Multiple Sclerosis. Everything you need to know

Unfortunately, the exact reverse is also true: "extinguished" demyelination lesions do not mean multiple sclerosis has entered remission. Even after pulse therapy, when a patient experiences a surge of energy and lesions stop accumulating contrast, the disease keeps dismantling brain tissue. The lymphocytes that dug into the brain linings view myelin as their ultimate target, and they see it everywhere. Since the enemy is all around them, they fight: they don't just riot themselves; they coordinate the local immune response, and macrophages systematically devour the myelin sheath layer by layer. Lymphocytes have zero reason to leave the brain—they have already found exactly what fits their receptor.

This is where the most dangerous misconception regarding MS hides. When an MRI fails to show active lesions and symptoms back off thanks to the brain's neuroplasticity, patients sincerely believe that "the disease is in remission" and "the drug is holding". The majority are convinced that the destruction of brain tissue only occurs during active relapses—assuming that immunity attacks the nerves in bursts, cutting off signals. Yet, very few stop to think about the actual biology of this process. A "relapse" is viewed as an explosion of the disease, and "remission" as a total ceasefire. If a patient is using a DMT during a window of calm, they credit the medicine for the remission, and when a relapse strikes, they declare that "the DMT stopped holding". The baseline condition that "the drug was holding" and that it deserves the credit for the calm is a dogma that is never up for debate.

Well, the truth is far less comforting: if after a few years of taking a drug you experience a relapse, it actually means the drug failed to protect you from it, even if it was working. The relapse occurred because immune cells had been quietly devouring your myelin over a long stretch of time. The nervous tissue kept degrading, but as long as the brain managed to compensate for the damage through neuroplasticity, you felt zero symptoms. At some point, the "neurological reserve" topped out, and the symptoms broke through—sometimes smoothly and invisibly, sometimes in a sharp flash. The main thing you need to grasp is that the destruction of nervous tissue doesn't just happen during relapses; it happens continuously. A relapse is the breakthrough of symptoms, not the awakening of the disease. On the contrary, sclerosis was working overtime the entire time leading up to that relapse.

The core of the issue is that everyone has been trained to measure MS activity entirely by the number of burning lesions. If there are no contrast spots, the disease is logged as being in remission—even if the patient's symptoms continue to intensify. In reality, a demyelination lesion doesn't accumulate contrast forever. Over time, the autoimmune process dug deep into the brain tissue and stopped disrupting the blood-brain barrier. The healing of the vascular wall doesn't mean demyelination has ground to a halt. For example, shortly after pulse therapy, lesions stop burning—yet this doesn't mean the autoimmune process has been snuffed out. The wall is patched up, but the troublemakers who managed to slip through the gate keep rioting, exactly like the anime Attack on Titan. The assumption that the disease enters remission simply because lesions stop accumulating contrast is the most dangerous trap in the entire MS treatment grid.

On the EDSS Scale and the Room for Statistical Miracles

The first scale engineered to measure the status of multiple sclerosis patients was rolled out back in 1955—back then, it was tagged as the DSS, Disability Status Scale. Its creator, John Kurtzke, was an American neurologist working at a US Veterans Affairs hospital. By an ironic twist of fate, we owe the creation of the primary tool for measuring MS progression to a medical error born out of a total accident. Multiple sclerosis is surrounded by misconceptions on all sides, and measuring the degree of disability is no exception.

In the early 1950s, Kurtzke and his colleague Louis Berlin were testing the efficacy of an anti-tuberculosis drug called isoniazid for treating MS. Isoniazid is a highly specialized antibiotic: its sole mission is hunting down the mycobacteria responsible for tuberculosis. How did such a wild idea even enter anyone's mind? It all came down to pure chance: a World War II veteran with multiple sclerosis was admitted to the hospital for tuberculosis, and after being put on isoniazid, his slurred speech suddenly cleared up and his tremors backed off. In Kurtzke’s defense, autoimmune diseases hadn't been mapped out yet; the medical world was hunting for a hidden virus or bacteria driving MS.

