Down Syndrome

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Drug reverses age-related cognitive decline within days


Rapid mental rejuvenation in old mice suggests age-related losses may be broadly reversible 

"Limiting children's screen time linked to better cognition," reports BBC News.


Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice, according to a new study by UC San Francisco scientists. The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome , prevent noise-related hearing loss, fight certain types of prostate cancer , and even enhance cognition in healthy animals.

In the new study, published December 1, 2020 in the open-access journal eLife , researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.


“ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological “blockage” rather than more permanent degradation,” said Susanna Rosi , PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science (http://ptrehab.ucsf.edu/) .

“The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress,” added Peter Walter , PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. “Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time.”


Could Rebooting Cellular Protein Production Hold the Key to Aging and Other Diseases?

Walter has won numerous scientific awards, including the Breakthrough , Lasker  and Shaw  prizes, for his decades-long studies of cellular stress responses. ISRIB, discovered in 2013 in Walter’s lab, works by rebooting cells’ protein production machinery after it gets throttled by one of these stress responses — a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).

The ISR normally detects problems with protein production in a cell — a potential sign of viral infection or cancer-promoting gene mutations — and responds by putting the brakes on cell’s protein-synthesis machinery. This safety mechanism is critical for weeding out misbehaving cells, but if stuck in the on position in a tissue like the brain, it can lead to serious problems, as cells lose the ability to perform their normal activities, Walter and colleagues have found.

In particular, recent animal studies by Walter and Rosi, made possible by early philanthropic support from The Rogers Family Foundation, have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.

The cognitive deficits in TBI patients are often likened to premature aging, which led Rosi and Walter to wonder if the ISR could also underlie purely age-related cognitive decline. Aging is well known to compromise cellular protein production across the body, as life’s many insults pile up and stressors like chronic inflammation wear away at cells, potentially leading to widespread activation of the ISR.

“We’ve seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline,” said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. “It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step.”

ISRIB Improves Cognition, Boosts Neuron and Immune Cell Function

In the new study, researchers led by Rosi lab postdoc Karen Krukowski , PhD, trained aged animals to escape from a watery maze by finding a hidden platform, a task that is typically hard for older animals to learn. But animals who received small daily doses of ISRIB during the three-day training process were able to accomplish the task as well as youthful mice, much better than animals of the same age who didn’t receive the drug.

The researchers then tested how long this cognitive rejuvenation lasted and whether it could generalize to other cognitive skills. Several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily — a test of mental flexibility for aged mice who, like humans, tend to get increasingly stuck in their ways. The mice who had received brief ISRIB treatment three weeks before still performed at youthful levels, while untreated mice continued to struggle.

To understand how ISRIB might be improving brain function, the researchers studied the activity and anatomy of cells in the hippocampus, a brain region with a key role in learning and memory, just one day after giving animals a single dose of ISRIB. They found that common signatures of neuronal aging disappeared literally overnight: neurons’ electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.

The researchers are continuing to study exactly how the ISR disrupts cognition in aging and other conditions and to understand how long ISRIB’s cognitive benefits may last. Among other puzzles raised by the new findings is the discovery that ISRIB also alters the function of the immune system’s T cells, which also are prone to age-related dysfunction. The findings suggest another path by which the drug could be improving cognition in aged animals, and could have implications for diseases from Alzheimer’s to diabetes that have been linked to heightened inflammation caused by an aging immune system.

“This was very exciting to me because we know that aging has a profound and persistent effect on T cells and that these changes can affect brain function in the hippocampus,” said Rosi. “At the moment, this is just an interesting observation, but it gives us a very exciting set of biological puzzles to solve.

ISRIB May Have Wide-Ranging Implications for Neurological Disease

It turns out that chronic ISR activation and resulting blockage of cellular protein production may play a role in a surprisingly wide array of neurological conditions. Below is a partial list of these conditions, based on a recent review by Walter and colleague Mauro Costa-Mattioli of Baylor College of Medicine, which could potentially be treated with an ISR-resetting agent like ISRIB: 

  • Frontotemporal Dementia
  • Alzheimer’s Disease
  • Amyotrophic Lateral Sclerosis (ALS)
  • Age-related Cognitive Decline
  • Multiple Sclerosis
  • Traumatic Brain Injury
  • Parkinson’s Disease
  • Down Syndrome
  • Vanishing White Matter Disorder
  • Prion Disease

ISRIB has been licensed by Calico, a South San Francisco, Calif. company exploring the biology of aging, and the idea of targeting the ISR to treat disease has been picked up by other pharmaceutical companies, Walter says.

