Below is information explain the importance and potential of using NfL. The web address for the full article is https://www.als.net/news/neing neurofilament-light-chain/’#:~:text=Because%20NfL%20is%20a%20structural,biomarker%20in%20ALS%20clinical%20trials.

“<strong style=”background-color: var(–bb-content-background-color); font-family: inherit; font-size: inherit; color: var(–bb-body-text-color);”>Neurofilament light chain (NfL) is a member of a family of proteins called neurofilaments that contribute to the structure of neurons in the brain and spinal cord. Research has shown that when neurons experience injury or damage, these proteins are shed and find their way into the <strong style=”background-color: var(–bb-content-background-color); font-family: inherit; font-size: inherit; color: var(–bb-body-text-color);”>cerebrospinal fluid (CSF) and bloodstream. While even healthy neurons shed a certain amount of NfL, elevated levels of the protein in blood or CSF are associated with several conditions that affect the central nervous system.

This has made NfL attractive to researchers as a potential biomarker in several diseases – including amyotrophic lateral sclerosis (ALS). A biomarker is a kind of biological “fingerprint” – something measurable about a living thing that can provide doctors or scientists with information about that organism. Biomarkers have many potential functions in diseases, including:

• Helping doctors diagnose a disease
• Measuring the progression of a disease
• Helping researchers see whether a drug has reached its intended target in the body
• Providing evidence that a drug is changing the course of a disease

Some common biomarkers associated with diseases include blood glucose levels for diabetes or LDL cholesterol for heart disease.

A lack of reliable biomarkers for ALS is one of the biggest challenges in this disease. For example, ALS diagnosis is based on the clinical presentation of symptoms combined with tests like EMGs, while eliminating other possible diagnoses. There is also much interest in developing and using biomarkers as surrogate endpoints in clinical trials. To date, ALS trials have generally relied on measuring a person’s survival, which can lead to lengthy trials, or changes in motor function through the ASLFRS-r survey, which has been criticized for not being sensitive or completely objective. As a surrogate endpoint, a biomarker would be used to show that a drug is having a reasonably likely effect on a disease.

The Potential of NfL in ALS

NfL is often called a nonspecific biomarker because it can increase not only in ALS, but in many other conditions, including traumatic brain injuries, multiple sclerosis, and Alzheimer’s disease. Because of this, NfL has limited potential as a diagnostic biomarker for ALS. However, an observed increase in the level of blood NfL has been found to be a potential indicator of the onset of ALS symptoms for people with ALS-related genetic mutations. It is showing promise as a biomarker for risk of onset of the disease in that subpopulation.

The level of NfL in the blood and CSF at diagnosis has been shown to correlate with the speed and severity of ALS progression, which has indicated that it may be a prognostic biomarker for ALS. While all people with ALS appear to have some degree of elevated NfL in earlier stages of the disease, those with higher NfL levels early on have been found to experience faster disease progression than those with lower NfL levels.

NfL in Clinical Trials

Currently, researchers are also focused on NfL’s potential as a biomarker of drug response in clinical trials. Because NfL is a structural component of neurons that is released when they are damaged, an experimental treatment that decreases levels of NfL in a clinical trial could indicate a possible slowing in neurodegeneration. This means that NfL has potential as a surrogate biomarker in ALS clinical trials.

In one recent case, Qalsody, a treatment for SOD1-related genetic ALS, was granted accelerated approval based on results demonstrating lowered levels of blood NfL in trial participants. A second trial of the drug for asymptomatic carriers of fast progressing SOD1 mutations is currently ongoing. This trial is also following participants’ NfL levels, in this case to determine when to start dosing the drug. A rise in NfL levels in asymptomatic carriers could indicate that the onset of weakness is likely approaching in the next 6-12 months. By administering the drug at this early time, researchers hope to delay the disease onset.

als.net

ALS Therapy Development Institute

ALS TDI

My biggest area of concern is my breathing. In Sept/October I was having difficulting saying a sentence without having to stop and catch my breath. When I was walking I was out of breath long before I was physically tired. My forced vital capacity dropped from the 80s to low 30s in what seemed to be overnight. Perhaps it was over a week or two, but it was quick and scary! In October my FVC was mid 30s, in January 39/40ish. Last week it was 43!! I still cannot walk and talk at the same time without getting out of breath, but I can speak much better and my breathing is less challenging. Also, at my January visit when they did the neuro exam – ALL my scores for muscle strength improved. ALL of them! I’m still not back to my pre-ALS self, and they have told me that will not happen. I’ll never be 100%; and I’m ok with that. I know that being eligible for Tofersen gives me hope and I am grateful for the hope and the improvements. They also said I can expect to see more improvements as time goes on.

Please understand that it is still obvious that I have ALS. I’ve fallen or tipped over a few times at work and needed help getting back on my feet. I’m slow and I don’t do as much public speaking as I use to do. However, I’m over a year into this journey and I’m still working, living independently, and enjoying most things. That’s a win in my book. That’s a win in OUR book!

