Experimental Antisense Trial is Showing Promise for CHCHD10-ALS

When NextGen ALS was started in 2021, the goal from the very beginning was always to provide hope for those whose lives had been devastated by genetic forms of ALS.  At it’s core, ALS is a terrible disease, but for families with genetic forms of ALS you have to watch as it destroys the lives of your parents, cousins, brothers and sisters, and sometimes even your own children.

From Then to Now

From the very beginning, our mission was to fund research for targeted and directed treatments, focusing on ASO’s (Antisense Oligonucleotides).  ASO’s are a genetically targeted treatment option for neurodegenerative disease types like Alzheimer’s, Parkinson’s, and ALS.  When we started our mission, we began by focusing on this treatment option for CHCHD10-ALS.  

Starting in 2021, a lot of effort was put into the initial mechanistic studies and ASO development at Weil Cornell Medicine and Ionis Pharmaceuticals.  The subsequent years were spent doing Petri dish studies and animal testing to measure the safety and effectiveness of the treatment in a controlled environment.

What’s Happening Now

In May of 2024, the first CHCHD10 ASO injection was administered in experimental human trials.  The human trial, which is being overseen by Dr. Neil Schneider, is being administered from Columbia University’s Department of Neurology in New York.  

Since that time, every person from the core group of nine trial participants has had at least one injection of this new experimental treatment, and most individuals have had the treatment administered multiple times.

How it Works

Human trials have very strict requirements for the participants, so all treatments have to be administered from certified and approved facilities, with most being done at Columbia University in New York.  Additionally, the administering of the treatment has to be done following strict protocol, which ensures a high level of consistency as a baseline for the results of the study.

The study is currently hosting nine carriers of the CHCHD10-ALS gene deformity. For these individuals, the ASO is injected into the spinal column, beginning with an initial dosing phase.  Over time they will settle into a regularly scheduled treatment every 3 months.  Initially, dosage amounts were started at smaller doses, and are being incrementally increased based on results and individual patient’s ability to tolerate the treatment.

What We’re Seeing and Hoping For

It’s difficult to report real results this early in a study, especially because CHCHD10-ALS is not an aggressively fast moving form of ALS, so testing for the physical symptoms will take some time.  There are; however, certain biological markers that we can test for to determine whether the treatment is having a positive effect.  The most commonly tested bio-marker is a protein in the blood called NfL (neurofilament light). Scientific historical data tells us that when NfL levels are high, it is an indicator that neurons are damaged or deteriorating, so when we read lower NfL levels, we can assume a decrease in ALS progression.  

Initial test results thus far have shown decreases in these NfL levels, which shows great promise for the treatment moving forward.  There have also been zero adverse reactions or negative physical effects of the treatment on any of the experimental trial participants, which indicates a high level of safety and tolerability for the treatment.

We’ve seen similar results in another FDA approved ASO treatment called Qalsody, which targets a different genetic form of ALS called SOD1.  ALS FRS (Functional Rating Scale) scores from the SOD1 treatment study have shown results in several participants that indicate a complete halt in progression of the disease.  Additionally, recent information has shown promise for many people with genetic forms of ALS that they may even be able to regain some of the function that they had lost, which was believed by much of the ALS research community to be highly unlikely.

Based on initial results from the CHCHD10-ALS experimental trial, it is our hope that this treatment will yield similar results, and serve as an additional example of the effectiveness of targeted treatments like ASO’s for neurodegenerative diseases.

Real Hope for Families with ALS

For families with genetic forms of ALS, like the Weber family, results like this are not only life changing, but they’re the first real sign of hope they’ve ever had.  Looking back at the Weber family genealogy, we identified nearly 100 people whose lives were likely taken by ALS over the past five generations, and their family is still being devastated by the disease to this day. 

Cathy Kettner is one of the nine siblings in the Weber family, and for her, this type of data shows promise for the future generations of their family.  “When we started this research, our intent was to save our children from the devastation of ALS that our family has had to succumb to,” Cathy says.  “Being a mother, our worst fear is not being able to protect our children… but how do you protect your children against a terminal disease?  Until now, there has not been a way to protect our kids from this disease.  This treatment gives us hope that our children will see a life… a full life… that isn’t ravaged by the devastation ALS can cause.”

It is our hope that treatments like this will change the landscape for all types of families with genetic forms of ALS, providing real hope… hope that until now was so far off that it almost felt like a dream.  But now, there’s finally hope that the dream could be a reality.