- 1 SMA type 1
- 1.1 SMA type 1 – first signs in kids
- 1.2 Spinal Muscular atrophy statistics
- 1.3 SMA type 1/ Werdnig-Hoffman disease observations
- 1.4 SMA type1 / Werdnig-Hoffman disease symptoms
- 1.5 SMA type 1/ Werdnig-Hoffman disease Diagnosis
- 1.6 SMA type 1 treatment
- 1.7 SMA type 1 / Werdnig-Hoffman disease Physiotherapy and occupational therapy
- 1.8 SMA type 1 / Werdnig-Hoffman disease Diagnosis
- 1.9 SMA type 1 Prognosis
- 1.10 Spinal Muscular atrophy – SMN2 gene
- 1.11 Werdnig-Hoffman disease – Motor neuron protection
- 1.12 Werdnig-Hoffman disease – Ongoing examinations for new treatments
- 1.13 Werdnig-Hoffman disease – Stem cells therapy
- 1.14 Werdnig-Hoffman disease – Research challenges
- 1.15 Werdnig-Hoffman disease gene carriers
- 1.16 Finding more on Werdnig-Hoffman disease
SMA type 1
is an uncommon severe genetic disease of muscles in babies resulting due to genetic defect in parents. It is an aggressive muscle weakening disorder with high mortality rate.
Spinal Cord contains a large portion of motor neurons. The motor neurons bring about the muscle movement in the body.
The motor neurons stop functioning effectively.
This results in a genetic muscular disorder called Spinal Muscular atrophy (SMA).
The muscles start getting weak. The medical term for such a syndrome is “Atrophy” Hence the name Spinal Muscle Atrophy
The age, signs and speed of development of SMA depends on the type. It has been categorized into four types. These are SMA type 1, 2, 3 and SMA type 4. They are classified ino these types based on age when first signs od SMA start appearing..
Read here about muscle atrophy in general..
SMA type 1 – first signs in kids
The age, signs and speed of development of depends on the type. It has been categorized into four types. That will be corresponding to which physical milestone has been reached in the patient.
Amongst all the Spinal Muscular atrophy types, SMA type 1 or Werdnig-Hoffman disease is the worst one. Since it affects the muscles, the kids born with this disease are unable to even sit properly on their own without any external support. Most of the babies may not even celebrate their second birthday. Surprisingly these babies have no problem about intellect. Most of them are quite lively, smiling and alert.
Spinal Muscular atrophy statistics
: Out of every 6000 babies that are newly born, one is likely to be affected by Spinal Muscular atrophy. And in that, from among every 40 people, one could be expected to be a Genetic Carrier. Of all the four types of Spinal Muscular atrophy, the one occurring most in people is Werdnig-Hoffman disease or SMA type 1
SMA type 1/ Werdnig-Hoffman disease observations
– The first thing that anyone would like to know is the SMA type 1 symptoms.
-Also What is the basic cause of SMA type 1/ Werdnig-Hoffman disease ?
-What steps should be taken to ascertain or diagnose SMA type 1 ?
-What is the prognosis of SMA type 1 ?
-How active is the research community on SMA type 1 / Werdnig-Hoffman disease ?
-What are the latest findings ?
-If someone is carrying gene related to SMA type 1/ Werdnig-Hoffman disease, what action should he take?
SMA type1 / Werdnig-Hoffman disease symptoms
No strength in muscles and weak tone of muscles
• Muscle weakness and poor muscle tone
• Head Control not good
• Cough and cry very debilitating
• Strength of the legs worse than the arms
• Lot of strain and pain when feeding or swallowing
• Likelihood of infections to Respiratory tract very high.
• Sitting properly without support or lifting the head becomes very difficult.
SMA type 1/ Werdnig-Hoffman disease Diagnosis
The age of diagnosis is generally prior to five to six months. Mostly even three month sometimes. Some mothers have even mentioned that they found very little movement of baby in the final months of pregnancy. As a sign of Werdnig-Hoffman disease , the babies show very poor development in all aspects related to use of muscles. Walking, sitting up without help, crawling, holding up the head or even rolling over is difficult for such babies. The muscles of neck, upper arms and legs are the weakest. They may be seen to have slightly concave type body structure with prominent belly and very thin at the top. The diaphragm muscles are good and hence such babies are seen to breathe through their stomach.. It’s important to note that Spinal Muscular atrophy affects all the vital muscles such as food digestion, sucking, excreting and swallowing.