Spotting the anomaly, Kurtzke and Berlin ran a pilot test. The results looked promising, and the VA decided to launch a massive trial across 11 hospitals nationwide. To ensure that dozens of doctors in different wards measured shifts in patient conditions by a unified metric, Kurtzke engineered the 11-point DSS scale. Isoniazid flunked the audit: its temporary positive effect on MS turned out to be the byproduct of the natural fluctuation of the disease. The DSS, however, didn't just survive; it flourished. In 1983, Kurtzke updated the metric with 0.5-point increments, transforming the tool into the Extended Disability Status Scale (EDSS). This expansion turned the scale into an ideal instrument for statistical illusions: the EDSS score became a key clinical endpoint in every single DMT trial.

Here is a curious detail: during the trials for the very first interferon, the EDSS score wasn't even the primary endpoint; they only tracked the number of relapses. When the investigators finally pulled up the data charts for the EDSS scale, they got hit with a freezing shower: the disability progression curves for the placebo group and the Betaseron group practically merged. Mathematically, there was zero significant difference in how their EDSS scores shifted. Despite this, the interferon beta-1b rammed through regulatory approval anyway. However, subsequent DMTs were forced to use disability progression as an endpoint, and the flexibility of interpreting EDSS scores turned out to be incredibly convenient.

The structural vulnerability of the EDSS is that the calculator has been stripped down to a single, flattened final score. Instead of evaluating the patient's status across several distinct functional tracks (cerebellar, visual, bowel/bladder, cognitive, and so on), everything was boiled down to a flat text description of the output. Up to 1.5 points maps to minimal impairment; 2.0 to 3.5 logs moderate issues; and starting right at 4.0, everything hinges strictly on walking distance. After 6.0, the patient requires an assistive device to move; after 7.0, they are restricted to a wheelchair; and past 8.0, they are bedridden and lose significant use of their hands. Look closely at this imbalance: from 0 to 3.5, the patient is more or less functional, but the transition from 4.0 to 7.5 is a slippery slide from minor limitations to total helplessness. The non-linear structure of the EDSS is a prime variable for cooking efficacy numbers: hand-picking the right patients for a trial allows researchers to heavily manipulate the final data.

Some medical registries don't even bother separating scores below 3.5—these impairments are dumped into a single basket and labeled as "mild or moderate". This framework grants investigators massive creative freedom when logging disability shifts, which can artificially inflate the proven efficacy of drugs during trials with compromised blinding. If researchers can guess who is getting the drug and who is stuck on a placebo, the fuzzy line between "mild" and "moderate" impairments can manufacture a wall of statistical noise spanning up to two full points. However, past the 4.0 mark, things aren't any cleaner: the scale shifts its focus exclusively to walking distance, completely blinding itself to other issues. If at a 4.0 mark a patient can trudge 500 meters without resting, the scale doesn't give a damn about how well their hands, eyes, cognition, or bladder are functioning.

When a score is anchored entirely to walking, any decline that doesn't involve the legs can be legally ignored. Vision dropped? "Doesn't move the EDSS". Memory loss, speech glitches, or executive decline? "EDSS remains stable". A tremor takes over the hand, making it impossible to hold a fork? "The scale failed to register a shift". Crushing fatigue, an inability to get out of bed, anxiety, apathy, or depression? "Disability metric is completely stable". This obsessive fixation on walking is the primary flaw of the EDSS. When a pharmaceutical giant boasts that "patients maintained a stable score throughout the therapy," in reality, it frequently means nothing more than the fact that they could still walk. What is happening to the brain tissue remains a mystery; fine motor skills are ignored; bowel/bladder issues and cognitive decline are written off. A patient can lose the ability to tie their shoes due to tremors, but as long as their legs clock the mandatory distance, clinical reports will cheerfully log "moderate" impairment.

Yet, the EDSS manufactures a convincing illusion of rigorous science for patients. EDSS 1.5? Great, nothing to worry about, the impairment is mild—it doesn't matter that the patient can no longer read books and has spent the last year working at half capacity. EDSS 2.5? Zero disability progression, it doesn't matter that the patient breaks down crying every evening because they can no longer track their own thoughts. EDSS 3.5? Still no reason to panic, the impairment is moderate—it doesn't matter that the patient has to run to the bathroom every thirty minutes. A hard number for the degree of disability exists—and on that number, you can build a clean chart, a scientific publication, and an aggressive marketing strategy without asking a single uncomfortable question about the patient's actual status. The main thing is to build an illusion of control and keep the patient from realizing that the number doesn't map reality.

