This month has been designated by someone as “SMA Awareness Month”. As someone who has had Spinal Muscular Atrophy or SMA his entire life I don’t think I could be more aware 🙂 I always wonder about people who have breast cancer or who have family members who have had breast cancer if they ask the same question whenever they say it is “Breast Cancer Awareness Month”?

Really?

Is there anybody out there who has never heard of breast cancer?

But seriously folks… Back to the topic at hand. SMA is considerably more obscure. Even if you’ve known me many years you may not know why I’ve been in a wheelchair my whole life. What put me here? What is SMA?

So in the spirit of SMA Awareness Month” I thought I would spread a little knowledge and invite questions.

SMA is a genetic disease. Both my mom and dad were carriers and did not know it. Estimates are that approximately one in 40 to 50 people are carriers. Even if both parents are carriers there is only a one in four chance that each child would have the disease. Of course that’s just a percentage over the long haul. You can flip a coin 10 times, have it always come up heads and the next one is still 50/50.

There are a variety of types of SMA. Type 1 is extremely severe and without intervention those kids are lucky to see their second birthday. With respiratory support, G-tube feeding etc. they can live several years. There are a choice of new treatments that can prolong that. More on that later.

I have Type 2 which is not as severe but it generally means that I never walked (which I did not). Type 3 people can generally walk until their early teens and sometimes later. There is a type 4 which actually is a significantly different disease but is still called SMA and I don’t know much about it. Even within the types there is a great variation. On various Facebook groups related to SMA I hear people describe themselves as “a strong Type 2” or “a weak Type 2”. I have a Facebook friend who lives in Canada and we are both Type 2 but her current physical ability at age 50 is about where I was at 21 or 22.

The disease causes an overall weakening of your muscles. It does not involve any loss of sensation or paralysis. The muscles just gradually get weaker a.k.a. “atrophy”. It is actually a neurological disease however not necessarily a muscular one although it is often lumped into the general category “muscular dystrophy”. There are nerves in your spine called motor neurons. They are responsible for making your muscles move. They have nothing to do with your sense of touch or sensation. The motor neurons quit working and eventually die. That causes the muscles to atrophy.

The disease is in some ways similar to ALS or Amyotrophic Lateral Sclerosis. Although the root causes are very different and the progression of the disease is different, both of them involve the loss of function of motor neurons. ALS is often referred to in this country as Lou Gehrig’s disease because of the famous baseball player who had it. In Europe especially the UK it is referred to as Motor Neuron Disease. Its most famous patient was renowned astrophysicist the late Stephen Hawking. So while there are some similarities, they are completely different diseases.

Okay how does it work? Why did I end up like this?

In every cell of your body you have 23 pairs of chromosomes. Chromosomes are coiled up strands of DNA. Sections of the DNA strands called “genes” are strands of instructions that tell your body how to do different things. DNA is made up of 4 molecules chained together like a twisted ladder. You’ve probably seen drawings or models of it. Each rung of the ladder is made up of two molecules linked together. The 4 molecules that make up DNA are called A and T or C and G. The order of these four letters is a kind of code. The strings of code are divided into sections called exons and introns. The exons are the code and the introns are just sort of filler material.

In your number 5 chromosome at a location called 5q13.1 is a gene called SMN 1. SMN stands for “Survivor Motor Neuron” gene. It produces a protein called the SMN protein. Without a sufficient quantity of this protein, your motor neurons die and then your muscles weaken and presto… You’ve got SMA.

In people with SMA like me, there’s a mistake in the SMN gene. The seventh exon is missing. Think of the chromosome as a strip of movie film where you cut out a section and spliced it back together. When DNA gets copied when your cells duplicate, it tends to get copied in chunks. The ends of the chunks are like pieces of a puzzle that only fit together in certain ways. You have probably worked a jigsaw puzzle where there were pieces that almost fit even though they weren’t the right ones. It just so happens that the ends of the chunk around that particular exon are similar enough that under the right conditions (I guess I should say wrong conditions) they can stick to one another forming a small loop. That leaves a gap in the film strip and even though they aren’t quite right, those pieces end up sticking to each other and the little ring of DNA gets lost.

