Living Beyond the Diagnosis

It’s not easy being an optimist when you’re battling a disease like Multiple System Atrophy (MSA). But if you’re like me, you fight to keep hope alive. You try every therapy, explore every avenue, and wait anxiously for breakthroughs from the scientific community. Yet, here I sit, years after my diagnosis, still watching clinical trials stumble in the face of this cruel disease.

I’m not here to be negative, but rather to illuminate the frustrating reality we face as MSA warriors: the clinical trial landscape is a maze of dashed hopes and missed opportunities. Despite the courage of participants and the efforts of researchers, not a single treatment has yet emerged with statistically significant results to slow, halt, or reverse the progression of MSA. It’s a tragic quagmire that desperately needs attention—not just from scientists, but from policymakers, pharmaceutical companies, and the broader public.

The Challenge of MSA

As you know, MSA is a rare and devastating neurodegenerative disorder. It strikes indiscriminately, robbing us of motor skills, autonomy, and the ability to perform basic bodily functions. Unlike Parkinson’s disease, which shares some overlapping symptoms, MSA progresses rapidly and responds poorly to current treatments. This makes the need for effective interventions all the more urgent.

Yet, despite decades of effort, we remain without a single FDA-approved treatment. Why? Because MSA presents unique challenges to researchers:
• Its rarity makes it difficult to recruit enough participants for robust trials.
• The rapid progression of symptoms complicates study design.
• The disease’s heterogeneous nature means results often vary widely from patient to patient.

A Drug-by-Drug Breakdown

Let’s take a look at some of the most notable drugs that have gone through clinical trials for MSA. Each of these compounds once carried the hope of our community, only to fall short of expectations:

Riluzole

Originally approved for ALS, Riluzole was tested in MSA with the hope of extending survival and slowing progression. Unfortunately, the trials concluded with no significant benefits. Despite its neuroprotective properties, it became another dead end for our community.

Rasagiline

This MAO-B inhibitor, widely used in Parkinson’s, was thought to offer promise for MSA. However, clinical trials failed to show meaningful improvements in symptom management or disease progression. Rasagiline became another case of what might have been.
Minocycline
An antibiotic with anti-inflammatory properties, Minocycline garnered interest as a potential neuroprotective agent. Early trials offered a glimmer of hope, but larger studies ultimately dashed those hopes. It joins the growing list of treatments that simply couldn’t make the leap from theory to reality.

Therapeutic Plasma Exchange (TPE)

Some researchers have explored TPE as a way to remove harmful antibodies that might play a role in MSA’s progression. The results have been inconsistent, with no significant evidence to support widespread use. It’s another avenue that remains more question than answer.
As of January 2025, clinical trials for multiple system atrophy (MSA) have yielded mixed results regarding statistically significant outcomes.
Several clinical trials targeting multiple system atrophy (MSA) have been conducted by pharmaceutical companies such as Takeda (TAK), ONO Pharmaceutical, and Teva Pharmaceuticals. However, conclusive statistically significant results demonstrating efficacy in altering disease progression remain limited

ATH434 (Alterity Therapeutics): (By far the most accomplished trial, and yet, it’s had “limited success and tragically, it is not available through “Right to try” legislation)
In July 2024, interim data from a Phase 2 open-label study indicated that ATH434 was safe and showed improvements in disability and biomarker assessments after six months in MSA patients. Notably, 43% of participants experienced lowered scores on the Unified MSA Rating Scale (UMSARS), suggesting potential efficacy.

Verdiperstat (Biohaven Pharmaceuticals):

The M-STAR trial, a Phase 3 study evaluating verdiperstat’s effectiveness in slowing MSA progression, did not achieve its desired outcomes. The trial’s results, announced in late 2022, were disappointing, as the drug did not demonstrate the anticipated benefits.

Mesenchymal Stem Cell Therapy:

Research into the use of mesenchymal stem cells for treating MSA is ongoing. A study by the Mayo Clinic aims to assess the optimal dosing frequency, effectiveness, and safety of adipose-derived autologous mesenchymal stem cells delivered into the spinal fluid of MSA patients. While previous studies have suggested potential benefits, conclusive statistically significant results are yet to be established.

Takeda (TAK):

• TAK-341: Takeda initiated a Phase 2 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of TAK-341 in participants with MSA. The primary aim is to assess changes from baseline to Week 52 using the Unified Multiple System Atrophy Rating Scale (UMSARS) Part I. As of now, the study is active but not recruiting, and results have yet to be published.

ONO Pharmaceutical:

• ONO-2808: ONO Pharmaceutical is conducting a Phase 2 study to evaluate the safety, tolerability, pharmacokinetics, and potential effectiveness of multiple doses of ONO-2808 in patients with MSA. The trial is currently recruiting participants, and no results have been reported to date.

Teva Pharmaceuticals:

• TEV-56286 (Emrusolmin, Anle138b): Teva is sponsoring a multi-centered, double-blind, randomized, placebo-controlled Phase 2 study, known as TOPAS-MSA, to assess the efficacy and safety of TEV-56286 in treating patients with MSA. The trial is currently recruiting, and results are pending.

In summary, ATH434 have shown promising interim results, conclusive statistically significant outcomes from ALL MSA clinical trials remain limited. Research is ongoing, and the medical community continues to seek effective treatments for this challenging condition.

A Call for Change
If there’s a silver lining to this story, it’s the resilience of the MSA community. Every person who enrolls in a clinical trial is a hero. Their participation is what keeps the hope for a cure alive. But we need more than hope—we need action.

Here are some areas where I believe we can do better:

1. Increased Funding: MSA research is chronically underfunded. Rare diseases like ours often fall through the cracks of large-scale funding initiatives. We need to raise awareness and advocate for more investment in this field.
2. Better Trial Design: Trials must be tailored to the unique challenges of MSA, including smaller participant pools and faster disease progression. Adaptive trial designs and innovative biomarkers could be game-changers.
3. Collaboration Across Borders: The rarity of MSA means international collaboration is essential. We need more global studies and shared data to accelerate progress.
4. Compassionate Use Programs: For drugs that show promise but haven’t been fully approved (Like ATH434), compassionate use programs could offer some relief to patients while gathering valuable data.
   Staying Hopeful
   I’ll admit, it’s hard not to feel defeated at times. But I refuse to give up. I’ve seen the strength and determination of our community. I’ve experienced firsthand the courage it takes to try new treatments, even when the odds are stacked against us. And I believe—I have to believe—that a breakthrough is out there.
   To my fellow MSA warriors and our incredible support networks: Don’t lose hope. Keep advocating, keep fighting, and keep sharing your stories. The more attention we bring to MSA, the closer we come to a future where clinical trials in “MSA Clinical Trial’ville” aren’t a tragic quagmire but a beacon of hope.
   We deserve better. And together, we’ll demand it.
   ~Coach~