Excitement Building for New Agents in ALS

August 21, 2018

Several clinical trials are examining the role of stem cells, inflammation, and other pathways in ALS.

Mary Sedarous, MD

The number of promising therapies in exploration for amyotrophic lateral sclerosis (ALS) has expanded, as progressively more is learned about the underlying pathology of the disease. Moreover, improvements in manufacturing techniques for cellular therapies has also strengthened the current ALS pipeline.

Research is now illuminating the role of stem cells, inflammation, and other pathways in ALS. Although the mechanism of action is not yet fully understood, the benefits of this research was realized in May 2017, when the FDA approved edaravone (Radicava). This treatment, which is geared toward oxidative stress, was the first drug approved to treat ALS in over 20 years.

To gain further insight into the therapies in development for ALS, NeurologyLive interviewed Mary Sedarous, MD, medical director of the Hackensack Meridian Health ALS Center.

NeurologyLive: What are some of the big trials on your radar?

Sedarous: There are a number of clinical trials looking at the role of neuroinflammation in ALS and hence a number of trials are designed to address this. This includes the NP001, masitinib, and tocilizumab (Actemra) trials as well as NurOwn trials. There are also clinical trials specifically targeting the familial forms of ALS with gene silencing. Yet another group of clinical trials are looking at ways of stopping cells death, such as with AMX0035.

In terms of the NurOwn trial, what are your thoughts on stem cell treatments?

I am optimistic about it. My patients always ask about stem cell clinical trials. I think this is because most people think that the theory behind stem cell trials is that you are creating new motor neurons to replace the ones that are dying. That is not necessarily true. It’s not so much that these cells become motor neurons. Instead these stem cells support the motor neurons that are already there, to halt them from dying back or at best allow them to regenerate. There’s a lot of technical challenges in stem cell research including mechanism of delivery.

Edaravone is one of the first therapies approved in decades. What has your experience been like using it?

The biggest challenge with edaravone was getting it approved by insurance companies. The second challenge was administering the drug, where in a lot of instances an infusion port had to be placed. Putting a port, as such, is a procedure that has its own risks, both immediate and long term. Vascular access carries an inherit risk for infection over time. For those patients who can not get the drug infused at home, they have to travel to an infusion center to get their treatment every cycle. Eventually they get very tired, even if they did it for the first 1, 2, 3, or 6 months. As their disease continues, it becomes more challenging.

The biggest challenges with the drug were nothing related to the drug itself: it was first getting it approved by insurance companies and next administering it. I have had patients that continued to decline quickly on edaravone and in some instances I had to discontinue the drug after careful consideration of risks and benefits with the patients.

We are still waiting for the full phase IV trial that we were promised to have. It’s important because it was never really tested in the United States.

For other drugs that are being tested, like the NurOwn stem cell therapy, what would you want to see in those clinical trial results?

One of the challenges in ALS that we do not have a biomarker for the disease that can be monitored. That is another area of research right now in ALS that I believe is very important. I am hoping that eventually we will be able to develop better biomarkers to monitor disease activity and better measure drug efficacy.

Is there anything you’re working on that you want to highlight?

We did start our very first clinical trial for ALS at Jersey Shore Medical Center. We recently got approval to participate in the Acthar gel clinical trial. ACTH is a molecule that triggers the production of endogenous steroids and thereby decreases inflammation. Back to the idea of neuroinflammation in ALS, the hope is that by decreasing inflammation we may be able to slow disease progression. This clinical trial is also opening sites in Canada.

There’s already been patients recruited for the clinical trial for a number of months now, and we just came on board and we’re hoping to be recruiting our patients soon for this clinical trial. We’re very excited to be able to provide research locally in New Jersey, as patients have long been traveling to participate in research outside the state.