Once a mistake occurs, it’s passed down generation after generation through carriers of the disease. But it is technically possible that that mutation can spontaneously occur and someone with no history of SMA in their family could get the mutation when that little ring accidentally forms.

Once you got a screwed up SMN1 gene, it’s not going to make the proper protein, and so you’re screwed. Almost…

As Jeff Goldblum famously says in all of the Jurassic Park movies “Life finds a way”. Mother Nature or God or natural selection or whatever you believe in… Has a backup plan. There is another gene that everyone has further down the fifth chromosome called the SMM2 gene. It’s a backup copy. In fact some people have multiple backup copies. But there’s a problem… The backup got corrupted. In the long strings of A, T, G, and C there is a one letter mistake. Think of it as a single bit error in a computer code. Everybody’s SMN 2 genes have this mistake. The end result is that SMN2 only works on average about 20% of the time. So even if your SMN1 gene is totally screwed like mine, the SMN2 occasionally makes up for it. But it’s just not enough.

Now that we’ve established that the cause is a missing chunk out of your SMN1 gene, how does that get passed on?

As mentioned previously everyone has 23 pairs of chromosomes. You have 2 number 1, 2 number 2 etc. You’ve got one of each from each parent. The problem is in my fifth chromosomes. We each have two of them. One came from mom and one from dad. My mom and dad were both “carriers” of SMA. That means that in their fifth chromosomes they had one that was normal and one that was damaged by having that number 7 exon missing. They don’t exhibit the disease because their good copy on their other number 5 chromosome covers it up.

When I was conceived, I had a 50-50 chance of getting either a good copy or a bad copy from each of them. If I got the good one from both mom and dad (25% chance) I would’ve been okay as would my children and children’s children etc. If I had gotten a good one from mom and a bad one from dad or vice versa then I would be a carrier as well. Each of those has a 25% chance for a total of 50% chance of being a carrier. The remaining 25% chance is that I got the bad copy from both. Lucky me! I got the bad copy from both.

My sister Karen obviously does not have the disease so one of three things has happened. Either she got 2 good copies, she got a good one from dad and a bad one from mom, or she got a good one from mom a bad one from dad. That means there is a 66% chance she is a carrier. If her husband is not a carrier as well, her kids are at no risk of actually getting the disease. Her only son Cole is fine.

Because we know that my mom and dad were both carriers, that means that at least one grandparent on each side was a carrier. That means that my Uncle Keith on my dad’s side or my late Aunt Jody on my mom’s side have a 50-50 chance of also being a carrier. If they are not carriers, none of my cousins are at risk nor will their descendants carry it. If Keith or Jody are carriers, my cousins could not exhibit the disease unless Aunt Barbara or Uncle John were also carriers. None of my cousins nor their kids or grandkids so far have exhibited the disease. If my Aunt or Uncle were carriers, my cousins have a 50-50 chance of being a carrier themselves.

But what about me?” Pardon me quoting the old joke “I have no children… That I know of :-)” and at age 65 with no romantic involvement in my life I doubt that I will. But there’s no reason I couldn’t have children. What about them? People who have the disease of course pass it on to their offspring and so technically they are carriers but usually we reserved the word “carrier” for someone who carries the gene but does not exhibit the disease. But anybody with the disease does automatically pass it on. I’ve got two bad copies of the gene so at minimum, all of my kids would be carriers. If my wife was not a carrier then that’s all the risk we would have. If she was a carrier, half of our kids would have SMA and anyone who did not have it would be a carrier. If my wife had SMA, we would both have 2 bad copies and therefore ALL of our children would have two bad copies and have SMA.

They just take a blood sample and send it to a genetic testing lab. They sequence your number five chromosome and look for the missing chunk. If you’ve got a double deletion like me you have the disease. If only one of your two number five chromosomes has a deletion they can tell that you are a carrier. These tests can also be performed prenatally using amniocentesis or by testing in vitro cells prior to implantation. Which brings us to our next topic…

Short version… Become a Nazi.