The life expectancy of a baby with Werdnig-Hoffman disease would depend on when the disease starts showing the symptoms. Shorter life span is seen when the symptoms start showing very early in Life.
SMA type 1 treatment
Unfortunately there isn’t a perfect cure for SMA type 1. It is sadly a disorder of fatal type. The research to deal with this disease has gained a lot of momentum. It is highlighted in the relevant section below. The quality of life of the patient can be improved nevertheless. There are a lot of things that can be done to help the family and child.
The Medical team to handle such cases would comprise of diverse specialists and not just expert of one type. Since there would be multiple specialists from various fields, a care coordinator would play an important role to coordinate all the activity. The group of specialists could include experts from Occupational therapy, respiratory medicine, genetics, speech and language therapy, physiotherapy, palliative care and even gastrointestinal /dietetics. All in all, it would be not an easy task to coordinate for the coordinator. But the nature of disease necessitates the same.
SMA type 1 / Werdnig-Hoffman disease Physiotherapy and occupational therapy
Some of the exercises that a physiotherapist assigns such patients are of passive nature. They may include movements which are difficult for the babies or children to make them by themselves. Some of the babies could like such movements. These exercises in Spinal Muscular Atrophy could be good for blood circulation and avoiding joints stiffening. The most important exercises are those that enhance Respiration. There is also something called Physiotherapy for chest done by slowly clapping on chest to clear off the lungs of too much mucus and thereby also helping in softening of secretions. These aids the babies particularly when the babies have tough time in coughing. They can also assist in decreasing the severity of infections of chest.
SMA type 1 – emotional aspect for babies.
For SMA type 1, the cognitive, emotional and physical aspect of the babies can also be stimulated. Feathers and balloons could be used for this. They could give a feeling of freedom and energy to them. The physiotherapist or occupational therapist could even recommend some different seating methods or systems that the child is happy and move its body very easily.
Since babies like to play in water very much, hydrotherapy could be extremely good for them. They just enjoy the touch and sight of flowing water. Care should be taken however to ensure that water is not swallowed creating further complications.
SMA type 1 – Eliminating mucus
Often times babies suffering with Spinal muscular atrophy face problems eliminating mucus from the far end of their throats. In such cases, suction machine should be made available for them. The suction pump mechanism has a thin plastic tube going behind the mouth to suck out all the mucous that has collected there. Even minor coughing helps to clear such mucus. There are devices named “CoughAssist” for this purpose.
SMA type 1/ Werdnig-Hoffman disease- treating respiratory problems
If the babies suffering with Werdnig-Hoffman disease / SMA type 1 have weak respiratory muscles, than surely they need help with breathing. Experts and members from medical assist team will conduct their own tests to check the breathing and decide if some kind of intervention is really needed. Modern devices which are portable and effective can be use to improve the conditions of babies in such cases. SMA type 1 / Werdnig-Hoffman disease babies generally need support for breathing during the sleep. Some may need more support at least when suffering from colds. The Doctors will advise on the proper ventilator to use for same
Illness and fever needs to be treated with proper plan. Small respiratory system related fevers could be quite problematic for babies with Spinal muscular atrophy. Special or Expert medical assistance should be possible on urgent basis during such times. Influenza vaccine along with other normal immunizations are very helpful.
SMA type 1 – Swallowing problems for babies
Babies with SMA type 1 could also face problems of swallowing. There could be even risks related to choking because of this. A feeding tube is recommended in such cases. The related options are something like these:
A tube from nose that reaches the stomach directly called as NG tube or Nasogatric tube. This is normally used for short term use only as the feeling is found to be quite uncomfortable for patient.
A tube going from the skin directly to stomach called as G tube or Gastrotomy tube. This tube is place in the body with surgery.
Such kind of interventions are not always easy or comfortable for patients with or even in general. They do cause some minor pain and inconvenience till the time they are used. But they many become important to enhance the baby’s overall condition. At the same time, one definitely needs to know the facts and rights before taking any such decisions related to interventions. The parents should discuss the matter thoroughly among themselves as it could be tough decision sometimes. The sight of their cute baby with tubular interventions is never a good thing for parents to watch. All the options should be discussed with the counselor too.
After finalizing the decision, one will need to write and authorize the interventions indicating permissions to the medical personnel.
