SMN1 SMN2 SMN1 SMN2 DNA - roche.comf1f1f75c-19cc-4455-921a-b4d1ab72b0bb/J4154 SMA... · Spinal...
1
Spinal muscular atrophy (SMA) affects approximately... 1 in 11,000 live births worldwide 1 SMN1 SMA is caused by a mutation in the SMN1 gene, which results in low levels of survival of motor neuron (SMN) protein. SMN protein is found throughout the body and plays a vital role in muscle function 2 The development of SPINAL MUSCULAR ATROPHY Having low levels of functional SMN protein leads to progressive weakening and wastage of nerve cells, which control muscle movement Functional SMN protein Mostly non- functional SMN protein SMN1 SMN2 SMN1 SMN2 DNA Protein No functional SMN protein risk that the child will have SMA chance that the child will also be a carrier chance the child will be completely unaffected 4 A carrier is someone who does not have SMA, they have one ‘normal’ copy of the SMN1 gene and one copy of the SMN1 gene with a mutation 4 Carriers are usually unaware of the mutated gene 4 When two people who are carriers of the affected gene have a child, there is: 4 ...there are produces all the SMN protein we need to function The body has two very similar genes that make SMN protein: SMN2 2 only makes a small fraction of the SMN protein we need to function (about 10%) Healthy individuals The SMN1 gene is able to produce enough protein for the body to function normally Individuals with SMA Must rely on the ‘back up’ SMN2 gene, which produces insufficient amounts of functional SMN protein 2 25% 50% 25% SMA is a whole-body disease, with muscles and other organs throughout the body being affected Although SMA is mainly diagnosed in childhood it can affect people at any age, from childhood to adulthood. However, the earlier symptoms appear, the more severe the disease. 2,8 3 main types of SMA, based on the age when symptoms first appear Babies are often ‘floppy’ due to severe muscle weakness, they struggle to control their head or lift their arms and legs They may also struggle to breath sufficiently on their own Babies will never be able to sit unaided Children with SMA Type 2 will never be able to walk As muscles weaken over time, some people may develop a curvature of the spine, called scoliosis Many will develop significant respiratory and breathing problems, as well as having problems swallowing Many achieve the ability to sit, but this ability will be lost over time People may experience muscle weakness that will get worse over time Many children with Type 3 SMA will learn to walk, but this ability will be lost over time as they progress in to adolescence Life expectancy is not usually affected Legs may be weaker than arms Develops in babies less than 6 months old and is life-limiting. 2,5 Few children survive beyond two years of age Type 1 Type 2 Develops in children who are 7-18 months old, leading to muscle weakness. It may also shorten life expectancy 2,6 Type 3 Develops after 18 months of age and may not be evident until late childhood 2,7 Ongoing research is exploring how other cells and organs, including the... ...may also be affected by low levels of functional SMN protein 9 Heart Vascular system 1. Belter L et al. Journal of Neuromuscular Diseases 5, 2018;167–176 2. Bowerman et al. Disease Models & Mechanisms, 2017;(10):943-954 3. Verhaart I, et al. Orphanet J Rare Dis. 2017; 12:124 4. Cure SMA. About SMA. Available at: www.curesma.org/sma/about-sma/. Last accessed: March 2019. 5. SMA Europe. Type 1. Available at: www.sma-europe.eu/essentials/ spinal-muscular-atrophy-sma/type- 1/. Last accessed: March 2019. 6. SMA Europe. Type 2. Available at: www.sma-europe.eu/essentials/ spinal-muscular-atrophy-sma/type- 2/. Last accessed: March 2019. 7. SMA Europe. About SMA. Available at: www.sma-europe.eu/essentials/. Last accessed: March 2019. 8. SMA Europe. Type 3. Available at: www.sma-europe.eu/essentials/ spinal-muscular-atrophy-sma/type- 3/. Last accessed: March 2019 9. Simone et al. Cell Mol Life Sci. 2016; 73(5): 1003–1020 Mostly non- functional SMN protein Typically diagnosed in childhood, it is the most common genetic cause of death in infants 2 Every person with SMA is different, but... 1 in 45 people is a carrier 3
Transcript of SMN1 SMN2 SMN1 SMN2 DNA - roche.comf1f1f75c-19cc-4455-921a-b4d1ab72b0bb/J4154 SMA... · Spinal...
