Living Beyond the Diagnosis

As I sit down to write this, my fingers tremble not just from the symptoms of my illness, but from the weight of disappointment that has settled upon me and my fellow MSA Warriors in this battle against Multiple System Atrophy (MSA). MSA, a cruel and relentless disease, that robs us of our mobility, our autonomy, and ultimately, our lives. It’s a terminal diagnosis, one for which there is currently no cure. But in the midst of this darkness, we cling to the flicker of hope provided by ongoing clinical trials, praying for a breakthrough that will offer us even a sliver of reprieve from this relentless onslaught.

However, the reality is often far from hopeful. Each trial brings with it a cocktail of anticipation and anxiety, only to be met with disappointment and despair as we witness the lack of statistically relevant results. Our hopes rise and fall with each update, each email that brings news of yet another setback. Allow me to dissect these trials, each a beacon of hope overshadowed by the stark reality of our condition:

AAV2-BDNF Gene Therapy – March 26^th 2024 – This trial, offering the promise of gene therapy, seemed like a beacon of hope amidst the darkness. But we received this via email: “Thank you for contacting us about the BDNF gene therapy trial. Unfortunately, individuals of diagnosis other than Alzheimer’s Disease are not eligible to participate in this study and at this time we are not expanding this study to individuals with Parkinsonism. Thank you for your interest and reaching out.”

Anle138b-Teva – Jan 30^th 2024 – Despite our anticipation, we received no information regarding the initiation of any studies with this investigational agent.  We did receive this via email: “This letter is in response to your request for information regarding the clinical study for Anle138b.  Thank you for your continued interest in Teva and our clinical development program.   We still do not have any information regarding the initiation of any studies with this investigational agent, nor where the study sites may be the U.S.” * Note: As of May 1st 2024, we are seeing signs that this trial May start soon.

ATH-434 – May 1^st 2024 – Still clinging to hope here. We received this via email: “The ATH434 trials are still in process.  Alterity has given a preliminary timeframe for the next step as 1^stQ 2025.  We will keep you updated when we know more.”

BHV-3241– https://clinicaltrials.gov/study/NCT03952806 With no results found of statistical relevance, this trial adds to the litany of disappointments that we have faced. It’s yet another reminder of the uphill battle we face in our quest for a cure.

ION-464 – March 4^th 2024 – This was the email response to our inquiry: “As a reminder, this study will not be opening any study centers in the United States and cross border travel outside the US is prohibited for this study.” The exclusion of study centers in the United States dealt a heavy blow to our hopes, leaving us stranded on the sidelines as we continue the search for answers.

KM-819 – March 4^th 2024 – Yet another disappointing email response: “The trial is ongoing in Korea, and we are planning to do in US in the future.  However, we have not decided when.  Once we decide, I will let you know.”

Lu AF82422 – March 5^th 2024 – Via email: “called the AMULET trial, tested Lu AF82422 on MSA patients. Overall, the study showed some promising results in slowing down the progression of MSA symptoms compared to the placebo, although the difference wasn’t big enough to be statistically significant. Overall, this study suggests that Lu AF82422 might be a potential treatment option for MSA patients, but more research is needed to confirm its effectiveness.” “In short, they did not find a significant effect on their primary measure (change in UMSARS score from baseline), but they report “signals of efficacy across other clinical and biomarker endpoints.”

*ONO-2808 – https://clinicaltrials.gov/study/NCT05923866 *Still evaluating this Phase 2 trial, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Efficacy of Multiple Doses of ONO-2808 in Patients With Multiple System Atrophy (MSA).

*TAK-341– https://clinicaltrials.gov/study/NCT05526391 *Still evaluating this Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous TAK-341 in Subjects With Multiple System Atrophy. Shows as “Recruiting”, but no locations have started yet.

*While these trials hold promise, the lack of concrete progress leaves us teetering on the edge, wondering if we’ll ever see the light at the end of this long and arduous tunnel.

**UB-312 – https://clinicaltrials.gov/study/NCT05634876 * This is a Phase 1b study to determine the safety, tolerability, and immunogenicity of UB-312 in participants with multiple system atrophy (MSA), and in participants with Parkinson’s disease (PD). UB-312 is a UBITh®-enhanced synthetic peptide-based vaccine and may provide an active immunotherapy option for treating synucleinopathies including the most prevalent form, PD; and the most rapidly progressive form, MSA.

**GDNF Gene Therapy – https://clinicaltrials.gov/study/NCT04680065 *Highly invasive, Experimental: Active Treatment – Biological: AAV2-GDNF gene therapy Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose OR Sham Comparator: Placebo Surgery – Procedure: Sham (Placebo) Surgery Bilateral partial burr/twist holes without dural penetration. No results to share as of yet.

** While both hold potential, the former in providing active immunotherapy and the latter in gene therapy, the lack of conclusive results leaves us uncertain and uncomfortable.

In the face of such disappointment, a new ray of hope has emerged:

It’s called MyTrial, a program from Khurana Labs that utilizes the infrastructure of the Harvard Biomarkers Study (HBS 2.0) and the Movement Disorders Genetics Clinic at Brigham and Women’s Hospital. As one of the 20 MSA patients participating in this groundbreaking research, I find solace in the hope that this unique approach offers.

MyTrial collects samples like skin biopsies to create personalized stem-cell models, enabling researchers to study the disease and test drugs to find the best treatment for each patient. The program also uses a unique approach called the “n-of-few” clinical trial approach. This means they introduce drugs to patients based on their medical history and biomarkers they’ve collected over time. By testing drugs on the patient’s own brain cells in the lab first, they hope to improve the success rate of clinical trials.

Picture your damaged neurons in a group of Petri Dishes, being introduced to all the current drugs above, plus the new experimental ones not yet approved by the FDA and others. They can be tested in days or weeks, not a year like the trials are now. Saving MSA patients years of failure, like the ones they are experiencing with the current trials. After all, time is not on our side. 😉

As I embark on this journey, I carry with me the hopes and dreams of my fellow MSA Warriors in this battle against MSA. Together, we cling to the fragile threads of hope that this new avenue of research offers, praying for a breakthrough that will offer us the respite we so desperately seek. Until then, we stand united in our fight, refusing to surrender to the despair that threatens to engulf us. For in the darkness of despair, we find the strength to persevere, fueled by the flicker of hope that burns brightly within each of us.

Stay tuned to this blog for updates and to follow along as I go through this craziness. 😊 Adventure begins in 1 week! May 15th 2024. Boston here we come!

~Coach~