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

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

Tetra Discovery Partners today announced the initiation of a Phase 2 study of BPN14770 as a potential treatment for Fragile X Syndrome, the most common genetic form of autism. A selective small molecule inhibitor of the phosphodiesterase type-4D (PDE4D) subtype, 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.

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Fragile X Clinical Trial of New PDE4 Inhibitor from Tetra funded by FRAXA

Fragile X Clinical Trial of New PDE4 Inhibitor from Tetra funded by FRAXA

With a $200,043 grant from FRAXA Research Foundation in April 2018, Dr. Elizabeth Berry-Kravis will conduct a Phase 2 clinical trial of a new PDE4 inhibitor from Tetra Discovery Partners in adults with Fragile X syndrome.

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Takeaways from Fragile X Advocacy Day

Takeaways from Fragile X Advocacy Day

In the first week of March I attended my first Fragile X Advocacy Day to meet with many of the Massachusetts delegation to Congress. While this was my first time advocating for Fragile X research, I’ve been a longtime lung cancer research advocate and have met with many of the same representatives in the past. It was a pleasure to meet with many of the families as my participation in Advocacy Day was in the spirit of “we are all in this together”.

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Repurposing Study II: Evaluating Combinations of Drugs to Treat Fragile X

Repurposing Study II: Evaluating Combinations of Drugs to Treat Fragile X

FRAXA Research Foundation initially partnered with Healx in 2016 to identify existing drugs with potential to treat Fragile X syndrome, using machine learning algorithms and computational biology.  The study produced results, and now FRAXA and Healx have launched a new round of studies to evaluate combinations of compounds, including both drugs and natural products.

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In Their Own Words: Reports From the International Fragile X Workshop

In Their Own Words: Reports From the International Fragile X Workshop

The 18th International Fragile X and Related Neurodevelopmental Disorders Workshop in Quebec, Canada, was a great success, featuring Fragile X much more heavily than any previous meeting in this series! We asked our speakers to summarize their work in their own words. These brief updates from researchers investigating Fragile X.

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Development of a High-Content Synapse Assay to Screen Therapeutics for Fragile X Syndrome

Development of a High-Content Synapse Assay to Screen Therapeutics for Fragile X Syndrome

With a $45,000 grant from FRAXA Research Foundation in 2009, Dr. Mark Bear and Dr. Asha Bhakar used High Content Screening (HCS) to develop an assay sensitive to the effect of the FXS genotype. This project was funded in full by NIH after the first year.

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

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

Neuren’s Tofinetide Successful in Phase 2 Clinical Trial in Fragile X

Neuren’s Tofinetide Successful in Phase 2 Clinical Trial in Fragile X
One of the outcome measures - the new Fragile X Syndrome Rating Scale - showing positive results. Blue: placebo; Yellow: low-dose trofinetide; Green: high-dose trofinetide We are pleased to share great news adapted from Neuren’s press release: Neuren’s phase 2 trial has successfully established proof of concept and provides a strong rationale for Neuren to move forward with developing trofinetide for Fragile X syndrome. In this initial small trial with a relatively short treatment period, trofinetide was very well tolerated, with the high dose (70 mg/kg twice daily) demonstrating a consistent pattern of clinical improvement, observed in both clinician and caregiver assessments. After only 28 days of treatment, improvements were seen across core symptoms of Fragile X syndrome, including higher sensory tolerance, reduced anxiety, better self-regulation and more social engagement. No serious adverse events were reported. Positive Results in Fragile X Syndrome and Rett Syndrome Beneficial effects of trofinetide have now been observed in both FragileRead more

Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

With a $100,000 grant from the FRAXA Research Foundation in 2015, Dr. Peter Vanderklish explored a novel strategy to treat Fragile X syndrome: AMPK activators. The good news is that there are FDA approved (for example, metformin) and naturally occurring AMPK activators (such as resveratrol, found in red wine).

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Fruit Flies to Model and Test Fragile X Treatments

Fruit Flies to Model and Test Fragile X Treatments

Dr. Jongens and his collaborators have found an insulin-like protein in the fly brain that is overexpressed in the Fragile X mutant fly, leading to increased activity of the insulin signaling pathway. Furthermore, they found that certain behavioral patterns in the Fragile X flies can be rescued by expressing the FX gene just in insulin producing neurons in the fly brain. In the mutant, there are other changes in the signaling pathways, including a decrease in cAMP and elevation in PI3K, mTOR, Akt and ERK activity. They now propose to study 2 medicines used for diabetes: pioglitazone (increases cAMP and decreases Akt and ERK) and metformin (inhibits mTOR), in flies and mice to validate the potential efficacy of these novel therapeutics for Fragile X.

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FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

2015 Program Grant funded for $100,000 Mis-regulation of activity-dependent protein synthesis is one of the major cellular abnormalities found in Fragile X.  Upstream neuronal signaling regulates a large cluster of enzymes called the mTORC1 complex, which in turn regulates protein synthesis.  This complex is also controlled by cellular energy levels via the metabolic sensor AMP-activated Protein Kinase (AMPK).  AMPK is a highly conserved kinase that is activated under conditions of energy stress, when intracellular ATP levels decline and intracellular AMP increases.  AMPK normally mediates mTORC1 suppression, but AMPK appears to be decreased in Fragile X. Metformin, an FDA-approved drug, is widely used as a first-line therapy for type 2, and is a well known activator of AMPK.  It controls gene expression at the level of mRNA translation, comparable to the mTORC1 inhibitor rapamycin. This project will explore the potential of metformin and related compounds to rescue known abnormalities in Fragile

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FRAXA’s 2014 Top Goals

Complete Phase II/III Clinical Trials of mGluR5 Antagonists – and learn results Currently two large pharmaceutical companies – Novartis and Roche – are conducting large-scale clinical trials of experimental new medications for Fragile X syndrome which target the mGluR5 pathway.  The Novartis trial has finished enrolling adults and adolescents, while a pediatric trial is set to begin soon.  The Roche trial is well on the way to completion as well, but is still enrolling some age groups.  FRAXA has been working diligently to educate families about these trials in the hopes of getting them completed as quickly as possible.  Our goal (of course) is to discover whether these new drugs could be effective treatments for Fragile X, and to see these trials through to marketing of mGluR5 antagonists for Fragile X. Accelerate Clinical Trials of Investigational Treatments, based on research already funded by FRAXA New treatment strategies have emerged and

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Clinical Trials FAQ ← Frequently Asked Questions

Question: How Do Families Decide Which Trial is Best for Them? Answer: Each of the trials has different requirements for joining, so many – if not most – people will only be eligible for one trial after screening. The best way to approach this is to call the clinic contact closest to your area and discuss this with him/her. Age, weight, current medications, behavior, and IQ are all factors. When will the Trials be Finished? It all depends on enrollment. Trials need to have a certain number of people (a number determined before the trial starts) complete the trial before they can analyze the data and present results to the FDA. It all depends on how many people sign up to participate. Is There Assistance for Travel? Many trials provide financial assistance for travel expenses. The amount depends on how far you have to travel. Please check with the coordinatorRead more

Serotonergic Rescue of Synaptic Plasticity in FMR1 Knockout Mice

Serotonergic Rescue of Synaptic Plasticity in FMR1 Knockout Mice

With $306,000 in grants from FRAXA Research Foundation, Dr. Julius Zhu from the University of Virginia examined the effects of several drugs such as Buspar and Abilify which manipulate specific serotonin receptors and the effect that has on synaptic plasticity (LTP and LTD).

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

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