Either kill or sterilize everyone who is a carrier. They will never pass on their defective qualities and in one generation SMA will be virtually wiped from the planet. We become a super race of genetic perfection and rule the world. There is the possibility of spontaneous mutation by creating that little DNA ring by mistake that I talked about earlier. We can kill those people off as we find them.

Alternate solution only slightly less drastic… You can test for SMA by doing amniocentesis. If it turns out that your unborn child will have SMA, abort it.

Further solution only slightly less drastic… If you do in vitro fertilization (otherwise known as a test tube baby) conception occurs outside the womb. The fertilized egg is allowed to grow until it is a small clump of cells. You then extract a cell and test it for SMA. If it has SMA, you flush the embryo down the toilet and only implant the healthy ones. Sorry… that toilet comment was just speculation for dramatic effect. In reality the embryo is probably incinerated in an oven. We are Nazis after all. Right?

While I don’t know of anyone actually going around sterilizing or killing SMA carriers these days, I’m sad to report that abortions and selective in vitro procedures are being done to avoid having children with SMA.

In short… These people believe that people like Chris Young ought to have never been born.

Pardon me if I take that personally.

I’ve never been opposed to abortion just because the Catholic Church says so. I’ve always felt it was a really bad idea through my own innate conscience and sense of morality. Then I am especially opposed to abortions which implement such selective breeding practices. It turns human life into an animal commodity for breeding purposes rather than the sacred thing that it is.

You could ask hypothetically what would a person be like if they had not caught some disease like polio or AIDS? You can ask what if they never suffered a spinal cord injury or had cerebral palsy due to anoxia during birth. But you can’t say what would someone with SMA be like without it. It’s genetic. It’s part of who we are.

Despite the harshness with which I have described this situation, I am sympathetic to parents who are facing tough decisions when they know that they have the potential to create SMA kids. The situation is especially complicated by the fact that there is no genetic test to determine which type of SMA a particular kid will have. As a Type 2 person who has lived 65 years and had a pretty good life in which I’ve made lots of effort to make the world a better place because I was in it, it’s easy to condemn anyone who doesn’t want people like me to be born. On the other hand Type 1 kids have it much, much harder. As I mentioned before, without serious intervention their life expectancy is 18-24 months. That intervention involves having a trach, ventilator, G-tube for feeding, 24/7 care, and a seriously impaired ability to do much constructive with their lives. Nobody wants to see their kids suffer.

I feel a strange connection to the Type 1 kids. Basically I’m in the same shape at age 65 as they are at age 2-3.

I have no problem whatsoever with parents who choose not to have children if they feel ill prepared to provide adequate care for a child with SMA. All parents should assess their capacity to deal with parenthood and all that it might entail before deciding to have a family. That is the responsible thing to do whether you have genetic risk or not. But I draw the line at selective breeding.

One also has to take into consideration that there now is a treatment for SMA if not a cure. The mortality of Type 1 is not as significant as it once was. More on that in the next section.

I recently encountered a family online who was considering preselection of in vitro embryos to avoid having a kid with SMA. They had already lost a Type 1 infant and could not bear the idea of suffering another such loss. They were opposed to the idea of abortion so I give them some credit for that. I can’t begin to imagine in my wildest dreams what they’ve been through. So it’s tough for me to sit in judgment of them. I really can’t.

On the other hand… I also met a family online who had a kid with SMA Type 1 and were inspired by the experience to adopt other special needs children.

Life finds a way.

Up until recently you couldn’t do jack shit. All you could do is try to mitigate the consequences of the disease.

I wore a back brace from the time I was five years old until my early 20s. It was basically a corset made of cloth and metal stays that we bought from the Spencer Corset Shop. Then in my 20s I switched to a plastic body cast the kind used for treatment of scoliosis. My spine has 2 curves in it 90° each. For various reasons at an early age I quit going to orthopedic doctors because they weren’t doing anything for me. That was a mistake. I should have had spinal fusion when I was a teenager. Most kids with SMA these days do get spinal fusion. They also get metal rods earlier than that that can be adjusted as they grow.

