Reasons for Hope in ALS Research with the Discovery of NU-9

Neuron

In a study funded in part by The ALS Association’s TREAT ALS program, researchers from Northwestern University have identified the first compound (NU-9) that eliminates the ongoing degeneration of diseased upper motor neurons, a key contributor to ALS. While this news is exciting, this study has only tested the compound in mice and in laboratory neurons and is in the very early stages. Researchers must now determine if this particular compound can be further developed for humans and would need to do additional chemistry to optimize the compound. In addition, assessments are needed to determine whether this compound can get into the brain and spinal cord at appreciable levels, engage with its target and if it is safe and tolerable. Although still early in its development, we are encouraged by the addition of another therapeutic intervention in the ALS drug discovery pipeline and are happy that our funding was able to seed this line of research work.  

In a recent Connecting ALS podcast, Dr. Kuldip Dave, vice president of research for The ALS Association, talked about these new findings and the hope they bring to the ALS community and global research collaboration. A portion of that conversation has been edited and condensed below.

ALS research has been making headlines since we turned the calendar into 2021. And one of the more exciting developments is related to a paper published in Clinical and Translational Medicine, describing how researchers at Northwestern reported that they identified a compound that eliminated degeneration of motor neurons that are connected to the development of ALS. What have you heard about this development and what can you tell us about research into the compound known as NU-9?
We're very excited to see these findings published. Let's first talk about the project itself before we talk about NU-9. The ALS association supported Dr. Ozdinler and her team at Northwestern University a few years ago through the funds raised during the Ice Bucket Challenge. And the goal of the project was to find out the protein landscape of healthy and vulnerable, motor neurons in two different stages of the disease. So, what do I mean by that? We know that in ALS we have neurons, which are brain cells that are sick and dying, and we have neurons that are fine and healthy. And we know that those are unhealthy sick neurons, things start to dysfunction. And Dr. Ozdinler wanted to see what proteins are changing in neurons that are sick versus neurons that are fine and healthy.

In other words, can changes in protein landscape lead to neurons being more vulnerable to cell death. And why is this important? Because if we can find those proteins that are specific to unhealthy neurons, then those can serve as markers to tell us something bad is going on, or they can serve to identify new therapeutic targets for us. For example, if we know certain protein is dysfunctional, then we can make drugs against that cookie.

The other reason why Dr. Ozdinler’s work that you mentioned, that was published in Clinical and Translational Medicine, why it is so relevant is that it was focusing on upper motor neurons. So, what are upper motor neurons? These neurons take signals from the brain and transmit them to the spinal cord so that movement can happen. So, they're very, very important in ALS.

And we know that these upper motor neurons get sick, degenerate and die in ALS. So this was the rationale for our funding a few years back for this study, and the results of that funding was that her team found that there were certain proteins and protein function that was changed in two very specific cellular structures: the mitochondria, which is the energy producer of our cells; and this other cellular structure called ER or endoplasmic reticulum. I know that's a big, big word, which is involved in making new proteins and folding them the right way.

So how did they, how did they find this drug? Researchers at Northwestern University screened and tested over 50,000 compounds. And then they did multiple rounds of optimizing the chemistry, and that's how they got this compound, NU-9. Now, remember I told you that they found protein changes in upper motor neurons in two different areas, mitochondria and the ER? They tested this compound, NU-9, in cells and in animals and found that the drug improved the structural integrity of those two structures, the mitochondria and ER. The drug kind of stabilized cell death, and in fact – and this was really significant – reversed some of the pathology, the bad stuff that was going on, essentially making sick neurons healthy again. And in mice, it also improved motor function. So, this is really very, very exciting.

Where are we now in terms of what we know about NU-9? What are the next steps between today and having something that is marketable and available for people with ALS?
Hope is a big thing in ALS. When we see good data, positive results like this, there is certainly going to be a lot of excitement, but there are a couple of things we should keep in mind here in terms of the timeline. This research was conducted on mouse models, and there are a few steps that still need to happen. These are early results. They already have a lot of information collected on the drug: where it acts, whether it enters the brain, how long does it stay in the brain, these are the things we call PK or pharmacokinetics of the drug. It's great that they have this information.

Now they need to make sure that the chemistry of the compound is such that it can be given to humans. They would also need to make sure that the drug is safe and tolerable, and generally that is done in two different species of animals. And once they have that data, they can then submit a package to the FDA to ask to do a clinical trial. And when the FDA looks at the data package and grants them a go ahead, that is when they can start to test the treatment in humans for safety and efficacy.

To listen to the entire interview with Dr. Dave, “Finding Hope on the Horizon Through ALS Research…” on Connecting ALS, visit ConnectingALS.org HERE.