In the end, a scale that was engineered to measure neurological deficits turned into a convenient facade used to mask degradation. The EDSS is completely defenseless against statistical juggling. If you need to prove a drug works, you screen for mild patients, deploy the baseline therapy, and watch their legs. If the data fails, you can always claim that "the EDSS missed the improvement because the scale lacks sensitivity". It’s a universal tool—perfect for pushing drugs and equally perfect for dodging uncomfortable data. Patients are hemorrhaging physical power and bodily functions, but on the EDSS chart, "no disability progression is observed".

Are there alternatives to the EDSS? Yes, plenty of them: MSFC (Multiple Sclerosis Functional Composite), PROMs (Patient-Reported Outcome Measures), Floodlight, and others. Among the old guard, almost simultaneously with the expansion of Kurtzke's scale, the Scripps Research Institute engineered its own tracking matrix—the Scripps Neurologic Rating Scale (SNRS). The SNRS measures far more than the ability to walk: it audits muscle strength, coordination, balance, gait, sensory mapping, speech, vision, reflexes, cerebellar functions, eye movement tracking, general neurological integration, and bowel/bladder functions. This instrument is also far from flawless, but in terms of sensitivity and completeness, it sits incomparably closer to the actual clinical profile. In plain terms, the phrase "no disability progression by the SNRS scale" would carry far more weight than an identical claim regarding the EDSS.

Yet, for clinical trials and pharmaceutical reporting, the industry chose the EDSS. Why? Because Kurtzke's scale carried the institutional weight of being used in the US military, and because the extreme sensitivity of the SNRS terrified drug manufacturers. Why deploy an instrument that logs every minor glitch when the EDSS allows you to turn a blind eye to them? As a result, the EDSS became the gold standard of the industry, even though the SNRS could have delivered a far more honest picture. The EDSS is streamlined for rapid auditing—thanks to its instant score generation—but it completely ignores an array of symptoms that dictate a patient's quality of life. Take me, for example: during my worst stretches, I couldn't close my eyes while washing my hair in the shower—I would instantly lose balance and crash to the floor. Yet, this total failure of equilibrium didn't shift my EDSS score by a single fraction of a point.

Chapter 3. The Interferon War

«He rainmade you. A guy says if you pay him he can make it rain. You pay him. If and when it rains, he takes the credit. If and when it doesn’t, he finds reasons for you to pay him more».

The Wire, 2002-2008

The Birth of DMTs: The Wheelchair Assault and Big Pharma’s Lottery

To truly understand how the era of interferons kicked off, you have to flash back to the early 1990s. Picture a world in the middle of a massive tech boom. Humanity is advancing in leaps and bounds. Your neighbor just bought a car equipped with parking sensors, a navigation system, and an automatic transmission. Televisions are in every home, broadcasting news about biotechnology, genetic engineering, and stem cells. Bill Gates has already built Microsoft and is predicting an explosion of something called the Internet—whatever that is. More and more people are carrying mobile phones, and the devices are getting smaller and sleeker by the day. Terminator 2: Judgment Day just hit theaters with mind-blowing special effects. Everything is evolving, shifting, and upgrading at a dizzying pace. But then there’s you. You have multiple sclerosis, and the medical world has absolutely nothing to offer you.

Back in 1980, the WHO announced that mass vaccination had completely wiped smallpox off the face of the Earth. Stomach ulcers can now be cured in a couple of weeks with a simple course of antibiotics, because it turns out a bacterium called Helicobacter pylori was to blame all along. Organ transplantation has stopped being a wild experiment and turned into standard medicine, thanks to a drug called cyclosporine. Genetic engineering has allowed us to use E. coli bacteria to mass-produce human insulin, saving diabetic patients. Vaccines shield children from measles and polio, and even HIV was brought under relative control a few years ago. But you have multiple sclerosis. Your brain is steadily losing ground, and nobody can do a damn thing about it. It feels entirely unfair.