SMA type 1 / Werdnig-Hoffman disease Causes
is triggered by abnormalities affecting the “survival motor neuron 1” (SMN1) gene, which is a part of the fifth chromosome. These genetic defects have to be inherited by both parents in order for one to be born with the disease. This is known as autosomal recessive inheritance.
If someone is born with this Disease, then both their parents carry the defective genes. However they both probably only have one ‘bad’ copy of the gene, which makes them ‘carriers’ and thus they show no symptoms in most cases. The normal copy of the gene works well enough to keep their motor neurons in check and allow them to function properly. For a child to be affected by the condition, both parents have to be carriers and both have to pass on the faulty genes. With both parents having one good and one bad copy of the gene, the odds of that happening are 25%. Statistically speaking, 1 in 40 people carry the defective SMN1 genes that can potentially result in a child suffering from
The alterations of the SMN1 gene result in it not being able to function properly; the gene is either copied incorrectly, or missing altogether. The SMN1 gene is responsible for the instructions of the production of survival motor neuron protein (SMN), which is crucial for the survival of motor neurons. Motor neurons cannot function properly without it, which is why they can’t survive if the protein is found in insufficient amounts in the body. The role of motor neurons in the body is to convey signals from the spinal cord (where they are located), to the muscles, thus controlling their functions.
It is possible to suffer from and be less symptomatic, which is observed in some people. One of the reasons is the activity of a gene called SMN2. This gene also has a role in the production of variations of the SMN protein, though in much smaller amounts than SMN1 when it comes to the complete version of the protein. However, some people have more copies of the gene, which manages to somewhat compensate for the inaptitude of SMN1 to code the production of enough SMN protein and slow down the disease’s progression, thus reducing symptoms. Generally speaking, people who suffer from SMA type 1 Disease have a single copy of the SMN2 gene, two at most, which is not enough to compensate even a little for the absence of a properly working SMN1 gene. That being said, if a person has more than two copies of the SMN2 gene, as is the case in types 2 through 4, then the production of SMN protein is enough to abate the course of the disease and decrease symptoms.
The condition may also be affected by the production of other proteins that are present in the human body. These proteins modify the disease and its course. So far, only ‘plastin 3’ and ‘ZPR1’ have been discovered in relation to SMA type 1 Disease. If a person who suffers from , produces higher levels of these proteins, their symptoms are less prominent, but one needs to study this further in order to find out the particular mechanisms that affect the outcome.
SMA type 1 / Werdnig-Hoffman disease Diagnosis
The diagnosis for SMA type 1 is usually done on babies before they are six months of age. In case a baby is symptomatic and further examination points toward SMA (Spinal Muscular atrophy), then a blood test is done in order to figure out if the SMN1 gene is there or not. In most cases, the condition is characterized by lack of the gene altogether (this is in about 95% of the cases).
In cases where the gene is present as pointed out by the test, detailed physical examination is done in order to figure out if there are indications of alterations in other genes that can also trigger the condition.
Other tests in a laboratory required for setting may also be employed in order to rule out possibilities of other neuromuscular diseases:
• Electromyography (EMG) is a test that makes measurements of the activity in the muscles from an electrical perspective. Miniature electrodes in the form of needles are placed in the muscles and patterns are being recorded, and then examined.
• Nerve conduction velocity test (NCV) helps establish the nerves’ reactivity to stimuli. This is determined through the administration of small electric charges in order to figure out if nerves work properly.
• Blood test looking for a muscle enzyme called ‘creatine kinase’– a positive result may point out to Spinal Muscular dystrophy.
• In some cases, even muscle biopsy may be requested.
In the cases where these test point out to , genetic tests relating to the SMN1 is needed. In a small percent of cases (about 5%), the SMN1 gene is not completely absent, but is somehow defective, which makes it inept to perform its functions. Looking for these alterations is much more difficult than figuring out if the gene is there or not, so the results of such tests usually take more time.
SMA type 1 Prognosis
SMA type 1 has bad prognoses as of now, as most babies affected by the disease don’t make it past three years, and many pass away during the first. Generally speaking, it’s better if the symptoms don’t show early in age. If the symptoms start showing at a higher age, prognosis can be better. But most experts dislike making predictions due to the uncertain course of the disease.
Because of the symptomatic variety and level of severity of the disease, it is rather important to understand the individual needs of the patients. It is of prime importance to cater care plans and treatments to those needs, and try not to broaden them in any way.
