Drug for Fragile X syndrome and autism - Printable Version
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Drug for Fragile X syndrome and autism - BojanaL - 12-05-2012
Fragile X syndrome is inherited disorder associated mostly with males. Most prominent features of the disease are mental retardation, autistic and stereotypic (repetitive) behavior. It results from FMR1 (fragile X mental retardation 1) gene impairment. FMR1 gene is located on the X chromosome and it is essential for normal mental development. Since males have only one copy of the X chromosome, impaired version of the gene will inevitably result in disease. Number of CGG triplet repeats in the FMR1 gene indicates whether gene is healthy or mutated (fully mutated gene contains > 200 repeats) and serves as a marker in genetic testing for people who are at risk of getting offspring with disease. Fragile X is also known as single-gene cause of autism. Except drugs that are used to prevent hyperactivity, anxiety, aggressiveness (known symptoms of the disease), there is no single marketed drug that is specifically designed to treat social aspect of the fragile X syndrome.
Autism is neurodevelopmental disorder. It is characterized by impaired social and communication skills, and repetitive and restrictive behavior. Genetic background of disease is not fully revealed. Investigators are not certain if disease develops after rare genetic variants are combined (several genes are implicated) or as a consequence of rare genetic mutation. Sometimes, agents that induce birth defects (heavy metals, vaccines, toxins…) could trigger autism development. Estimated costs for an individual diagnosed with autism are ~3.99 million dollars for a lifetime. Disorder is “expensive” because autistic persons demand special medical care, special education and they rarely become capable to work and earn independent from their guardians. There is no known cure for autism. Children are usually treated with antipsychotics, anticonvulsants and antidepressants to alleviate some of the disease symptoms.
Recently published article announced that fragile X syndrome initially developed drug could be beneficial for the people diagnosed with autism. Researchers didn't have necessary data about dysfunctional brain pathways associated with altered behavior (typical for neurodevelopmental disorders), but recent experiment on genetically altered animals provided more information on potential biochemistry behind disease. Experiments on the mouse with fragile X showed lower level of gamma aminobutiryc acid (neurotransmitter) in various brain areas, including hippocampus (associated with memory, activity and orientation). Scientists hypothesized that lack of this neurotransmitter could trigger social anxiety and avoidance - typical fragile X associated behavior. Arbaclofen (or STX 209) acts like gamma aminobutyric acid type B agonist (synthetic imitator). It produces the same physiological effect as naturally (organism derived) substance and compensates the lack of gamma aminobutyric acid in the body. When tested in mice, drug showed great reduction of repetitive and anti-social behavior. Study in humans showed equally promising effects. It lasted for 2 years and comprised of mostly male fragile X sufferers aged 6 to 39. Drug was submitted in 2 doses per day during six weeks. After last dose was applied, 4 to 6 weeks long pause was made before participants were evaluated. Participants were monitored for: irritability, lethargy, repetitive behavior, hyperactivity… Social avoidance and parent-nominated problem behaviors showed improvement in all subjects. Arbaclofen could be of great help in treatment of autism due to high similarity of social and behavior problems with fragile X syndrome. Future trials will provide more information on drug safety and effectiveness in both disorders.
Since pharmacological treatment is still unavailable, another treatment option should be tested. Previous studies with horses and dolphins showed that autistic children manage to relax and socialize when they are near these animals. Latest study showed that almost any animal species (dogs, cats, rabbits, hamsters…) could produce similar healing effect. Autistic kids experience difficulties in recognizing other people’s emotions and needs and animals could learn them various important skills such as ability to share and provide comfort when needed. Trick is to introduce animal to a family later. If animal is already present when autistic children is born, animal will be considered as a part of normal environment and children wouldn’t change his own behavior to comfort the animal. Also, when animal is brought to the family, interaction between the family members will change and become more intense and warmer, which will significantly affect behavior of autistic children. You just need to decide which animal species suits you the best.
