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 is a scientist, educator, and life-long learner with a passion for making science more communicable. When not busy in the lab isolating blood macrophages, she enjoys writing on various STEM topics.
You May Also Like
JAN 18, 2021
Immunology
Arthritis Drug Approved for Critically Ill COVID Patients
JAN 18, 2021
Arthritis Drug Approved for Critically Ill COVID Patients
Critically ill COVID patients in the U.K. may receive an arthritis drug after a study showed that treatment lowered mort ...
JAN 16, 2021
Drug Discovery & Development
Alternative Pain-Relief Bio-patch
JAN 16, 2021
Alternative Pain-Relief Bio-patch
Researchers develop a bio-compatible patch that releases non-opioid painkillers for days and potentially serving as a sa ...
MAR 04, 2021
Drug Discovery & Development
How Placebo Drugs for Pain Work in the Brain
MAR 04, 2021
How Placebo Drugs for Pain Work in the Brain
Researchers from Dartmouth College have found that pain relief drugs that work via the placebo effect reduce pain-relate ...
MAR 09, 2021
Cannabis Sciences
Cannabis Alleviates Neuropathic Pain from Chemotherapy
MAR 09, 2021
Cannabis Alleviates Neuropathic Pain from Chemotherapy
Neuropathic pain from oxaliplatin-based chemotherapy regimens occurs in up to 90% of patients, and continued exposure to ...
APR 22, 2021
Drug Discovery & Development
mRNA Covid Vaccines May Protect Against New Strains and Common Cold
APR 22, 2021
mRNA Covid Vaccines May Protect Against New Strains and Common Cold
Researchers from Johns Hopkins have found that the mRNA Covid vaccines developed by Pfizer and Moderna not only work wit ...
MAY 12, 2021
Technology
Belkin Laser Completes Enrollment for Trial Studying New Glaucoma Laser Treatment
MAY 12, 2021
Belkin Laser Completes Enrollment for Trial Studying New Glaucoma Laser Treatment
Belkin Laser, a small Israel-based biotechnology company, has announced that it has completed enrollment for its pivotal ...
Loading Comments...