Yesterday on Good Morning America, NFL Hall of Famer Chris Johnson announced that he had ALS. Johnson, nicknamed CJ2K for his 2006 rushing yards in 2009, was one of the most electrifying players I’ve ever seen. He was impossibly fast. Every one of his carries was must-watch football, as you’d never know when he’d break a run for a touchdown. Johnson still holds the record for the most yards from scrimmage in a season, with his total of 2509 a comfortable 80 yards in front of second place.
Johnson retired in 2018, and, like most football players, disappeared from the national spotlight. So it was beyond heartbreaking to see him yesterday, at 40 years old, speaking to Michael Strahan with an eye-tracking device. ALS attacks the body’s nerve cells, progressively inhibiting a person’s ability to move their limbs, speak, and breathe. Though highly variable, the progression can be shockingly rapid. Johnson told GMA that he had been diagnosed less than a year ago. He wanted to share his story to bring more attention to ALS and the search for radical new treatments.
In 2023, Gideon Lewis-Kraus wrote a moving investigation into this search for The New Yorker. People with ALS and their families are, for quite obvious reasons, passionately dedicated to finding any reasonable treatments for the disease. The hope is to find therapies that at least slow disease progression and improve the patient’s quality of life. The challenge is this tends to require drugs, and ALS lies outside the sweet spot of modern drug discovery.
ALS is a rare but devastating condition, with around 5,000 new cases diagnosed in the United States every year. There is no clear established cause for ALS. Though it typically manifests in people’s late fifties or early sixties, Johnson’s case exemplifies how unpredictable its onset can be. Sometimes ALS progression takes years; sometimes it rapidly advances in months. There are no clear genetic signals for ALS, and family history isn’t predictive. There is a biomarker present in the nerve cells of almost all ALS patients, but current technology only lets us detect this biomarker after death.
Without access to a marker, measuring progression or reversal is a subjective challenge. Current ALS surrogates numerically assess bodily functions like speech, swallowing, breathing, and motor skills, and combine these different tests into a single number. For example, the ALSFRS-R score is the sum of 12 different assessments, each scored on a scale from 0 to 4, where 0 indicates total loss of function, and 4 indicates no loss of function.
All of this adds up to make drug testing a major challenge. It’s hard to define reasonable endpoints, and most trials aim to find a statistically significant difference between treatment and control in ordinal assessments made by clinicians. Though patients and their families urgently seek new possible therapies, there are not enough ALS patients to meet the harsh statistical standards of clinical trials. Moreover, drugs require trials, and the ethics of potentially denying the control group something beneficial are complex and fraught.1
Lewis-Kraus draws connections to the disease that set the standard for patient advocacy against institutionalized medicine: AIDS. AIDS activists in the 1980s were not only vocal in spreading awareness of the disease and its various treatments, but they actively engaged in scientific research and drug policy. It’s a remarkable example of a citizen group not only challenging, but shaping scientific expertise. To this day, AIDS activists remain go-to consultants for helping people and families affected by rare diseases to organize and advocate for the afflicted.
In hindsight, HIV treatment is similar to the treatment of other progressive diseases like ALS. None of the treatments cured an HIV infection, but they allowed patients to manage their infection. Today, HIV can be treated pharmaceutically with an excellent long-term prognosis. Though initially a terrifying death sentence, people with HIV infections can live a normal life with access to the proper medication.
The differences between AIDS and ALS highlight what makes a progressive, terminal condition treatable. AIDS was caused by an infection with the virus HIV. The first effective HIV treatment, AZT, targeted the virus by fooling it to bind to a byproduct of the drug rather than the person’s DNA manufacturing system. This eliminated HIV’s ability to replicate. Moreover, AIDS had an easily measurable surrogate marker to monitor progress. HIV killed a particular type of white blood cell, and counting these cells was a reasonable way to test if the drug was having an effect.
Sadly, while researchers are hopeful that we’re making rapid progress, we’re still missing many crucial causal pieces to the ALS story that might illuminate an appropriate target for the pharmaceutical industry. Johnson hopes that raising awareness of ALS might help us find the missing link in understanding and treating the disease. He wants to keep fighting. My heart goes out to CJ2K, his family, and everyone else suffering from this terrible condition. And I hope his inspiration will help us find the missing gap for a breakthrough treatment.
Gideon also discusses another problem I have to flag: drug companies targeting rare conditions must set exorbitant prices to generate a profit. Let’s pin this dark consequence of capitalism for later.
While the number of incident ALS cases is small, it's more than enough for a targeted clinical trial if you had good biomarkers or a clear causal hypothesis. We've gotten quite good at these rare disease studies and drug development there. The problem is rather that for a disease modifying therapeutic with an effect that is only measurable statistically, like your old cardiovascular examples, you don't have enough N....