By the early 1990s, interferons were the talk of the town. Time magazine featured interferon on its cover, hailing it as the ultimate "cancer killer." Scientists were looking to use it to cure Hepatitis B and C, and newspapers ran headlines claiming cirrhosis of the liver would soon be a thing of the past. Medical journals published papers suggesting interferon would become the master key to oncology, purging metastases from the body. Doctors injected it directly into warts, promising that a powerful local hit would force the papillomavirus to retreat without surgery. They tried using it to treat colds, chronic runny noses, lupus, rheumatoid arthritis, acute respiratory viral infections, and even atypical pneumonia. But none of this applied to you. You have multiple sclerosis, and medicine has nothing for you.

When the clinical trials for Betaseron wrapped up in 1992, MS patients were desperate for a miracle. On one side of the scales was Chiron, a small biotech firm from California; on the other was the FDA, the rigid federal regulator. Chiron’s scientists had managed to replicate interferon beta-1b using genetic engineering, but they lacked the capital to fund large-scale clinical trials, so they partnered with the pharmaceutical giant Schering AG. When the data came out, it showed a 30% reduction in the annual relapse rate, and Chiron began celebrating a victory over MS. But the boring bureaucrats at the FDA were deeply skeptical. They flagged the side effects and toxicity levels as monstrous, the surrogate endpoints as highly ambiguous, and the link between relapse reduction and actual disability progression as completely unproven. The FDA's verdict was a hard no: "Denied for accelerated approval; return to multi-year clinical trials."

What followed outside the FDA offices in Maryland looked like a civil war. MS patients joined forces with radical gay rights activists from ACT UP. In a series of DIE IN protests, hundreds of people with crutches and wheelchairs blocked the entrance to the FDA building, acting as living symbols of a bureaucracy that was killing them by withholding drugs. They chained themselves to the doors, railings, and parking gates. The police were at a total loss: arresting and dragging disabled people into paddy wagons under the glare of rolling TV cameras was a public relations nightmare. Protesters breached the perimeter, occupying waiting rooms and staging sit-ins in the hallways. Some brought literal coffins painted with the names of people who had died or become severely disabled while waiting for approval. This dramatic footage ran on every major news channel every single night. Terrified by what they saw on TV, senators and congressmen flooded the head of the FDA with calls demanding to "fix this issue immediately."

The ugliest part of this story? The protests outside the FDA were quietly bankrolled by the very companies manufacturing the interferons—Berlex and Chiron. Money was funneled to MS advocacy foundations under the guise of "educational grants" or "patient aid." These foundations, in turn, coordinated the logistics, managed patient databases, and paid for busing disabled people to the rallies in Maryland. Corporate lawyers leaked internal FDA data to the activists—flagging exactly which documents were stalled, which bureaucrats were pushing back, and which offices needed to be targeted next. Worst of all, the patients genuinely viewed the pharmaceutical companies as their allies. Amid the emotional crossfire, the world became black and white: the FDA bureaucrats were the villains standing between sick people and a life-saving miracle.

Betaseron rammed through US approval in the summer of 1993. The official press releases from the FDA and statements by its head, David Kessler, were a masterclass in political gymnastics. Publicly, the officials fiercely denied that they were bowing to the pressure of the streets; privately, they admitted that ignoring the riots was completely impossible. Publicly, they maintained that the protests hadn't lowered their safety standards; privately, they complained that the pressure was unprecedented and entirely paralyzing. Publicly, they claimed they had listened to the voice of the terminally ill; privately, they hinted the orders had come from the White House. This decision warped the FDA forever, transforming it from a closed academic registry into an agency that is forced to bow to public opinion.

By the way, the word "lottery" in this context isn't a metaphor—it was a literal draw. At the moment of Betaseron sudden registration, the US harbored about 250,000 MS patients, with roughly a third matching the criteria for the relapsing-remitting track. At launch, Berlex (the subsidiary of Schering AG handling distribution) could only manufacture enough medicine for 15,000 patients. Distributing it on a first-come, first-served basis would cause absolute riots at pharmacies. Selling it only to the ultra-wealthy would invite public destruction by enraged activists. So, Berlex hired an independent firm and launched the first-ever pharmaceutical lottery.

