“The research picture has brightened considerably in the last decade for people with chromosome 5-related spinal muscular atrophy (SMA) types 0 through 4.

Research Trials for SMA leading to actual care for SMA:

The research picture has brightened considerably in the last decade for people with chromosome 5-related spinal muscular atrophy (SMA) types 0 through 4.

Since 1995, scientists have known that a deficiency of functional SMN protein (SMN stands for survival of motor neuron) is the underlying cause of chromosome 5 SMA. Two nearly identical genes carry the genetic instructions for making SMN protein: SMN1 and SMN2. Proteins made from the SMN1 gene are full-length, functional, and appear to be necessary for the survival and proper function of motor neurons. By contrast, proteins made using instructions from the SMN2 gene are shorter and tend to be less stable but can compensate for a lack of SMN protein when the SMN1 gene is not functioning.

In SMA types 0 through  4, flaws (mutations) in each of the two copies of the SMN1 genes result in insufficient production of full-length, functional SMN protein. Fortunately, a certain amount of full-length SMN protein can be made from the SMN2 gene. Many people have multiple copies of the SMN2 gene. These extra SMN2 copies can lessen the impact of a flaw in both SMN1 copies. In chromosome 5-related SMA, the more copies of SMN2 a person has, the milder the course of SMA is likely to be.

Researchers are seeking to exploit this unique redundancy through development of strategies that restore levels of full-length SMN protein.

1- Nusinersen is a drug that has been shown to increase the survival of motor neurons that die off in SMA, robbing children of muscle control. The drug compensates for the effects of the SMN1 mutation by rallying a “backup” gene, known as SMN2. SMN2, like SMN1, also makes the SMN protein needed to keep motor neurons healthy, but most of it is truncated and nonfunctional. Nusinersen uses a genetically based technology called antisense oligonucleotide to shore up this backup gene. This enables people to make more of the full-length, functional SMN protein.

2-Risdiplam is an oral drug taken daily that also appears to boost the production of the SMN protein through the SMN2 gene. Our researchers are an essential part of the clinical testing of risdiplam in the FIREFISH and JEWELFISH studies, which both continue to look at the drug’s efficacy and side effects in infants through adults.

The FIREFISH study involves infants age 1 month to 7 months with infantile-onset SMA, the most severe type. The babies receive risdiplam given as an oral drug daily. The drug increases SMN protein in the infants and improves their ability to sit without support. After two years of treatment, the FIREFISH study shows that 59 percent of treated babies were able to sit without support for five seconds, 65 percent maintained upright head control, 29 percent were able to turn over, and 30 percent were able to stand with support or supporting weight.

One-year results from the JEWELFISH study of risdiplam in children with all types of SMA aged 6 months to 60 years and previously treated with other SMA therapies, showed that risdiplam increases SMN protein levels. The drug appears to double SMN levels among patients who were previously treated with nusinerson or Zolgensma, highlighting its potential as an alternative or add-on therapy to those drugs.

3-Gene Therapy Trials:  To learn more about the potential for gene replacement in children with SMA, we have been involved in several clinical studies. The first, the STR1VE trial, studied intravenous administration of the therapy in infants less than 7 months of age with type 1 SMA. This trial, which followed infants until they were 18 months old, provided the data used by the FDA to approve Zolgensma for the treatment of babies under 2 years.

The STRONG study involves intrathecal (inside the spinal canal) administration of the gene therapy for children between the ages of 6 months to 5 years with SMA type 2. STRONG is on an FDA-hold pending evaluation of pre-clinical information.

Treatment for SMA:

As yet, there is no complete cure for SMA. However, the discovery of the genetic cause of SMA has led to the development of several treatment options that affect the genes involved in SMA — a gene replacement therapy called Zolgensma, and two drugs, called nusinersen (Spinraza) and risdiplam (Evyrsdi).

There is no complete cure for SMA. Treatment consists of managing the symptoms and preventing complications.

Medications

• The U.S. Food and Drug Administration (FDA) approved nusinersen (Spinraza™) as the first drug approved to treat children and adults with SMA. The drug is designed to increase production of the SMN protein, which is critical for the maintenance of motor neurons.
• The FDA approved onasemnogene abeparovec-xioi (Zolgensma ™) gene therapy for children less than two years old who have infantile-onset SMA. A safe virus delivers a fully functional human SMN gene to the targeted motor neurons, which in turn improves muscle movement and function and survival.
• The FDA approved the orally-administered drug risdiplam (Evrysdi) to treat patients age two months of age and older with SMA.