The biggest risk for people with SMA is respiratory issues. I’ve had pneumonia a couple of times. Most people with SMA use a device called a “Cough Assist” that helps them keep their lungs clear. They use it a couple times a day for prevention and every few hours if they have a cold or flu. Until recently I never knew such a device existed and I’ve never used one. I didn’t get my diagnosis until I was nearly 40 and none of my doctors knew what I had or what to do about it. When it comes to SMA specific medical care I’ve basically had none.

I started using oxygen at night to help me breathe better. That came after I developed congestive heart failure in my early 20s. Eventually I added a CPAP machine along with the oxygen. Then read in December 2016 I had to have a trach installed and the CPAP got replaced by a ventilator that I still use with oxygen but only at night. Here is the story of how I ended up with a trach.

Swallowing is extremely difficult. In May 2016 I got to the point where I couldn’t swallow very well anymore and so I had to have a G-tube installed. As I mentioned before, the Type 1 kids end up on ventilators and with G-tubes at a very early age. I’ve encountered many Type 2 people who also got a G-tube much earlier than I did and is not unusual for them to need a trach and ventilator eventually as well. Here is a blog post about when I got my G-tube.

Bathroom issues have always been a problem for me. In 2009 I had a ruptured intestine from diverticulitis and temporarily had a colostomy bag. However after about three months I had the procedure reversed and since then I have pooped “normally”. For many years I would use my Hoyer to lift me onto the toilet but in recent years that hasn’t been very comfortable and I’ve had to use a bedpan.

In September 2019 I had a suprapubic catheter installed in my bladder. If the tube that goes through a hole in my lower abdomen and empties my urine into a leg bag. Although I’m still susceptible to urinary infections overall it’s been a great solution I sort of wish I had done something earlier.

The issue of not being able to directly treat the disease but only its side effects changed dramatically in December 2016 when the FDA approved a new drug called “Spinraza”. It has shown dramatic positive effect on the young severe Type 1 patients. It’s not a cure. It doesn’t always work. In fact in the clinical trials it only works in about 56% of the patients. But considering the severity and mortality of Type 1 patients, it is a real godsend. When it works, the kids stay off the ventilator, there are even signs that some of the effects of the disease are reversed.

The positive effects of the drug were so dramatic during clinical trials that they opened the test from its double-blind format. Typically half of the patients get the drug and the other half get a placebo. But because it’s got such high mortality, once they discovered positive benefits they could not morally withhold the drug from the other kids. For the remainder of the trials everyone got the real deal.

The clinical trials were only for Type 1 kids who were very young, the FDA approval was for all types and all ages. I can get the drug if I wanted. The problem is, I can’t see it having any positive effect on someone my age and my state of deterioration. It’s not just a simple pill. It involves spinal injections in an outpatient hospital procedure every few months for the rest of your life. One time an anesthesiologist looked at my spine to see if I could get an epidural for some surgery I was having. He took one look at me and said “There is no way I’m sticking a needle in that crooked thing”. The long-term side effects of the drug are yet to be determined but respiratory issues are one of the listed side effects.

Because this is a so-called “orphan drug” for which there is a very, very small market, the drug company has to charge exorbitant prices to recoup their development costs. The first year of treatment costs about $750,000 and every year after that $450,000 per year for life. Both government and private insurance have been very reluctant to cover it. If they do it is more likely only for the very young Type 1 patients although some older Type 2 and 3 are getting the drug. It also depends on what country you live in. My friend in Canada cannot get it. Much of the UK cannot get it although Scotland does support it. Australia does. Brazil doesn’t. It’s hit and miss around the world.