Best case scenario for a child that suffers from SMA type 1 is to be found by experts in the field. They can thus meet the child’s needs and compensate for difficulties related to the condition. Family members are obviously an important part of the equation. If they work together with the experts, they can reduce the harshness of the experience for the child significantly.
Werdnig-Hoffman disease does not affect the brain, which means that children will preserve their cognitive abilities. Hence parents should always encourage their children to participate in developmental activities, with adjustments to the process if they are needed.
Werdnig-Hoffman disease / SMA type 1 Research
There are several trials currently being conducted in order to test new treatments for this disease. Though SMA type 1 is still relatively uninvolved in these processes, it is believed that if a treatment is effective for one of the types, then it would probably be effective for other types, as well.
Werdnig-Hoffman disease- Gene Therapy
Goal of Gene therapy for Werdnig-Hoffman disease is to somehow assist in production of SMN proteins in the motor neurons. This is being done by introducing SMN1 gene straight into motor neurons. But this process of introduction is extremely difficult and is supposed to be a monumental challenge until recent years. Some medical expert groups published important reports in 2010 and 2011 in this regards. These showed that a specific virus named AAV9 (Adeno –associated virus type 9) is suitable for sending the SMN1 gene to the motor neurons of mice. The gene was injected directly into their blood stream for this.Gene therapy for Werdnig-Hoffman disease enhanced the life span and overall functioning of motor neurons in the mice.
From June of year 2014, gene therapy clinical trials have already begun in American company Avexis Inc. This trial will be conducted on patients of 9 years of age with Werdnig-Hoffman disease. Further details relating to this clinical trial is accessible on the site clinicaltrials.gov
Spinal Muscular atrophy – SMN2 gene
Many strategies are also trying to check if the SMN2 gene can also be used for the Gene therapy. Like say altering the genetic instructions which are generated by SMN2 gene to produce more quantity of complete SMN protein. Some experts have also gone along the ‘trial and error’ strategy. They tested huge number of molecules to see if any one enhanced the generation of the required SMN protein. Some experts are following a more pin pointed approach too. These are like specifically producing drugs which may change the working of SMN2 gene.
An experimental drug going by the name of RG3039 is perhaps the embodiment of the first method. After testing over half a million possible drugs, scientists in the USA have come across a chemical complex that managed to induce the production of full-length SMN protein derived from the SMN2 gene. The formula of the complex was then adjusted for the production of RG3039. Laboratory experiments involving mice were used to test the compound’s effectiveness. The tests demonstrated that the drug was effective in several areas, including increase in life expectancy and motor neuron survival, and thus decreasing some symptoms caused by the disease in the rodents. Currently, Repligen Corporation is testing the drug in a Phase 1 clinical trial using volunteers unaffected by the disease in order to conclude how safe it is and to define its pharmacokinetics (see glossary below). Researchers hope that the data extracted from this Phase 1 trial will have a positive effect on devising the next series of trials of RG3039 in individuals suffering from Werdnig-Hoffman disease. Pfizer has purchased the rights for RG3039 and will continue research, advancement, and tests in this direction.
Isis Pharmaceuticals are employing a more concrete method and are currently conducting tests using a chemical complex going by the name of ISIS-SMNRx for Spinal Muscular atrophy. The clinical trials are well underway. ISIS-SMNRx is an antisense oligonucleotide (AON), which are compounds that determine the way certain genetic code is interpreted. The idea is to use the AONs to make the SMN2 gene order cells to synthesize more full-length SMN protein. Experiments involving mice have so far shown that the drug has positive effects on the symptoms of the illness, as well as increase in survival rate.
The company has claimed an optimistic outcome as two clinical trials of the drug are underway. One of the trials aims at determining the effectiveness of the drug in children, affected by Werdnig-Hoffman disease , as two doses are being tested. The other one aims at determining the effectiveness of four doses in children suffering from other types of this disease, such as Spinal muscular atrophy type 2 or 3. Currently, results show an optimistic view of the drug’s effectiveness and the children handle it very well.
Current trials for the ISIS-SMNRx are being conducted on a small scale, which means that further testing will be needed in order to determine the true efficiency and safety of the drug. The outcome of the current trials has been good enough for an optimistic prognosis, though. A more large-scale study is already in the works. Follow the link for more information on the ISIS clinical trials.
Werdnig-Hoffman disease – Motor neuron protection
Trophos (now acquired by Roche ) is a French company in the pharmaceutical industry. They are working on a substance that resembles cholesterol and provides protection to the neurons, as well as augments their development and function. It’s called Olesoxime and may very well prove effective in slowing down Werdnig-Hoffman disease.
