JUL 13, 2018 1:49 PM PDT

Pharmacological Strategy Attempts To Treat Multiple Symptoms of Fragile X

WRITTEN BY: Nouran Amin

Recent research in a mouse model of fragile X syndrome (FXS), scheduled for publication in Neuropsychopharmacology, shows that a pharmacological strategy can reduce multiple behavioral and cellular deficiencies in the most common inherited form of intellectual disability and a major single-gene cause of autism spectrum disorders.

When a compound, by the name GSK6A, was given to mice lacking the Fmr1 gene, an established animal model of fragile X syndrome, symptomatic behaviors were alleviated including impaired social interactions and decision making, displayed by individuals with fragile X syndrome.

Results showed that treatment with GSK6A, an inhibitor of a cellular signaling enzyme called p110β form of PI3 (phosphoinositide-3) kinase, may serve as a logical strategy for treating cognitive and behavioral problems in fragile X syndrome; the efficacy, of course, would be evaluated in human clinical trials.

"Our results suggest that p110β inhibitors can be repurposed for fragile X syndrome, and they have implications for other subtypes of autism spectrum disorders that are characterized by similar alterations of this pathway," says Gary Bassell, Ph.D., professor and chair of cell biology at Emory University School of Medicine. "Right now, no proven effective treatments are available for fragile X syndrome that are targeted to the disease mechanism," Gross says. "We think that p110β is an appropriate target because it is directly regulated by FMRP, and it is overactivated in both mouse models and patient cell lines."

To ensure that undesirable side-effects of the pharmacological strategy do not appear, the researchers are first planning long-term animal studies on p110β inhibitors in fragile X syndrome.

1 in 3000 males and 1 in 6000 females are affected with Fragile X and females often have milder symptoms. Affected children may display intellectual disability with a delay of milestones such as speech. They may also feature autism-like features including impaired social skills, gaze aversion/social anxiety, hyperactivity and repetitive behaviors.

FXS is a result the silencing of a single gene, FMR1, which prevents the production of an RNA binding protein known as FMRP. FMRP manages the production of several proteins at synapses, the sites of communication between neurons.

In the current study, short-term treatments are only considered which covers one or two injections. For one experiment, mice were treated for 10 days, which normalized their densities of dendritic spines present in the hippocampus. Synaptic structures are overabundant in the absence of FMRP in animals and humans with FXS.

"It is likely that PI3 kinase—in its various forms—needs to be kept in a tight balance at the synapse," Bassell says. "Too much or too little can tip things into a suboptimal zone, especially for complex behaviors. We think targeting the excess p110β in FXS can restore signaling between upstream and downstream defects linked to the absence of FMRP. We can't use mouse behavioral tests alone to understand a drug's effects," Bassell says. "It is critical to have molecular, cellular and neurophysiological phenotypes, which we and others do."

Source: Journal of Neuropsychopharmacology, Science Daily, Medical Xpress

 

About the Author
  • Nouran earned her BS and MS in Biology at IUPUI and currently shares her love of science by teaching. She enjoys writing on various topics as well including science & medicine, global health, and conservation biology. She hopes through her writing she can make science more engaging and communicable to the general public.
You May Also Like
SEP 20, 2020
Drug Discovery & Development
New Drug Shows Promise in Treating Advanced COVID-19
SEP 20, 2020
New Drug Shows Promise in Treating Advanced COVID-19
As the COVID-19 pandemic rages on, the search for drugs to combat the virus is ongoing. Now, scientists have found that ...
OCT 01, 2020
Cancer
Understanding in vivo Metabolomics: C13 Isotope Studies
OCT 01, 2020
Understanding in vivo Metabolomics: C13 Isotope Studies
One key to understanding cancer metabolomics lies in the ability to accurately replicate the natural environment of the ...
OCT 13, 2020
Immunology
Early Tips For Cell & Gene Therapy Regulatory Compliance
OCT 13, 2020
Early Tips For Cell & Gene Therapy Regulatory Compliance
Cell and gene therapies hold great promise for improved health outcomes. Now is the time to advance life-saving research ...
NOV 20, 2020
Drug Discovery & Development
Hyperbaric Oxygen Treatments Reverse Aging
NOV 20, 2020
Hyperbaric Oxygen Treatments Reverse Aging
Researchers from Israel have found that hyperbaric oxygen treatments (HBOT) in healthy aging adults can prevent blood ce ...
NOV 26, 2020
Immunology
Armed With ImmunoBait, Red Blood Cells Fight Lung Cancers
NOV 26, 2020
Armed With ImmunoBait, Red Blood Cells Fight Lung Cancers
  There’s a new weapon in the battle against lung cancer metastases: red blood cells equipped with nanopartic ...
NOV 18, 2020
Technology
Using Machine Learning to Build Chemical Libraries
NOV 18, 2020
Using Machine Learning to Build Chemical Libraries
Using machine learning in drug discovery is no longer a novel procedure and has been well documented in recent literatur ...
Loading Comments...