Physical therapy, occupational therapy, and rehabilitation may help to improve posture, prevent joint immobility, and slow muscle weakness and atrophy. Stretching and strengthening exercises may help reduce contractures, increase range of motion, and keeps circulation flowing. Some individuals require additional therapy for speech and swallowing difficulties. Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs may be helpful to improve functional independence.

Proper nutrition and calories are essential to maintaining weight and strength, while avoiding prolonged fasting. People who cannot chew or swallow may require insertion of a feeding tube. Non-invasive ventilation at night can improve breathing during sleep, and some individuals also may require assisted ventilation during the day due to muscle weakness in the neck, throat, and chest.

“Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of motor neurons in the anterior horn of the spinal cord and resultant weakness. The most common form of SMA, accounting for 95% of cases, is autosomal recessive proximal SMA associated with mutations in the survival of motor neurons (SMN1) gene.”

National Library of Medicine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860273/)

“Your muscular heart, the main organ in your cardiovascular system, is vital for life. Its parts work together to move blood through your body in a coordinated way. It constantly sends oxygen to your cells and takes away waste. Many conditions can affect this organ and keep it from working well. Your heart contains four muscular sections (4 chambers) that briefly hold blood before moving it. Electrical impulses make your heart beat, moving blood through these chambers. Your brain and nervous system direct your heart’s function. Your heart controls the speed of your heart rate and B/P.  The heart is the main organ of your circulatory system, your heart keeps you alive. It pumps blood throughout your body, bringing oxygen to your cells and tissues. Since your heart plays such a vital role, it’s important to take care of it. Conditions that affect your heart are very common, but you have the power to make changes for a stronger heart especially before heart problems occur.  The key is prevention.”

Cleveland Clinic (https://my.clevelandclinic.org/health/body/21704-heart)

How the heart is structured and functions:

The human heart is a four-chambered muscular organ that are called atriums at the top LA and RA and the bottom ones called ventricles- right ventricle=RV and left ventricle=LV.  The heart is shaped and sized roughly like a man’s closed fist with two-thirds of the mass to the left of midline which is due to the left ventricle works the hardest pumping blood throughout the body so it makes that chamber the most muscular area.  The right side of the heart pumps blood blood returning to the heart that went throughout the body using up most of the oxygen in it that has mainly carbon dioxide in the blood going the the right side chambers.  First the right atrium and than the right ventricle to just the lungs for more oxygen to the lungs that carries mainly oxygenated blood to the left side of the heart first to the left atrium to the left ventricle that pumps that oxygenated blood through out the body to deliver to all tissues oxygen.

Think of the heart as the engine of the body.  Without a engine the car would not work and without a heart the body would die.  Without the lungs the heart and other tissues would not function and die.  A car without a transmission would not engine would not function and the car would die.

Without oxygen our tissues would go through oxygen starvation and the body would die.  A car without oil would die due to oil starvation and you need the car engine to start the car for the transmission to work with oil to be pumped.

Valves of the Heart:

Pumps need a set of valves to keep the fluid flowing in one direction and the heart is no exception. The heart has two types of valves that keep the blood flowing in the correct direction. The valves between the atria and ventricles are called atrioventricular valves (also called cuspid valves), while those at the bases of the large vessels leaving the ventricles are called semilunar valves.

The right atrioventricular valve is the tricuspid valve. The left atrioventricular valve is the bicuspid, or mitral, valve. The valve between the right ventricle and pulmonary trunk is the pulmonary semilunar valve. The valve between the left ventricle and the aorta is the aortic semilunar valve.

When the ventricles contract, atrioventricular valves close to prevent blood from flowing back into the atria. When the ventricles relax, semilunar valves close to prevent blood from flowing back into the ventricles.

What can happen to the heart if it does not function properly:

Congestive heart failure, or heart failure, is a long-term condition in which your heart can’t pump blood well enough to meet your body’s needs. Your heart is still working. But because it can’t handle the amount of blood it should, blood builds up in other parts of your body. Most of the time, it collects in your lungs, legs and feet.

Think of it like a shipping department that can’t keep up with getting all the shipments where they need to go. The shipping department is always running behind and things pile up. When things pile up, they cause issues OR think of it like plumbing if there is a problem with the water getting through the pipe lines (like our blood flow getting through the veins and arteries) you will need a plumber to fix the blockage, valve problem or broken pipe (just like the blood getting through the body due to a blockage in the vein or artery or bad heart valve or failure elsewhere in that system)

Heart Failure or Congested Heart Failure (CHF) there are types Right sided CHF or heart failure or Left sided CHF or heart failure.   Sometimes the MD may even see High output failure but rare.  More than 6 million people in the United States have congestive heart failure. It’s the leading cause of hospitalization in people older than 65.