One might think that interfering with the ISR, a critical cellular safety mechanism, would be sure to have serious side effects, but so far in all their studies, the researchers have observed none. This is likely due to two factors, Walter says. First, it takes just a few doses of ISRIB to reset unhealthy, chronic ISR activation back to a healthier state, after which it can still respond normally to problems in individual cells. Second, ISRIB has virtually no effect when applied to cells actively employing the ISR in its most powerful form — against an aggressive viral infection, for example.

Naturally, both of these factors make the molecule much less likely to have negative side effects — and more attractive as a potential therapeutic. According to Walter: “It almost seems too good to be true, but with ISRIB we seem to have hit a sweet spot for manipulating the ISR with an ideal therapeutic window.


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Utah boy who has Down syndrome and autism loses merit badges and his shot at becoming an Eagle Scout because of discriminatory policies, lawsuit says




Logan Blythe




Logan Blythe – a 15 yr old boy with Down Syndrome and autism – is not being allowed to progress as a Boy Scout

Find out more by watching the video below.

For more details of the case check out this recent article




Leave a comment Posted on A to Z of Medical Conditions, Children's health

Hirschsprung’s disease – what are the signs and symptoms of Aganglionosis




Hirschsprung’s disease – what are the signs and symptoms of Aganglionosis

Hirschsprung’s disease – what are the signs and symptoms of Aganglionosis

Introduction

Hirschsprung’s disease is a rare condition that causes poo to become stuck in the bowels. It mainly affects babies and young children.

Normally, the bowel continuously squeezes and relaxes to push poo along, a process controlled by your nervous system.

In Hirschsprung’s disease, the nerves that control this movement are missing from a section at the end of the bowel, which means poo can build up and form a blockage.

This can cause severe constipation, and occasionally lead to a serious bowel infection called enterocolitis if it’s not identified and treated early on.

However, the condition is usually picked up soon after birth and treated with surgery as soon as possible.




 

Symptoms of Hirschsprung’s disease

Symptoms of Hirschsprung’s disease are usually noticeable from soon after a baby is born, although occasionally they’re not obvious until a child is a year or two old.

Signs of the condition in a baby include:

failing to pass meconium within 48 hours – the dark, tar-like poo that healthy babies pass soon after being born

a swollen belly

vomiting green fluid (bile)

Signs in older infants and children include:

a swollen belly and a tummy ache

persistent constipation that doesn’t get better with the usual treatments

not feeding well or gaining much weight

If your child develops a bowel infection (enterocolitis), they may also have a high temperature (fever) and watery, foul-smelling diarrhoea.

When to get medical advice

Visit your GP if your child develops the symptoms described above. Hirschsprung’s disease can be serious if left untreated, so it’s important to get help as soon as possible.

If your GP suspects the condition, they will refer you to hospital for tests to confirm the diagnosis.

How Hirschsprung’s disease is diagnosed

Your child’s tummy will usually be examined and sometimes a rectal examination may be carried out. This is where a doctor or nurse inserts a finger into the back passage (rectum) to feel for abnormalities.

If Hirschsprung’s disease is suspected, an X-ray can be done to show a blockage and bulge in the bowel.

The diagnosis can be confirmed by doing a rectal biopsy, which involves inserting a small instrument into your child’s bottom to remove a tiny sample of the affected bowel.

This is then examined under the microscope to see if the nerve cells are missing.

What causes Hirschsprung’s disease?

The muscles of the bowel are controlled by nerve cells called ganglion cells. In Hirschsprung’s disease, these ganglion cells are missing from a section at the end of bowel, extending up from the anus, the opening in the bottom that poo passes through.

For some reason, the cells didn’t develop in that area when the baby was growing in the womb. It’s not clear why this happens, but it’s not thought to be caused by anything the mother did while she was pregnant.

A number of genes are associated with Hirschsprung’s disease and it does sometimes run in families. If you’ve had a child with it before, you’re more likely to have another child with it.




The condition is occasionally part of a wider genetic condition, such as Down’s syndrome, but most cases aren’t.

Treatments for Hirschsprung’s disease

All children with Hirschsprung’s disease will need surgery.