There were 67,000 applicants for just 15,000 available slots. More than 50,000 people walked away not with medicine, but with a waitlist number. Holding a number like 48,512 meant you wouldn't see the drug for another two or three years. This lottery single-handedly dictated the financial trajectory of the DMT market for decades to come: when you have a product with a 50,000-person waiting list, you can charge whatever the hell you want—insurance companies won't dare object. The lottery was executed right inside neurologists' offices, leaving furious doctors accusing Berlex of "playing God" and outsourcing moral responsibility to a piece of soulless software.

The end of 1993 marked the absolute peak of global hope for interferons. The scientists at the FDA could only watch in disbelief. They knew they were rubber-stamping a drug that had zero impact on the actual rate of disability progression, but they were powerless against public hysteria. Marketing had triumphed over biological reality. Under the thunderous applause of hundreds of thousands of deceived people, interferons hit the pharmacy shelves.

Interferons Beta-1b

Interferons are a family of signaling proteins naturally released by the immune system whenever a virus breaches the body. They were discovered entirely by accident in 1957 by Alick Isaacs and Jean Lindenmann at London’s National Institute for Medical Research. They stumbled upon a fascinating biological anomaly: the presence of one active viral infection blocked a second independent virus from multiplying, both in chicken embryos and lab mice. They termed this "interference"—essentially, a biological obstruction.

The very first drug approved to treat multiple sclerosis was interferon beta-1b. Marketed under the brand name Betaseron, it rammed through US registration in the summer of 1993 following the riots outside the FDA. The annual price tag was set at $9,882—an astronomical, shocking figure that broke the financial baseline of American medicine forever. The drug cost dozens of times more than any standard medication of the era, and the manufacturing deficit—which forced the therapy to be rationed via a randomized computer draw—only fed the hysteria. For comparison, the average annual salary of an American in 1993 sat at $26,362. Insurance companies were forced to engineer a brand-new coverage category called "Specialty Drugs"—prior to 1993, they had never faced a reality where a routine retail medication cost as much as a used car. Betaseron became the most expensive self-injectable drug you could take at home.

This is exactly how the era of DMTs kicked off—built on magical interferons, genetic breakthroughs, wheelchair riots, a corporate lottery, and mind-boggling prices. Betaseron's registration locked down the rules of the market for decades: from that moment on, FDA officials became terrified of MS patients. Prices continued their upward spiral: today, the annual cost of interferon therapy bounces between $80,000 and $140,000—while the median US salary sits around $62,500. The price inflation of interferons has outpaced standard economic inflation several times over, even though any manufacturing deficits vanished decades ago.

In Europe, interferon beta-1b arrived two years later under the name Betaferon. The lag occurred because on November 1, 1993, the European Union was born, and its unified drug regulator, the EMA, didn’t fire up its engines until January 1995. The application for interferon beta-1b became the first-ever high-tech drug submission managed through the new "centralized procedure." It was a high-stakes exam for the brand-new regulator: the agency desperately wanted to prove it could operate faster and more efficiently than the American FDA. Approval went through in record time—by November 1995, just 10 months after the agency opened its doors, the European Commission granted Betaferon its license. European patients, who numbered around 350,000 in 1995, were ecstatic.

Betaseron was manufactured using recombinant DNA technology—interferon beta-1b is grown inside cultures of E. coli bacteria. It structurally differs from natural human interferon-beta: its amino acid sequence is slightly modified, and the protein is "non-glycosylated." The corporate brochures claimed a brilliant array of mechanisms: immunomodulation, shifting the T-cell response profile, suppressing pro-inflammatory cytokines, switching immune cells to a protective phenotype, and jamming the migration of activated lymphocytes across the blood-brain barrier. The patient had to manually inject this cocktail subcutaneously (under the skin) every other day. In the vast majority of cases, this routine triggered brutal side effects—a heavy flu-like syndrome, spiking fevers, severe chills, and localized skin necrosis at the injection sites.