Keep in mind that the progression of the disease is that the motor nerves die and that makes the muscles atrophy. This does not regrow the motor neurons. It only prevents them from dying. So the best case scenario for older patients is that they get no worse. If I was in my 20s I would be beating down the door to wherever they had it to get it. But at age 65, with limited upside and potential downside, it just doesn’t make sense for me.

Here is a blog that I wrote in December 2016 the day after the FDA’s approval came. It recounts the story of why it took me so long to get a diagnosis that I did have SMA. It also tells a humorous story about my encounter with the head of the Genetics Department where I used to work as a computer programmer. Although it includes some of the information I have already discussed above, if you’ve not read it before I encourage you to check it out.

Here is the link to another blog I wrote about the cost of Spinraza and those who seek to blame the drug company for its exorbitant price.

I mentioned that everyone has an SMN 2 gene and possibly multiple copies of it but they don’t work very well. Because of that one bit error, the process of copying DNA to RNA and RNA creating the protein just doesn’t work. Spinraza makes it work better. It makes it so that the failure of SMN 2 to properly create the SMN protein is not as bad. There has been a big focus on how many copies of SMN 2 you have because that makes Spinraza potentially more effective.

I wondered what causes the difference between Type 1, Type 2 and Type 3 and speculated it was how many copies of SMN 2 that you have. But apparently there are other factors. There is a variability in how well SMN 2 works from person-to-person. So it’s a combination of a lot of factors. Some insurance companies will only approve Spinraza for people who have multiple copies of SMN 2.

In May 2019 a new treatment was approved by the FDA. It is a gene therapy called Zolgensma. It is only approved for Type 1 patients age 24 months and younger. Here is a link that explains how it works.
https://www.zolgensma.com/how-zolgensma-works
In brief it is given by an IV injection. This is just any ordinary IV and is not a spinal injection like Spinraza. What they have done is taken a working copy of the SMN1 gene and inserted it into something called a vector which is basically an inert virus. The virus carries the new gene throughout your body and deposits it in your motor neurons. At least that’s what the video says. I would think it would deposit it everywhere but what do I know? It doesn’t actually alter your existing DNA. It just throws in an extra free-floating chunk that does what your damaged chromosome 5’s SMN1 gene doesn’t do. Once it has deposited the piece of DNA into the nucleus of your cells, the vector disintegrates and is excreted as waste. The cell then uses that extra piece of DNA to create SMN1 protein.

This is a one-time treatment whereas Spinraza is a new spinal injection every four months. You may have thought that Spinraza was ridiculously expensive. Zolgensma runs at about $2.1 million for a single dose. The last I heard, that makes it the most expensive drug per dose in the world. But if you consider the lifetime cost of Spinraza at about $350,000 per year it makes Zolgensma cheaper. Imagine what it would cost to created drug that you would take only once and never need to take it again. The development costs of most drugs is spread over hundreds of thousands or even millions of patients and spread over millions of doses. But a small population like SMA and a one time treatment it’s really difficult to recover your development costs.

The catch for someone like me is as I said, it’s only available for infants 24 months and younger. So it’s not available for me. There has always been hope that it would eventually be approved for older patients. As I understand it the sticking point is that this drug has a possibility of causing liver damage. If it was to get approved it would probably have to be a spinal injection like Spinraza so that it could get straight to the motor neurons and not necessarily have to pass through the liver and cause possible damage. Apparently infant liver is not as susceptible to this damage as it would be for older patients. I’ve not heard anything recently about them expanding it to older patients. If they ever do offer it to patients my age I might consider it considering it would be just a one time event.

Option 3 Evrysdi a.k.a. Risdiplam

In August 2020 (this month as I’m writing this) the FDA has approved a new drug called Evrysdi which is the new brand name for a drug we have previously been calling Risdiplam. It is an oral treatment that works the same way as Spinraza in that it makes the SMN2 gene work better. It is mixed as a liquid that you can drink or take via a G-tube daily. The idea that you don’t need to have an outpatient procedure to stick a needle in your spine makes it very appealing. In fact I have already decided that I will be looking into taking this treatment assuming that Medicare/Medicaid will approve it. The approval is only a few days old as I’m writing this update so it is still full of uncertainties about things like price and insurance coverage. In all likelihood it will be expensive on the same order as Spinraza.