As they wait for surgery, they may need to:

stop having milk feeds and instead be given fluids directly into a vein

have a tube passed through their nose and into their stomach to drain away any fluid and air collecting in it

have regular bowel washouts, where a thin tube is inserted into their bottom and warm salt water is used to soften and flush out the trapped stools

take antibiotics if they have enterocolitis

Your child may need to stay in hospital during this time, or you may be able to look after them at home. Your doctor will advise you about this.

Surgery

Most children will have the “pull-through” operation, where the affected section of bowel is removed and the remaining healthy sections of bowel are joined together. This will usually be done when they’re around three months old.

If your child isn’t well enough to have this procedure – for example, because they have enterocolitis or a severe blockage – they may have it in two stages.

A few days after birth, the surgeon will divert the bowel through a temporary opening (stoma) made in the tummy. This procedure is called a colostomy formation.

Stools will pass directly out of the opening into a pouch worn on your child’s body until they’re well enough to have another procedure to remove the affected section of bowel, close the opening, and join the healthy sections of bowel together. This is usually done at around three months of age.

These procedures can be done using either:

laparoscopic (keyhole) surgery – this involves inserting surgical instruments through tiny cuts

open surgery – where a larger cut is made in your child’s tummy

Speak to your surgeon about the best option for your child.

Risks of surgery

No surgery is risk-free. There’s a small chance of:

bleeding during or after the operation

the bowel becoming infected (enterocolitis)

bowel contents leaking into the body, which could lead to serious infection (peritonitis) if not treated quickly

the bowel becoming narrowed or blocked again, requiring further surgery

Recovery from surgery

Your child will probably need to stay in hospital for a few days after surgery. They’ll be given pain-relieving medicine to make them comfortable and fluids into a vein until they can manage food.

No special diet is needed once you get home, but it’s important they drink plenty of fluids as they recover.

Your child should recover well and their bowels should function normally after surgery.

At first they’ll probably have a sore bottom when they poo. It can help to leave their bottom open to the air whenever possible, and use baby oil to gently clean their bottom as well as nappy cream after each change.

Call your doctor immediately if your child develops problems such as a swollen belly, fever, or foul-smelling diarrhoea.

Outlook for Hirschsprung’s disease

Most children are able to pass stools normally and have a normal functioning bowel after surgery, although they may take a bit longer to toilet train.

Some may experience persistent constipation and need to follow a high-fibre diet and take laxatives. Your doctor will advise about this treatment.

A small number of children have problems controlling their bowels (bowel incontinence), which can last until they’re a teenager and be very distressing.

Speak to your GP if this is a problem. You can also read advice about soiling in children.

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Autism and Down Syndrome: Self-Awareness Series – Find out more about these important books by Michelle Lucci

Ms Lucci and her brother

Ms Lucci and her brother

My name is Michelle Lucci, and I am a sibling of someone with special needs.  My brother, Tony, has Down Syndrome, and he inspired me to become a special education teacher.  I earned my bachelor’s degree from Franciscan University as an Intervention Specialist and my master’s degree from West Virginia University in Multiple and Severe Disabilities. I taught middle school students with special needs for five years before my health forced me to retire.  Now I use my skills and education to write textbooks and make educational materials for students with significant disabilities.

The Self-Awareness Series are books written to start a conversation between an adult and an individual with special needs. The books are written as clearly and gently as possible to promote positive self-esteem, as well as self-acceptance and awareness of weaknesses. They can also be used in special education classrooms for learning how to use reference books.

Growing up, my parents didn’t talk to my brother Tony about his disability. As a result of my education and experience teaching, I realized it would benefit my brother if my parents were to talk to him about his disability. I encouraged my parents to do so, but they were not sure why we should tell him he has Down Syndrome if he isn’t aware.

Think about it this way. Let’s say you have trouble doing something. If you understand why it is challenging for you, you can identify and label the weakness, and as a result, you can strengthen it by finding solutions that help you adapt. For example, I struggle with spelling. Because I have identified that weaknesses, I have found solutions to adapt. I use spell check, ask Siri to spell words for me, and when in doubt, I use a synonym.

Ms Lucci's book on autism

Ms Lucci’s book on autism

Our loved ones often attend their IEP meetings at school as quiet guests and don’t really understand what is going on or why they are there.  If they understand their disability and their weaknesses, they can understand why the adults in their life are working on a plan to help them be successful in school.

