Vijay’s Proximal Origin Story
The first signs of my chronic illness appeared in early 2015, when I noticed limits to my athletic performance. A much sharper decline occurred in 2021, along with a diagnosis of ME/CFS . I’ll recount the full story at a later time, but the proximal origin story of Ansyme begins around the start of 2023, when the first ideas appeared in a flash ⚡ and then a flurry ❄️, or more precisely: two flashes about a month apart in early 2023, and then a flurry of research findings I noticed later that year.
Rewinding slightly, my 2022 was spent mostly bedbound w/ short upright activity bursts for activities of daily living, adding up to ~2,000 Garmin steps/day. My circumstances felt similar to this profile of a leading astronomer in Scotland: bursts of cognitive activity from bed, spread out over time, allowed me to continue fulfilling a reasonable fraction of my professional duties.
That November, I took a few days with a bit more upright activity to choose a condo, picking one with an outdoor patio where I could receive visitors while reclined. For that short period, I successfully traded cognitive activity for upright activity, but there was payback: much reduced cognitive capacity the next week back to work. I remember failing to complete several work tasks which were routine intensity the week prior. In December, I took extended vacation time to gradually pack my belongings, a few crates a day.
Those boxes waited for my move-in date on Wednesday January 25, 2023. On the Sunday prior, I started midodrine, which my primary doctor thought was worth a try given a finding of orthostatic hypotension in his office. I didn’t notice much effect at first, still focused on my usual work routine. I was optimistic but guarded: none of the dozens of supplements nor prescriptions I’d tried before had a clear and durable positive effect. I didn’t have extended vacation time for my move-in, so I planned to hire a “tasker” to help unpack and set up.
But no tasker was needed! On move-in day, I remained upright most of the day, accompanying the moving truck, moving a couple of rental car loads , and supporting the cleaning team at my old place. When the weekend came, I completed most unpacking solo, with two straight days of over 10,000 steps. And there was no notable setback to recumbent cognitive work the following week.
My Jan 2023 move was an accidental experiment revealing a major capacity gain for a comparable task after midodrine onset: more Garmin steps, faster task completion, less payback for the move & unpacking. Some of the initial large gain has held up with time.
That was the first flash ⚡: midodrine, a lower nervous system drug not considered to cross the blood-brain barrier (BBB), dramatically increased my capacity in short order. And the gains proved more sustained than anything I had tried before. I briefly pondered if I might be cured, and was fully confident I was up to a short (human-powered) 1 mile BlueBike ride on Feb 15, 2023 to reach a UPS store before it closed. While I barely completed the errand, I was humbled and had to use the Commonwealth Avenue carriage lanes, after discovering I did not have the acceleration needed to stay with traffic. My step counts declined in the following weeks. This short, slow 20 minute ride had triggered post-exertional malaise (PEM) with baseline decline.
My second flash ⚡ was another locomotor defect noticed on a later (unrecorded) date in February: though my walking was normal and sometimes brisk, I was unable to initiate a jogging motion. From a walking standpoint, it was as if the mostly bedbound year simply hadn’t happened. One day, the pedestrian crosswalk light flashed as I started to cross the street, and I instinctively initiated a jog, as I’d always done. To my great surprise, my body simply could not start the motion despite my clear expectation and top-down motor command. In the months ahead, this limitation lessened, without any explicit rehabilitation. For a few months in the fall, I took a monthly video to capture the last stages of this strange locomotor defect. My short jogs/runs, each undertaken with full intention, became gradually less “hindered”:
This second flash immediately triggered greater interest in the lower nervous system. While I’ve long worked with neuroscientists, my discussions have mostly centered on their experimental technologies. Now I was reaching out to my network to talk science. Discussions on the neuroscience of locomotion revealed that spinal cord central pattern generators for locomotion are posited in the human nervous system but are still considered a mystery. I was also informed about the 2022 BRAIN Prize awarded for the role of the brainstem of movement control, including gait.
In late 2023, a flurry❄️of brainstem findings began appearing in the neuroscience literature from a broader set of authors: a UCSD-led team explained vasovagal syncope and a Northwestern team found a likely explanation for bradykinesia in Parkinson’s Disease. These studies, and many more that began appearing regularly in 2024, convinced me that the lower nervous system is a key component of my chronic illness and that advanced neuroscience now has the tools to generate answers and potential interventions for many health conditions. Most of these studies used technologies arising from the decade-old US BRAIN Initiative, which ran into funding challenges in mid-2024. I tried my best to encourage BRAIN scientists to highlight their newfound capabilities to address chronic illness, but BRAIN self-advocacy largely remained limited to its impacts on spinal cord injury and mental health. Perhaps this may change, but it began to seem the ball landed in my court. Hence Ansyme.
Since those eventful first two months of 2023, my health metrics have remained much improved: I’ve averaged >4000 steps/day since and my cognitive work is now “semi-recumbent” in a recliner. Steps don’t tell the whole story however. I lack exercise tolerance; in September 2024, I was inspired by Katie Ledecky’s story to try recumbent exercise, but my second-day short 6 minute medium-intensity workouts provoked a multi-month baseline decline, reversed in December upon stepping up my midodrine dosage. Additionally, my cognitive uptime and physical upright time are two key health metrics. My cognitive uptime is limited by, for lack of a better term, daily “incapacity episodes” which are unpredictable dropouts in cognitive (and physical) task capacity. They may be akin to “nonsleep deep rest”, but they’re involuntary, akin to narcolepsy, and usually fully recumbent. My physical upright time is limited by delayed and also unpredictable onset of heart rate ramps, mild hypotension (even with midodrine), post-exertional slumps lasting days, and baseline drops lasting months.
These limitations are considerable and frustrating, and yet I’m also fortunate to have lifted out of severe ME/CFS through intervention(s) targeting the lower nervous system.