I’ve had conversations with one of the doctors about my breathing. I was declining so quickly, over 50 points in less than a month. There isn’t enough room to have another drop like that. I’m convinced, and so is my doctor, that had I not started Tofersen in July, I would not have made it past Sept/October. I don’t say that to be morbid or negative; just the opposite. I’m a realist and I was preparing for what could happen. (paperwork, etc) I’m the first case in my family that has had ALS impact their diaphragm this early on. (I’m the 15th or 16th person in my family to have ALS…can’t keep up anymore). Typically, this is the last thing to happen. Let me also add that I am single and have no children. For anyone in my position, I’m sure you can understand the added stress of being in my shoes and the great need to be prepared. Every situation has it’s advantages and disadvantages. I just enjoy the advantages and do my best to prepare for any possibilities in my future.

I focus and try very hard to maintain a positive attitude. I focus on what I can do, and enjoy the memories of what I was lucky enough to do. I will share that when I was diagnosed I did ask for an anti-anxiety med. My doctor prescribed a med that works for both anxiety and depression. I think that it is only natural to experience a wide range of emotions – grief especially when you are facing a life altering diagnosis such as ALS. I’ve never been one to reach for prescription therapy, but I work in the mental health field and I know that when it’s needed, it is a game changer for many. So, I am trying to practice what I preach. This isn’t information I share with people outside of our circle. Mainly because it doesn’t come up. I also use a bipap machine nightly and often during the day when I get home from work. Dr. Granit said that was the best thing I could do to help with my breathing! I have no issues using it because I feel so much better when I do. I get a good night’s sleep – and I think it helps my body to recover.

I had an EMG on Friday and it showed where some nerves were spreading out to compensate for damaged nerves. That was pretty cool to hear. It didn’t seem to show any new damage since last fall from what I understood.

So, overall Tofersen is doing wonders for me. I am so grateful for all of you, the doctors, researchers and volunteers for the clinical trials. We all know that rare diseases do not get the same amount of attention and funding as other diseases. I am one of the few, the fortunate pALS that has the SOD1 mutation (I never thought I’d say that) that makes me a candidate for Tofersen. I don’t take this for granted for a second.

Please know that I am an open book and will happily talk to anyone on our forums or in our ALS Community about Tofersen and my journey. I will continue to advocate and support our community. Know that you can reach out to me with any questions or concerns and I will respond. If you don’t hear from me it is an oversight and just send me a private message.

There is research currently being conducted to find similar treatments for other mutations. I know that the C9orf mutation is a focus for much of this research. The technology is amazing, life altering and brings hope to our community. I believe that we are the generation that will continue to see treatments discovered that will make ALS a livable disease; hopefully a curable disease.

Cheers!

Amanda Sifford

I live in Florida and I get my treatments at the University of Miami ALS clinic. I live in the Fort Myers area. I just found out that someone that lives in my area also has the same mutation and has started his treatments here in Fort Myers!! What a small world.

The treatments should be available anywhere in the US. If you need names or phone numbers just let me know. Biogen has patient advocates that will help get you set up and help with the insurance approval.

I had been taking it prior to it being approved getting it from a compounding pharmacy then switching over to CVS Caremark once it was approved. I will say that at my last 2 clinic appointments that I haven’t lost any points on the ALS/FRS scale. In fact I gained 2 points. Is it from the medication combination that I’ve been taking or is it interpretation from the clinicians that are adding up the score from my answers. I don’t know.

I spoke with my neurologist when the failure of Relyvrio was made known. He wants to read the whole report before making a recommendation. He said that it was my choice if I wanted to continue to take it while it was still available or stop it. I have just received a refill yesterday so I’ll finish this month and then go back to taking Tudca.

Amylyx Pharmaceuticals Announces Topline Results From Global Phase 3 PHOENIX Trial of AMX0035 in ALS | Amylyx Pharmaceuticals, Inc.

https://www.ferrer.com/en/results-study-ADORE-ALS

As we speak about Edavarone, I would like to know what is the difference about Radicave and ADORE as it is as well Edavarone. Radicava holds 105mg / ADORE used 100mg. I have just seen a statement from the producer of Radicava (https://www.mt-pharma-america.com/media/news/press-releases/2024/01/17/mitsubishi-tanabe-pharma-america-inc-mtpa-statement-on-ferrers-phase-3-adore-clinical-trial-of-fnp122-fab122).

I think the patients should get more details about it. What is your opinion?

https://www.ferrer.com/en/results-study-ADORE-ALS

As we speak about Edavarone, I would like to know what is the difference about Radicave and ADORE as it is as well Edavarone. Radicava holds 105mg / ADORE used 100mg. I have just seen a statement from the producer of Radicava (https://www.mt-pharma-america.com/media/news/press-releases/2024/01/17/mitsubishi-tanabe-pharma-america-inc-mtpa-statement-on-ferrers-phase-3-adore-clinical-trial-of-fnp122-fab122).

I think the patients should get more details about it. What is your opinion?

RE: hypermetabolism – – “normal” or non-ALS patients burn calories at a predicted rate. With ALS- hypermetabolism… the muscles are burning calories at a higher rate.