Pat Tagert here. As a handful of you may know, my son died last summer, just 18 days after Steven Keating. He was diagnosed with sporadic ALS at the age of 33, and lived another seven years, the last 18 months on a ventilator. He was the most prolific user of TOBII eye gaze technology in Canada at the time of his passing, controlling his electronic environment with few limitations with the help of the eye gaze technology.
As some may know, amyotrophic lateral sclerosis (aka motor neuron disease, aka Lou Gehrig’s Disease) is typically a disease of late onset. The most prevalent age at onset is in the 7th decade. A small fraction of ALS is of familial Mendelian origin, estimates of 5%-12% of all ALS, probably nearer the lower %. Researchers have learned most of what they know about ALS by sequencing and analysis of those with familial ALS. Familial ALS, depending on the variants involved, can occur at almost any age, from very early childhood to late adult onset. Sporadic ALS mostly occurs between the ages of 50-75, with the incidence dropping off after that. I had always imagined that ALS was a very rare disease, the proverbial “one in a million”, but certainly not so, per the latest statistics. Researchers last year at Trinity University of Dublin, targeting only persons of native Irish ancestry, who published after an approximately 10 year study in Ireland, discovered that native Irish have an approximately 1 in 340 probability of ALS (I averaged between male and female statistics). Satistics are similar for Britain, and Finland is another hotspot.
More than 5 years ago (after it became apparent that no institution/researchers were interested) I tried to do an “ad hoc” trio research for my son, using my PGP whole genome, and whole exomes I bought for my son and his mom. My goal was simply to discover any causal variants. I failed miserably of course, and worse, it became a distraction while my son’s disease progressed. Near the end I discovered a potential causal variant (but with low confidence), and by then I had come to realize how completely inadequate all my efforts had been.
The most obvious first thought for most observers might be “okay, but why so much emphasis on discovery of causal variants?”, and of course the answer is that there is zero probability of a cure without knowing the cause. It’s the first step.
So, there are people every day somewhere discovering that they are going to die from this disease, but most of them have already lived a full life. My son was in his prime when he received the diagnosis, with a young son of his own. I had no idea where to turn for information, so I learned as best I could and blundered along, and mostly what I have learned is just how far I was from access to the technologies that might have made a difference.
So, that’s my project. What kind of technologies are available, at what cost, and how can people suffering from sporadic ALS (and especially young people) gain access to these technologies, so that every tiny facet of their genomes is thoroughly explored, no stone left unturned? Of course, the obvious problem is how to pay for it, but that can’t be determined without first knowing the cost.
The next time a young family man starts feeling fasciculations and starts to lose his strength, where can he turn to find out what’s causing his disease, if all the “usual” options are out of reach?? I want to know what it costs to get a de novo assembly whole genome sequence, with every remote niche of the genome explored in it’s entirety, no loose ends,and all related technologies, including methylome testing for epigenetic modifications. That’s the only hope for discovering what’s causing this dreadful disease, and in fact, there are obviously many causes for ALS, as there are for all complex neurodegenerative diseases, and it may be that most patients need a 100% genome sequence to discover the cause, while some fraction can discover causal variants with less expensive and more widely available technologies. How then should testing progress in an orderly logical fashion?? Is that ultimately an unreachable goal? I just want to put a $ figure on it, and find out what’s available.