RE: Drug for Fragile X syndrome and autism - ExpertScie - 12-16-2012
“Many a times, Journey is more beautiful than destination”
Each step of development in medical science brings new hope and new life to millions and billions of patients, all around the world. One such developmental step is in the field of treatment of “Fragile x syndrome”. A new therapeutic strategy has been developed and is with lot of potential. This research was led by Dr. Lucia Ciranna at the University of Catania in Italy.
In this field, a decade back, it was observed that blocking mGluR5 gave promising results in the treatment of Fragile X syndrome. Blocking mGluR5 therefore has been identified as potential way to treat Fragile X syndrome and many drugs were tested for the same. One such drug known as fenobam was beneficial in adults with FXS.
But further, Ciranna and colleagues seems to have identified other potential mechanisms for FXS. In this they showed that blockade of serotonin 7 (5-HT7) receptor, like mGluR5 greatly reduces long term depression mediated by mGlu receptors. Depression in neuroscience is nothing but reduction in ability of nerve cells to communicate or decrease in neuronal synapses or in its effectiveness.
More importantly this effect was detected in one of the brain structure which is mostly involved in learning and memory, that is hippocampus.
This research and its results had given a new way in the therapy of Fragile X Syndrome. Thus now selective agonists for receptors 5-HT7 can be used as pharmacological and medical tool for treatment. This study further identified a new compound LP-211 which has high affinity as well as selectivity towards 5-HT7 receptors. This way the data showed that LP-211 act as agonist of 5-HT7 receptor.
Thus a potential new treatment for Fragile X syndrome is on its way, starting form mGluR5 up to LP-211 and its clinical trials!
I am not sure whether it is true for all that “Any journey is more beautiful than destination”
But, definitely I can say that for any researcher or scientist who dedicate his decades of life in finding a thing or a new molecule, it is true!
RE: Drug for Fragile X syndrome and autism - lyka_candelario - 09-08-2013
Fragile X Syndrome (FXS) has two other names: Escalante’s Syndrome and Martin-Belle Syndrome. It involves intellectual disabilities ranging from mild to severe, physical attributes, and behavioral characteristics.
For the physical appearance, patients with FXS have an elongated face, large protruding ears, high arched palate, hyperextensible finger joints, soft skin, larger than normal testes, hypotonia, and flat feet. Sinusitis and middle ear infection is common in early childhood. Nervousness can be observed in speech.
Some individuals may meet the diagnostic criteria for autism. Common behavioral characteristics, as mentioned in the article, are limited eye contact, shyness, atypical social development, and stereotypic movements.
Intellectual difficulties include short-term memory, spared verbal abilities, visual memory, and visual-spatial relationships. It is also the leading genetic cause of autism. Since FXS individuals also have difficulty in face encoding, they get to experience a great deal of panic attacks which may also related to their excessive shyness. They may have mild to severe social withdrawal as well. Even with this, most of the males affected tend to have attention deficit hyperactivity disorder (ADHD). Expressions of anxiety can appear with hand flapping, biting, and aggression. There are also occurrences of phobic anxiety, somatization, interpersonal sensitivity, obsessive-compulsive disorder, depression, and psychoticism.
Strabismus and refractive errors are also common in patients with FXS. Seizures may also develop in some individuals as well as ataxia or tremors at a later age. Also, older patients will appear to have more difficulty in memory. Women with FXS are also affected with primary ovarian insufficiency which is like an early menopause.
There is no cure for FXS, however there are several symptom-managing medications used to lessen the secondary characteristics related to the condition. Stimulants are given for impulsivity, hyperactivity, and attention-associated problems. For anxiety, OCD behaviors, and mood disorders, antidepressants like Selective Serotonin Reuptake Inhibitors (SSRIs) are used. To treat aggressive and self-injurious behaviors, antipsychotics like Seroquel and Risperdal are given. Anticonvulsants are administered for seizures, and in some studies Lithium has shown to help in behavioral functioning. Speech, behavioral, and occupational therapy are its non-pharmacological treatment.
RE: Drug for Fragile X syndrome and autism - Alyssa03 - 09-19-2013
What ever the names it has be, Fragile is injurious to health. The way by it spreading it should be stopped by using any means whether it is possible or not means to use it any way just to forbid it.