One of the listed side effects is that it can likely cause birth defects in pregnant women and infertility in men. At age 65 with no wife or girlfriend this is a nonissue for me. But already in the Facebook forums parents of kids with SMA are debating whether or not Evrysdi is appropriate for their kids if it means ruining their chance at having children. There is speculation that you would temporarily go off the drug when trying to conceive but I haven’t read anything official that indicates that the possibility. The websites mentioned that you might want to collect and freeze semen for future use before taking the drug. So I’m sure that will be a big topic for further debate.

Here is the link to an article about Evrysdi and its new approval by the FDA.

Evrysdi (risdiplam) for SMA

There was a recent article linked here https://smanewstoday.com/2018/07/23/motor-neuron-death-sma-linked-abnormal-rna-editing-study/ It explains why the motor neurons die off when they don’t have enough SMN protein. It has to do with the regulation of 2 other proteins called Mdm2 and Mdm4. If they could find a treatment that would regulate these other proteins then you can keep the motor neurons from dying without fixing the SMN problem itself.

There is also a lot of talk about using stem cells to regrow the dead motor neurons. None of the available treatment options can repair the damaged motor neurons. That’s one of the reasons that none of these options will do me a lot of good behind slowing or stopping further deterioration. Regrowing nerve cells from stem cells has been the goal of all sorts of spinal cord injury treatments. To date that has not come even close to working. Christopher Reeve expected to be walking in 10 years after his spinal cord injury and it didn’t happen. He died years ago waiting on it to happen any day and people are still waiting.

The outlook for some like me really isn’t a whole lot brighter given these treatment options. Having lived with the disease for 65 years I’ve probably lost the vast majority of my motor neurons and short of some sort of stem cell regenerative treatment that’s not going to change. The best that these new treatments can do for me and other older patients is to slow down or perhaps stop the progression of the disease. As I mentioned before, if these treatments had been available when I was 20 something or younger I would’ve been jumping on immediately no questions asked.

I have to revisit the issue of selective in vitro implantation and abortion in the light of these new treatment options. The kids who have been treated at a very early age (less than 12 months) are showing amazing results. Some kids who have gotten early treatment are basically exhibiting no effects from the disease and are progressing completely normally. It’s my hope is that parents who are considering selective implantation of in vitro embryos and possible termination will consider that the outlook for their kids is not quite as bleak as it once was.

Those who know me, know how long-winded I am and if you made it this far then I’ve proved that reputation. But there are a million other questions we could answer. What do you want to know about SMA? About my life with SMA? Don’t hold back anything. If we are going to create awareness then let’s create some full awareness. I would rather you not respond to comments on this blog but ask me your questions on Facebook where I’m going to post the link to this article. You can read my page on Facebook even if you are not a Facebook member. Or if you are a member you can follow me without friending me. Or go ahead and friend me. Find me at https://www.facebook.com/cyborg5

I mean it when I say ask me anything. It is EXTREMELY UNLIKELY you can offend me. (Never say never). There is a slim chance I will choose not to answer something personal. But there is a much greater risk that I will answer your question in very much more detail than you ever really wanted. So ask me anything but beware you might get an encyclopedia worth in reply. If it is a long answer I may make another blog out and it. If it’s a quickie I will just answer on Facebook.

Recently a famous YouTuber named Shaun Burcaw also has SMA Type 2 posted a video titled “Things You Should NEVER Say To A Disabled Person”. I agreed with about 95% of what he had to say but I felt compelled to make my own reaction video to address additional issues about the things upon which we agreed and to outline my feelings about the issues where we disagreed. And as I said above, I’ve got pretty thick skin and its almost impossible to offend me. So don’t let that video scare you away from talking to me or asking questions. Here’s a link.

I’m also a member of five or six Facebook groups for families or patients with SMA. They are closed groups that I can get you links to request membership on request.