Advice for Genetic Testing- C9orf72 gene

[concernedwife]

Hello All,
I have so much respect for the members on this forum and certainly do not want to burden anyone. I am a nurse (although never in neurology) but am looking for some insight from people who have lived through some of these experiences...

My husband's family carries the C9orf72 gene. His father is one of 4 children. 2 of his father's sisters are positive for the gene (this has been confirmed). One has since passed away from ALS, the other is currently living with advanced FTD. Both were diagnosed in their 50's (age 52 and 57 at diagnosis). Of note, their father also died from "dementia" although I suspect it was FTD (he was in his 70's). My father-in-law and his other sister are currently both in their early 70's and healthy and both are adamant about not being tested for the gene. I understand, of course, that this is their decision.

My husband is 36 and we have 2 small children. He feels confident he does not have the gene since his dad is healthy and older than his aunts were at diagnosis. I understand this is probably the case, however not necessarily true. We can only be certain with testing. I, personally, would like him to be tested because I have read about some promising trials should he be positive for the gene. I am hopeful that by the time my children (currently 2 and 4 years old) would present with the disease there would likely be a treatment (or hopefully a CURE!!!!). I want to encourage my husband to be tested, but am not sure how to be supportive and understanding. Has anyone been in this situation? Would it be beneficial to know in your opinion? My feeling it that the science looks SO promising and knowledge is power, but I say that as a healthcare provider of course.

Looking for any insight. I very much appreciate your time!

M

 

[Nikki J]

I too believe there is a lot of promise for the future. My neurologist has told me not to worry about the children in my family ( the youngest being late teens). I think there is a lot of hope for your husband should be turn out to be a carrier.

everyone has to decide about genetic testing for themselves though if you were planning a pregnancy I would say differently. I tested when asymptomatic pretty much as soon as we confirmed c9 was our issue. However only one of my at risk cousins ( children of people who were affected) has chosen to know. That is their choice as it is your husband’s.

as a second degree relative of a known c9 carrier he is not likely to be eligible to participate in research. There are studies you can do without knowing but understandably they want to use scarce resources on people most likely to be affected.

I have hope that the equation will change in the next 2-3 years. Biogen currently has a trial for asymptomatic carriers of sod1 for tofersen the sod1 aso. They have completed their phase 3 for sod1 PALS and we are awaiting data. the phase 1-2 looked promising and anecdotally there have been hopeful reports
the equivalent aso for c9 is wrapping up phase 1 and we are anxious to see that data. Praying it is good enough to continue to another phase. I have been told repeatedly that biogen is anxious for an asymptomatic trial for this too. This will depend on good results in PALS and also having strong early biomarkers for c9 onset ( why carrier research is vital)
this is something you should watch because if it happens it will be highly competitive and they will only accept documented carriers. They aren’t going to do initial testing to screen

if either your fil or aunt in law are interested there are study opportunities for them as first degree relatives. They could choose not to know their status. If either turned out to be an asymptomatic carrier at their ages it would be of particular help as one of the things they are looking at is whether there are genetic modifiers ( protective or deleterious)

 

[concernedwife]

Thank you so much, Nikki, for your thoughts.

What is the best way to stay looped in on what research is taking place? I’d appreciate any resources because as you mention there seems to be so much in the pipeline.

My husband does also have cousins (children of his aunts positive for the gene) who have chosen not to be tested. It’s hard for me to accept given my medical background and belief in the science but I, of course, respect their wishes.

 

[Nikki J]

Those cousins could also help in research without knowing if they chose. Being in research studies is the best way to keep in the loop but of course that isn’t open to you

keep an eye on biogen and Wave life science for their aso trials. Drs Michael Benatar, Katharine Nicholson, Tim Miller Matthew Harms and Neil Schneider are studying carriers. Dr Robert Brown UMass, the Angel ALS Fund is working on gene therapy

there is a facebook group for FALS. There is a FALS team at IAMALS