, autism, baclofen, basimglurant, FDA, glutamate, GSK3, lithium, mGluR5, minocycline, Novartis, PAK (p21-activated kinase), PDE4, Roche

Treatment Trials As you probably know, three pharmaceutical companies are conducting clinical trials in Fragile X. Two Swiss giants, Novartis and Roche, are racing to get their lead mGluR5 antagonists to market, and U.S. startup Seaside Therapeutics is pursuing a compound which targets the brain receptor, GABAB. Novartis has large-scale Phase IIb/III trials of the drug AFQ056 well underway. Sites worldwide are enrolling adolescents and adults, with 35 more adults needed and recruitment of adolescents planned through Fall 2012. At this point, some participants have already completed the placebo-controlled trial and are now taking AFQ056, with the option of continuing it until it reaches the market. Novartis is also working toward a trial of AFQ056 for younger children with Fragile X. Roche completed a Phase II trial of its mGluR5 antagonist (currently with the catchy name of RO4917523) last year and is about to commence a larger Phase II trialRead more

Using Fenobam to Reduce APP and Abeta in Fragile X Mice

FRAXA Research Foundation 2006-2010 Grants • Completed Research Grant • Malter, James • Treatment Targets • University of Wisconsin • Westmark, Cara February 14, 2008August 9, 2018Alzheimer's, Amyloid beta, amyloid precursor protein, fenobam, mGluR5, seizure

With a $130,000 grant from FRAXA Research Foundation over 2008-2008, Drs. James Malter and Cara Westmark at the University of Wisconsin studied the relationship between the Fragile X protein FMRP and APP, a protein important to the pathology of Alzheimer’s Disease. APP may also contribute to the pathology of Fragile X, and its major metabolite, Aß, may contribute to abnormal protein synthesis via a positive feedback loop. This project sought to restore normal dendritic protein synthesis in Fragile X mice by breaking into this loop.