The drug proved quite effective in two trials. The Phase 1 trial proved a success, which made the company launch a second one, but this time on a bigger scale. It involved 165 patients ages varying from three to 25 years old, all of them suffering from Spinal muscular atrophy types 2 and 3. Results were published in March 2014. Olesoxime proved to prevent motor function loss in patients as compared to the placebo group. The subjects taking the drug also showed much lesser complications that typically accompany the illness, such as respiratory infections. Trophos (Roche) has also determined that Olesoxime is safe and are planning to apply for approval in both Europe and the US as soon as they can.
Werdnig-Hoffman disease – Ongoing examinations for new treatments
Pharmaceutical companies and research institutions alike are trying to discover new treatments for this disease. Such companies are Merck, PTC Therapeutics, and Novartis. PTC Therapeutics are heavily working on a potential treatment for SMA or Spinal Muscular Atrophy.
Werdnig-Hoffman disease – Stem cells therapy
Stem cell research is another interesting possibility for treating this disease. The idea is to use stem cells to directly substitute the dead motor neurons. This method has been shown effective in mice, both in terms of mobility and survivability. There are still many unknowns which current studies are trying to determine in order to execute this method in the most efficient manner. California Stem Cell Inc. is among the most active in this field of study.
Werdnig-Hoffman disease – Research challenges
Providing the evidence that a therapeutic method works is among the biggest challenges relating to Werdnig-Hoffman disease treatment research. There is a high degree of variability in symptoms in different patients, which makes measuring the actual effectiveness of a drug rather difficult. SMA (Spinal Muscular atrophy) types 2 and 3 work relatively slowly, which means that detecting potential positive change becomes even harder. As for , children suffering the condition are in many cases too weak with fever to participate in some of the tests.
Proper timing is also quite important for the effectiveness of the therapy. However, it is difficult to design proper clinical trials with optimistic prognoses because there is still so much unknown about the condition. In case of a breakthrough, it would be best for it to be implemented in new-borns as soon as possible before the damage to the motor neurons is done.
Werdnig-Hoffman disease gene carriers
In case one carries the Werdnig-Hoffman disease gene, it would be a good idea to discuss with a genetic counselor. In case you are already taking care of a child with Werdnig-Hoffman disease , then the counselor can advise you on different options which you could bear in mind for pregnancies in future.
Preimplantation genetic diagnosis (PGD) is a great method considered by many couples that carry the SMA type 1 gene. Eggs are being fertilised in a controlled setting where the resulting embryos are then being tested for the condition. Only embryos that do not display the mutation are implanted back in the womb.
Something else that might be considered is called prenatal diagnosis – the fetus of a pregnant woman is tested, and the couple gets to decide whether they want to keep it or not if it is diagnosed with Spinal muscular atrophy.
Finally, using sperm or egg donors, or adopting a child are also great options for some couples.
Finding more on Werdnig-Hoffman disease
- Fight SMA/Spinal Muscular Atrophy
- Jennifer Trust for Spinal Muscular Atrophy
- Cure SMA
- Child Neurology Foundation
- 1321 Duke Street
- Suite 104
- Alexandria, VA 22314
- Phone #: 703-299-1144
- 800 #: N/A
- e-mail: CarolineGibson@fightsma.com
- Web site: www.fightsma.org
- 40 Cygnet Court
- Timothy’s Bridge Road
- Stratford upon Avon
- Warwickshire, CV37 9NW United Kingdom
- Phone #: 440-178-9267520
- 800 #: 800-975-3100
- e-mail: firstname.lastname@example.org
- Web site: http://www.jtsma.org.uk
- 925 Busse Road
- Elk Grove Village, IL 60007
- Phone #: 847-367-7620
- 800 #: 800-886-1762
- e-mail: info@cureSMA.org
- Web site: www.cureSMA.org
- 201 Chicago Ave, #200
- Minneapolis, MN 55415 USA
- Phone #: 952-641-6100
- 800 #: 877-263-5430
- e-mail: email@example.com
- Web site: www.childneurologyfoundation.org
Another place to go for Research on Spinal Muscular Atrophy / Werdnig-Hoffman disease is www.fsma.org/research
• A Family Guide to the Standards of Care for Spinal Muscular Atrophy is available in two different formats and 16 different languages