I’ll Tell You Like You’re a Kid: What is C9orf72? What is ALS? What is FTD?
You may ask, “So what’s all this talk about C9orf72?” and I have an answer. In layperson’s terms, too. Let’s start with the name.
This gene occurs on the chromosome 9, “orf” refers to open frame reading, which is where and how science nerds find it, in the 72nd frame of the genetic sequence. Basically, if that gene is normal, the hexanucleotide looks like GGGCC. Most people have this code that repeats between 2 and 24 times. Someone with a mutated C9 gene has a code that repeats hundreds or thousands of times. This is called a dipeptide repeat expansion (mutation).
The C9orf72 mutated gene can cause problems like Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD). So, exactly what is ALS?
ALS is a neurodegenerative disease. It affects 1 in every 300 people worldwide. It causes patients to lose the ability to walk, use their hands, speak, eat, and breathe. And there are lots of ways that ALS can first present itself; everyone’s ALS is different. Some patients lose strength in their mouth and tongue. This is bulbar ALS. Others start with weakness in their limbs. This is limb-onset ALS. Some people have fast-progressing ALS, and some progress very slowly. The typical life expectancy for a person with ALS is 2 to 5 years. It is fatal, and there is no cure.
Here's the important thing for me and my family: “genetic” or “familial” ALS only accounts for 10 to 15% of all ALS. That makes it a rare form of a rare disease. Here’s another crazy fact: some people with the C9 mutation never get ALS. Some get FTD.
“So, what’s FTD?” you may ask. While I’ve never had personal experience with it (my family members have only died of C9 ALS so far), many of my friends have family members who have. Frontotemporal Dementia is a kind of neurodegenerative disease that affects behavior. It can make someone lose the ability to retain language skills, forget things, act in an erratic way, develop strange behaviors, like incessant spending or gambling. It affects the frontal lobe of the brain. And like ALS, it is fatal. There is no cure.
Here's another crazy fact about C9 disease: a patient can get ALS, FTD, neither, or both. For patients with both, they and their caregivers really have a heavy burden. Imagine what it would be like to care for someone who can’t move but also doesn’t understand anything. Sometimes I think about what that would look like for my loved ones, and it gives me chills.
Going back to the basics, here’s the way I see it. For 85 to 90% of ALS patients, sporadic ALS is the disease. For carriers of the C9 mutation, C9orf72 is the disease, and ALS or FTD are symptoms of the disease. And that’s not all.
There have been more than 40 genes implicated in causing ALS. Those of us with C9 make up about 50% of genetic carriers of ALS. There are also several genes implicated in causing FTD. End the Legacy, the organization for people impacted by genes that cause ALS and FTD (www.endthelegacy.org) estimates that there are over 100 thousand people in the US with these genes, and the majority of them don’t even know it.
If this information makes your head spin, you’re not alone. Scientists have known about genetic forms of ALS for more than 30 years, and they’ve only begun to invent treatments for familial ALS. Last year, Toferson/Qalsody began to show promise in slowing the progression of the SOD1 mutation that causes ALS. It’s very exciting for people with that particular genetic mutation, and it bodes well for people with other genetic mutations, but SOD1 is a different kind of mutation; it’s a misfolded protein, which is easier to cure than C9.
“Why haven’t scientists found a cure since they can pinpoint the C9 mutation as a cause of genetic ALS?” you may ask. Honestly, I don’t know. Perhaps the answer is CRISPR gene editing or an mRNA vaccine? I know that science is the answer, so I participate in lots of longitudinal research for C9. I also donate to organizations that specialize in ALS/FTD research.
“What can I do to help?” you may ask. Please read my book, Last Nerve: A Memoir of Illness and the Endurance of Family. It will tell you all about ALS activism. The last page of the book also lists some of my favorite ways to become involved in this battle. Here’s part of my list:
Donate to ALS TDI (ALS Therapy Development Institute). It’s a nonprofit lab that only works on curing ALS, www.als.net.
Participate as a healthy volunteer in Everything ALS’s Speech Study. Use your voice to find digital biomarkers of disease progression, www.everythingals.org.
Attend a webinar about genetic ALS/FTD at End the Legacy. If you’re my friend, you’re affected by my C9 mutation, so check it out at www.endthelegacy.org.
Any other questions? Please reach out to me on the “Contact” section of my website, and we’ll talk!