Some of the complications from congestive heart failure include:

• Irregular heartbeat.
• Sudden cardiac arrest.
• Heart valve problems.
• A collection of fluid in your lungs.
• Pulmonary hypertension.
• Kidney damage.
• Liver damage.
• Malnutrition.

MOST IMPORTANTLY REMEMBER THIS:

There’s no cure for heart failure. As congestive heart failure gets worse, your heart muscle pumps less blood to your organs, and you move toward the next stage of heart failure(there are A,B,C,D stages). Since you can’t move backward through the heart failure stages, the goal of treatment is to keep you from moving forward through the stages at its slowest pace or to slow down the progression of your heart failure with giving you the chance to live as long as possible at your optimal level.

Regarding Heart Valves there is this to know:

Heart valve disease can affect anyone. But people over 65 are at higher risk. In fact, 2.5 million people over the age of 75 have aortic stenosis, one of the most common types of heart valve disease. While its symptoms can be subtle they shouldn’t be brushed off as “getting older.” Left untreated, it can progress to severe aortic stenosis, also known as heart valve failure.

People over 65 y/o are at highest risk for this and that is based on the my theory like a car the older you are the higher the risk your car is going to be worn down just like the heart (the engine to the body) the older it is the higher the risk that individual will have body part problems like the heart.

Symptoms are your body’s way of sending warning signs that you may be in danger. Unfortunately, diet and exercise can’t fix a failing heart valve. Take control by asking for a referral to a Heart Valve Team or Cardiologist so you can be evaluated.

Without treatment, 1 in 10 people with heart valve failure may die within 5 weeksof symptoms starting if they don’t get a recommended valve replacement!

Remember this important note the better you care for the car the longer it lasts and the better you take care of yourself the longer it lasts.

“During hip replacement, a surgeon removes the damaged sections of the hip joint and replaces them with parts usually constructed of metal, ceramic and very hard plastic. This artificial joint (prosthesis) helps reduce pain and improve function.

Also called total hip arthroplasty, hip replacement surgery might be an option if hip pain interferes with daily activities and nonsurgical treatments haven’t helped or are no longer effective. Arthritis damage is the most common reason to need.

Hip replacement may be an option if hip pain:

• Persists, despite pain medication
• Worsens with walking, even with a cane or walker
• Interferes with sleep
• Affects the ability to walk up or down stairs
• Makes it difficult to rise from a seated position”

MAYO CLINIC (https://www.mayoclinic.org/tests-procedures/hip-replacement/about/pac-20385042)

“Indeed, music is a potent tool for the future of precision medicine. As the scientific community continues to elucidate the emotional landscape of music, as well as how it differs from listener to listener, new methods for alleviating disease severity and improving overall well-being await both patients and otherwise healthy members of the general public.

The effect of music on our brains has clinical implications as well. Growing evidence suggests, for example, that listening to Mozart’s Sonata for Two Pianos in D Major can reduce the frequency of seizures in some people with epilepsy.

Identifying the exact type of music able to provoke a particular cognitive, motor, or emotional response, there could be progress toward healing, improving, or compensating for disrupted brain function in various diseases. An increased understanding of brain mechanisms can facilitate this.

David Silbersweig, the Stanley Cobb Professor of Psychiatry at HMS and chair emeritus of the Department of Psychiatry at Brigham and Women’s Hospital, is interested in uncovering answers to these questions. A leader in functional neuroimaging research in psychiatry, he investigates how brain regions and networks function when we perceive, think, feel, and act.

“We seem to be very much tuned for music”

“It’s at the systems level with brain imaging that you can directly correlate mental states and brain states — and measure them.” Silbersweig says. “Neuroimaging provides a noninvasive way of correlating brain structural and functional abnormalities with specific aspects of music processing.”

STRESS

Another factor in music’s ability to reduce pain likely stems from its competition for our attention. “If you’re thinking about something else, then you’re not thinking about your pain, and you feel less pain,” says psychologist David Bradshaw, who studies pain relief at the University of Utah’s Pain Research Center.  Bradshaw’s research shows that the more actively engaged a person is in music, the less pain they feel. For instance, a group of non-musicians asked to listen for errors in a musical passage reported less pain when receiving small electric shocks than those who passively listened to the music. 

Other work out of Bradshaw’s lab suggests that certain personality factors, such as a propensity toward anxiety or the ability to become easily absorbed in activities, may lead individuals to experience greater relief from engaged music listening. These findings suggest that physicians should consider patients’ personalities when recommending pain treatment programs. 