Knowledge is power. It is important for our loved ones to have awareness of their own disabilities.  If they are able to identify and understand their weaknesses, then it promotes control over their lives and positive self-esteem.  If they understand why they are different and that there is a reason for why they are the way they are, then they can focus on their strengths, talents, and what makes them special!

The books are available on Kindle. http://www.amazon.com/s/ref=sr_nr_seeall_3?rh=k%3AMichelle+Lucci%2Ci%3Adigital-text&keywords=Michelle+Lucci&ie=UTF8&qid=1461083241

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Improving Social Skills: How to Raise a Socially Intelligent Child




How well your children use social skills, determines how well they function in society. Raising social intelligence lets kids interact with friends, family, and teachers. By knowing how to communicate and behave around others, they can connect with people. And all kids deserve the same chance at achieving social happiness. Kids with Autism Spectrum Disorder (ASD), Down syndrome, Social Anxiety, Attention Deficit Disorder (ADD), just need a little bit more patience.

Teach your kids to treat others, the same way they would want others to treat them. When kids adopt positive social values, people will feel good around them. To achieve this, be smart about how you teach your kids to be social intelligent.




Improving Social Skills: How to Raise a Socially Intelligent Child

Improving Social Skills: How to Raise a Socially Intelligent Child

During childhood, kids look to parents for guidance. But, what kids never tell you is they also observe your every action, and learn from it. How you conduct yourself in everyday situations can influence your child’s social intelligence. Teaching kids social skills can be as simple as being well-mannered yourself. By being exposed to this, kids will reflect your character traits as their own. They will become thoughtful, respectful, and polite to others. It is also important to express those values when interacting with your child. This is especially true for kids suffering from autism and social anxiety. By exposing them to constructive behavior, kids will learn to overcome personal setbacks with positive social values.




Play to Learn

Improving Social Skills: How to Raise a Socially Intelligent Child

Improving Social Skills: How to Raise a Socially Intelligent Child

Play games to help your kids develop complex social skills. This can be a great informal learning method, which can benefit kids’ with ADD. A familiar activity can help with abstract notions of personal space, and non-verbal communication. Role playing is a great way of teaching kids how to act in various situations. They will become socially polite, and learn how to read body language. Create cue cards, to help kids learn how to read facial expressions through reenactment. While kids with autism and social phobia can practice maintaining eye-contact with a simple staring game.

Communication

How well you communicate with your child, reflects how well they interact with others. Use positive reinforcement, to encourage kids to engage in conversation. This reflects your affection and interest, teaching them to be comfortable when expressing ideas. You should also listen to your kids when they talk. Knowing to contribute to a conversation, will create an air of confidence around them. But, they need to listen as well. This can be hard for children with Down syndrome and ADD. So, let them initiate the conversation, and then speak your mind to keep their focus. When addressing bad behavior, always use assertiveness to convey your point. Assertive communication will divert their actions from bad to good, without bruising their self-confidence. And when they learn to use it, they will be able to successfully manage conflict situations.

Throw a Party

Parties play a significant role in rewarding children’s milestone achievements.

Autism

Autism

But, they also provide the perfect opportunity for improving social skills. Children have a chance to practice what they have learned, while having fun with friends. Parties are also the perfect place to meet people, and create new friendships. With everyone celebrating your child, parties can also boost their self-confidence in public appearances. Thus, parties can have a positive effect on children suffering from autism, depression, and social anxiety.  Arrange a costumed superhero party as a way of overcoming psychological barriers. By adopting the role of their favorite superhero, socially impaired kids can neutralize differences, and defeat their fears.

Take a Step Back

 Taking a step back may be hard, but sometimes it is the only way your children can learn. Letting kids experience social interaction first hand allows them to discover how things work. They will rely on themselves to experiment, refine, and implement the skills they gained. It will be a chance to build their self-image, and find ways to connect with people. They will learn to overcome the fear of rejection, and to cope with setbacks. A thicker skin will let them search for social acceptance, and affection they receive from you. And when they realize their full potential, kids can achieve social happiness.

In learning to accept themselves, they can overcome any personal difficulty. Using social skills intelligently, will allow them to find people who appreciate them. In doing so, they can achieve love, happiness, and friendship throughout their life.

About author:

Tracey Clayton is a full time mom of three girls. She loves cooking, baking, sewing, spending quality time with her daughters and she’s passionate for writing. Her motto is: “Live the life you love, love the life you live.”