Comments

Submitted by: Randy T. on Sun, 03/21/2021

My husband was diagnosed in late October early November of 2020 with ALS! He would absolutely want to be apart of the NU9 drug clinical trial! Please contact us! We read about Northwestern University research !

Submitted by: Robert K. on Fri, 04/02/2021

I was diagnosed with ALS in Aug 2020. I welcome the opportunity to take part in the NU-9 clinical tests.

Submitted by: sherry S. on Sun, 04/25/2021

I would like to be in the study

Submitted by: Jill L. on Wed, 04/07/2021

I was diagnosed with Bulbar ALS in July 2020 ! This would be life changing for me please contact me when you are ready for your study
💕🙏!

Submitted by: Mark N. on Mon, 03/22/2021

I was diagnosed with Sporadic ALS in May 2014. I have slow progression, but I’m hanging on by a limb to prevent the final stage that will cause me to be on a feeding tube and ventilator. I need a treatment soon or I will be faced with decisions that will be dyer. I know Im not alone. We all need this to be pushed through quickly and receive orphan drug approval status. I want to put my name in the hat to test this. I don’t care if I’m the first human. I do well with treatments, and am still healthy to participate. Compassionate drug use is what we all want. I researched this NU-9 compound and the research results on ALS mice and it looks very promising for humans. Very promising results to us, is something we need to try now. Compassion & Speed is what we are hoping and praying for. You have ALS patients that like me and others that will climb on board at anytime or place to be apart of a cure. Its our legacy! To help change this for those diagnosed that follow us. Thanks in advance for all that your doing to end this disease.
Sincerely, Mark Nance 🔥

Submitted by: Teila M. on Tue, 03/30/2021

How do I participate in the test with NU-9?
For the treatment of amyotrophic lateral sclerosis.

Submitted by: John H. on Thu, 04/01/2021

Thank you for the research that gives us with ALS hope. Please accelerate your program if possible due to our rapid decline. Please contact me when the clinical trials start, I would like to have an opportunity to participate.
Living with Lou is our greatest challenge!

Submitted by: Charles J. on Thu, 04/01/2021

This is very exciting and positive news for those currently diagnosed with ALS. My mother passed away January 2020 with ALS. My heart and prayers goes out to each and everyone of you that solutions will become available to those who have been diagnosed with this disease.
Sincerely, Charles Jean-Baptiste II

Submitted by: James H. on Thu, 04/01/2021

I would like to participate in your trial. I have PLS and was diagnosed in 2013.

Submitted by: James H. on Thu, 04/01/2021

I live about 75 miles from Northwestern. I was diagnosed with ALS in 2013 but had symptoms well before, like 2005.

Submitted by: Dixie D. on Thu, 04/01/2021

I helped care for my aunt in her home as she declined from ALS. She died in 2015 at age 87. She was diagnosed just 4 months before her death. We were told hers was the "bulbar" type (sp?), as she quickly became unable to speak or to swallow. I hope this N.U. study will soon lead go a clinical trial for all those now coping with ALS and for all those who will yet be diagnosed.

Submitted by: Naresh C. on Thu, 04/01/2021

I was diagnosed with PLS almost 12 years ago, and I have worked through my challenges so far. NU 9 seems ideally suited for this disease since in PLS the UMN are predominantly targeted. When you open up the human trials, kindly reach out to me.

Submitted by: Patty M. on Fri, 04/02/2021

I was diagnosed with ALS January 2021, I’m still trying to accept my new life & having a hard time. I pray that this new breakthrough will work & save us from this dreadful disease.

Submitted by: Julio F. on Fri, 04/02/2021

I have to participate in the test with NU-9, please call me asap is available I have ALS since 2012

Submitted by: Patty M. on Fri, 04/02/2021

I was diagnosed with ALS January 2021, & I’m having a difficult time accepting my new life. I pray this new development is the answer we need to save our lives.

Submitted by: Julio F. on Fri, 04/02/2021

I like participate in the test with NU-9, please call me

Submitted by: Carole M. on Fri, 04/02/2021

I was officially diagnosed October, 2019, but was symptomatic from 2013. i would like to be included in any trials for which I am suited.

Submitted by: Tim G. on Fri, 04/02/2021

Great news and amazing medical progress. We pray for and support acceleration to human clinical trials as soon as possible. Much like the sense of urgency to address COVID-19, we need the same warp speed progress for our family and friends that are "living with Lou".

God speed and thank you.

Submitted by: Panela M. on Fri, 04/02/2021

I was diagnosed with ALS March of 2020. I have been dealing with symptoms since March of 2019. Like all the rest I want to urge the treatment of Nu-9 for humans. If there is anyway we can speed this process along, please share. I know there is support for that. I can feel the progression in my lower spine. I want to be apart of any upcoming trial with this. I looked at the clinical trials and saw none related to Nu-9. Please please put all of us on a list to help combat this horrifying disease.