Listening to a song can have a real effect on various parts of the brain, with studies showing that areas responsible for aspects, such as memory and vision, can ‘light up’ in response to music.

“There’s a very wide range of reactions in the body and mind to music, and brain imaging studies have shown that various parts of the brain may be activated by a piece of music.”,  says Dr Victoria Williamson, lecturer in psychology at Goldsmith’s College, London.

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‘For example, a recent study in Canada showed that there’s a real causal relationship between music and the reward system, a core part of the brain that reacts to stimuli, which are good for us – food, light, sex for example – and reinforces these behaviors meaning that we do them more.’

Researchers at McGill University in Montreal showed that listening to pleasurable music of any description induced ‘musical chills’, which triggered the release of the feel-good chemical dopamine.

“We all know from our own individual experiences that listening to music can affect mood”, says Bridget O’Connell, head of information at the mental health charity Mind.

Music may even be able to help you concentrate.

A new ‘digital tonic’ called Ubrain, which can be downloaded onto smartphones, claims to be able to help people focus, energise, wake up as well as relax.

The process uses two different beats in each ear to create a third ‘perceived’ beat (a binaural beat), which can stimulate certain activity in the brain.

“By helping the brain cortex to generate specific brain waves, we can induce different states of alertness, depending on what we aim to do”, explains Paris-based clinical psychologist Brigitte Forgeot.

If we’re feeling anxious or stressed, we can encourage our cerebral cortex to produce slow alpha-frequency brain waves, while on the other end of the scale, if we help our cortex to produce faster beta waves, we will be better equipped to concentrate and focus our attention on a fairly lengthy task.

FOCUS

Music may even be able to help you concentrate.

A new ‘digital tonic’ called Ubrain, which can be downloaded onto smartphones, claims to be able to help people focus, energise, wake up as well as relax.

The process uses two different beats in each ear to create a third ‘perceived’ beat (a binaural beat), which can stimulate certain activity in the brain.

“By helping the brain cortex to generate specific brain waves, we can induce different states of alertness, depending on what we aim to do”, explains Paris-based clinical psychologist Brigitte Forgeot.

If we’re feeling anxious or stressed, we can encourage our cerebral cortex to produce slow alpha-frequency brain waves, while on the other end of the scale, if we help our cortex to produce faster beta waves, we will be better equipped to concentrate and focus our attention on a fairly lengthy task.

PREVENTION OF DISEASE by increasing the immunity through music—AMAZING!

Can listening to music actually help prevent disease? Some researchers think so.

Wilkes University researchers looked at how music affects levels of IgA — an important antibody for our immune system’s first line of defense against disease. Undergraduate students had their salivary IgA levels measured before and after 30 minutes of exposure to one of four conditions — listening to a tone click, a radio broadcast, a tape of soothing music or silence. Those students exposed to the soothing music had significantly greater increases in IgA than any of the other conditions, suggesting that exposure to music (and not other sounds) might improve innate immunity.

Another study from Massachusetts General Hospital found that listening to Mozart’s piano sonatas helped relax critically ill patients by lowering stress hormone levels, but the music also decreased blood levels of interleukin-6 — a protein that has been implicated in higher mortality rates, diabetes and heart problems.

According to a 2013 meta-analysis, authors Mona Lisa Chanda and Daniel Levitin concluded that music has the potential to augment immune response systems, but that the findings to date are preliminary. Still, as Levitin notes in one article on the study, “I think the promise of music as medicine is that it’s natural and it’s cheap and it doesn’t have the unwanted side effects that many pharmaceutical products do.”

FOR THE DISEASED PATIENTS

Music can actually have a significant positive impact on patients with long-term illnesses, such as heart disease, cancer and respiratory conditions (Home, in nursing homes, hospitals, the office, etc…)

Numerous trials have shown that music can help lower heart rate, blood pressure and help relieve pain, anxiety and improve patient quality of life.

“Music can be incredibly useful for somebody who is in a situation where they have lost a lot of control from their external environment – say they are in hospital for a long period of time with a serious illness and less able to move around,” says Dr Williamson.

‘It can give them a sense of control back, as well as creating a calm personal atmosphere and blocking out some of the disturbances around the patient.

According to sports researchers Peter Terry and Costas Karageorghis, “Music has the capacity to capture attention, lift spirits, generate emotion, change or regulate mood, evoke memories, increase work output, reduce inhibitions and encourage rhythmic movement — all of which have potential applications in sport and exercise.”

MUSIC IS AMAZING ON OUR HUMAN BODY REGARDING OUR HEALTH!! WHAT A GREAT MEDICINE!!

“If you want to firm up your body, head to the gym. If you want to exercise your brain, listen to music.