Anyone have experience with Multiple System Atrophy (MSA)?

My pronunciation gets worse the more tired I am.

@scottmoon
Yes, I've found that true for me as well. Fatigue tends to worsen the symptoms of neurological problems. One thing I learned from speech therapy is the value of reading aloud. It really does help. You might try it and see if it helps.

@shelleystolfi You have my belated deepest condolences for your loss! i understand the struggles Joe went through, and, as his caregiver, you went through so much yourself! Take care! 🌹

Last year I was diagnosed with PKD but I was also told I have MSA. Multiple system Atrophy.
Are there others in the group with MSA? What’s been your experience with it?

@itzamike26 - just wanted you to know I moved your post to this existing discussion about multiple system atrophy:

- Anyone have experience with Multiple System Atrophy (MSA)? https://connect.mayoclinic.org/discussion/multiple-system-atrophy-1/

Hoping members here such as @foundryrat743 @scottmoon @saganjames and many others will chime in to tell you about their experiences with MSA and how things have gone for them.

Just to clarify, since there are so many acronyms in medicine, about your diagnosis with PKD. Will you share more about what that stands for? Also, are there any symptoms that have been particularly bothersome for you lately?

I have MSA Type-C. Here Are Some of my symptoms.
Trouble with movement and coordination. This includes loss of balance and not being able to walk at all anymore. I've progressed from a walker to a wheelchair.
Slurred, slow or soft speech, known as dysarthria.
Changes in vision. This may include blurred or double vision and not being able to focus the eyes.
Constipation.
Loss of bladder or bowel control, known as incontinence.
Produce less sweat.
Trouble controlling emotions, such as laughing or crying when not expected.
Orthostatic hypotension is a form of low blood pressure. I take medicine to increase my BP.
Loss of fine motor control. Hard to write or type.
I also have Peripheral neuropathy.

I have posted this before re: MSA clinical trials. I don't have this malady, just want to help.

Here are the key ongoing and recent clinical trials and therapeutic candidates:
Top Clinical Trial Candidates (2025–2026)
• Amlenetug (Lu AF82422 / Lundbeck): This is a human monoclonal antibody designed to bind to
-synuclein and inhibit its aggregation.
o Status: A Phase 3 trial, MASCOT (NCT06706622), was initiated in late 2024/early 2025 following positive results from the Phase 2 AMULET trial. It was granted FDA Fast Track designation in February 2025.
• Emrusolmin (TEV-56286 / MODAG / Teva): A small molecule designed to target -synuclein oligomers.
o Status: In Phase 2 development (TOPAS-MSA study). It was granted FDA Fast Track and Orphan Drug designation in September 2025.
• ATH434 (Alterity Therapeutics): An oral iron-targeting agent designed to reduce iron-induced
-synuclein aggregation in the brain.
o Status: Reported positive Phase 2 results in early 2025, demonstrating reduced brain atrophy.
• AB-1005 (AskBio / Bayer): An investigational gene therapy (AAV2-GDNF) delivered to the brain to promote the survival of dopaminergic neurons.
o Status: Completed enrollment for the Phase 1 REGENERATE MSA-101 trial in September 2025.
• Ampreloxetine (Theravance Biopharma): A norepinephrine reuptake inhibitor focusing on symptomatic treatment of neurogenic orthostatic hypotension (nOH) in MSA.
o Status: Active, but reported in March 2026 that the Phase 3 CYPRESS study did not meet its primary endpoint.
• ION464 (Ionis Pharmaceuticals): An antisense oligonucleotide (ASO) designed to prevent the production of -synuclein protein.
AskBio +10
Key Areas of Investigation
•
-Synuclein Reduction: Antibodies (amlenetug) or small molecules (emrusolmin) to clear toxic protein buildup.
• Neuroprotection/Iron Regulation: Agents like ATH434 to prevent brain atrophy.
• Gene Therapy: Using GDNF to protect cells.
• Symptomatic Management: Treating debilitating orthostatic hypotension (e.g., ampreloxetine).
• Natural History Studies: Studies such as TRACK-MSA (NCT04450992) are ongoing to identify better outcome measures for future trials.
NYU Grossman School of Medicine +3
Recent Trial Outcomes
• Sirolimus: A study supported by the NIH was ended early after interim analysis indicated it was not effective in slowing MSA progression.
• Trial Challenges: The rapid progression of MSA makes trial recruitment and retention challenging, with a high failure rate for neuroprotective compounds.
Regards,
Sagan