Submitted by: Pamela M. on Fri, 04/02/2021

I have had ALS since March 2019. Like all those before me I want to be in the trial. We all need hope and are willing to do anything to speed up the process of getting the Nu-9 drug for humans. Please please please sign us all up for a clinical trial. We are willing to be guinea pigs for any hope at all. I tried to sign up on the link provided but nothing is there. What can we do to push this forward?

Submitted by: Rebecca D. on Sat, 04/03/2021

My husband has had ALS for 14 years. If this new drug goes into human trails, my husband is the one to study. He had been turned down for other studies because they day he has had it to long. We think he is the one that should be studied because the question is "WHY"had he survived so long with this horrible disease. He is loosing the use of his hands more and more every day. Also, he is getting more muscle spasms then normal. But he is a fighter. He still works on cars, all kinds of outdoor and indoor projects we have around the house like he doesn't have this disease. Please he would be the perfect candidate if this drug goes to human trials.

Thank you for your time.

Submitted by: vernon N. on Sat, 04/03/2021

I was diagnosed day before thanksgiving in 2009 with ALS. My motor skills have declined over the year's. If NU9 could give some control back to us that would be a Blessing . I would like to be part of the human trill if I could be of help.

Submitted by: priscilla W. on Sat, 04/03/2021

I was diagnosed 6 months ago but have had symptoms for the last 2 years. I would happily be part of any clinical trial of NU-9. This disease puts us all in a desperate situation. Thank you for your research and for hope!

Submitted by: Lucile D. on Thu, 04/08/2021

I would like to be part of any study

Submitted by: Kamau N. on Thu, 04/08/2021

I am sure that the compound is a game changer. I was first diagnosed in 2010 but had symptoms from 2006. I would like to be able to be part of the human trials

Submitted by: John D. on Fri, 04/09/2021

I had symptoms for a while. Finally went to the Cleveland Clinic where I was diagnosed with early stage ALS in March 2021. I’d rather do more than just take unaffordable meds to slow the disease a tiny bit. Even with the uncontrollable crying I haven’t lost my sense of humor. I’d buy a van and live in it down by the river to be close to Northwestern. I’m serious. Please sign me up for the NU-9 trials if it becomes available before my time is up.

Submitted by: Joy J. on Sat, 04/10/2021

My sister died of ALS 20 years ago. Since then, I’ve done what I can to raise money for ALS research. I recently raised $30,000 which went to the ALS Association for research by bicycling all of Route 66. It’s so good to hear that progress is being made. We need more breakthroughs and fast! This disease is a heartbreaker and we need to find the cure as quickly as possible.

Submitted by: Maurice S. on Tue, 04/20/2021

IF NU9 is safe, why must one wait a year to start studies? Is there not a "right to try" law that will allow one to take it sooner for compassionate need? Many patients cannot wait and will be moribund or dead before trials begin.

Submitted by: Amy L. on Wed, 04/21/2021

This study has only tested the compound in mice and in laboratory neurons and is in the very early stages. Researchers must now determine if this particular compound can be further developed for humans.

Submitted by: Tom K. on Fri, 04/30/2021

I have ALS was diagnosed in 2019 still doing fairly well but I would love to try nu-9 Compound on a clinical trial when it becomes available the sooner the better it is all a matter of time And time is precious with people with ALS so the sooner the better I know there is a Risk but it will not make a lot of difference in a few years hopefully let’s try it On a few people that volunteer for it and ICan be one of them thanks

Submitted by: Rex L. on Wed, 05/05/2021

I was diagnosed in 2019 and my progression has been slow to this point, but I can feel the transformation taking place throughout my body. I would love to be considered for this trial. My wife has MS so it is imperative that I get better so I can help her.

Submitted by: John O. D. on Fri, 05/07/2021

I would love to be in the 1st phase trials for NU-9 ,it would be a huge Blessing

Submitted by: Silvia B. on Thu, 05/13/2021

I was disgnosticated with ALS january 2021. Plesse..I would like to particioate in the clinical trial of NU-9. I am 57 years old.

Submitted by: Ruhan K. on Wed, 05/19/2021

This is amazing, finally some hope.
I was diagnosed with als in 2018 and would like to be part of the clinical trials.

Submitted by: Greg Z. on Thu, 05/27/2021

I was diagnosed with bulbar ALS in 2013, but had symptoms as early as 2006. Then after a couple of years it was determined I have PLS. My symptoms are very slow to progress, but I can barely speak or walk. I want to be part of the NU9 clinical trial ASAP! Thank you.

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