Spinal muscular atrophy (SMA) affects approximately...
1 in 11,000live births
worldwide1
SMN1
SMA is caused by a mutation in the SMN1 gene, which results in low levels of survival of motor neuron (SMN) protein. SMN protein is found throughout the body and plays a vital role in muscle function2
The development of
SPINAL MUSCULAR ATROPHY
Having low levels of functional SMN protein leads to progressive weakening and wastage of nerve cells, which control muscle movement
Functional SMN protein
Mostly non-functional
SMN protein
SMN1 SMN2 SMN1 SMN2DNA
Protein
No functional SMN protein
risk that the child will have SMA
chance that the child will also be a carrier
chance the child will be completely unaffected4
A carrier is someone who does not have SMA, they have one ‘normal’ copy of the SMN1 gene and one copy of the SMN1 gene with a mutation4
Carriers are usually unaware of the mutated gene4
When two people who are carriers of the affected gene have a child, there is:4
...there are
produces all the SMN protein we need to function
The body has two very similar genes that make SMN protein:
SMN22
only makes a small fraction of the SMN protein we need to function (about 10%)
Healthy individualsThe SMN1 gene is able to produce enough protein for the body to
function normally
Individuals with SMAMust rely on the ‘back up’ SMN2 gene,
which produces insufficient amounts of functional SMN protein2
25%
50%
25%
SMA is a whole-body disease, with muscles and other organs throughout the body being affected
Although SMA is mainly diagnosed in childhood it can affect people at any age, from childhood to adulthood. However, the earlier symptoms appear, the more severe the disease.2,8
3 main types of SMA, based on the age when symptoms first appear
Babies are often ‘floppy’ due to severe muscle weakness, they struggle to control their head or lift their arms and legs
They may also struggle to breath sufficiently on their own
Babies will never be able to sit unaided
Children with SMA Type 2 will never be able to walk
As muscles weaken over time, some people may develop a curvature of the spine, called scoliosis
Many will develop significant respiratory and breathing problems, as well as having problems swallowing
Many achieve the ability to sit, but this ability will be lost over time
People may experience muscle weakness that will get worse over time
Many children with Type 3 SMA will learn to walk, but this ability will be lost over time as they progress in to adolescence
Life expectancy is not usually affected
Legs may be weaker than arms
Develops in babies less than 6 months old and is life-limiting.2,5
Few children survive beyond two years of age
Type1
Type 2Develops in children who are 7-18 months old, leading to muscle weakness. It may also shorten life expectancy2,6
Type 3Develops after 18 months of age and may not be evident until late childhood2,7
Ongoing research is exploring how other cells and organs, including the...
...may also be affected by low levels of functional SMN protein9
Heart
Vascular system
1. Belter L et al. Journal of Neuromuscular Diseases 5, 2018;167–176
2. Bowerman et al. Disease Models & Mechanisms, 2017;(10):943-954
3. Verhaart I, et al. Orphanet J Rare Dis. 2017; 12:124
4. Cure SMA. About SMA. Available at: www.curesma.org/sma/about-sma/. Last accessed: March 2019.
5. SMA Europe. Type 1. Available at: www.sma-europe.eu/essentials/spinal-muscular-atrophy-sma/type-1/. Last accessed: March 2019.
6. SMA Europe. Type 2. Available at: www.sma-europe.eu/essentials/spinal-muscular-atrophy-sma/type-2/. Last accessed: March 2019.
7. SMA Europe. About SMA. Available at: www.sma-europe.eu/essentials/. Last accessed: March 2019.
8. SMA Europe. Type 3. Available at: www.sma-europe.eu/essentials/spinal-muscular-atrophy-sma/type-3/. Last accessed: March 2019
9. Simone et al. Cell Mol Life Sci. 2016; 73(5): 1003–1020
Mostly non-functional
SMN protein
Typically diagnosed in childhood, it is the most common genetic cause of death in infants2
Every person with SMA is different, but...
1 in 45 people is a carrier3
