Good information always bears repeating and when it comes to ALS and disease modifying therapy, it’s certainly worth circling back for a discussion. For some, this information will be a review of what you already know. For others that are newly diagnosed, I hope this serves as a primer and introduction to these three FDA-approved disease modifying therapies.
Riluzole was the first disease modifying drug to be FDA approved in 1995. Riluzole is an oral medication. It is taken in pill form, by mouth or via a feeding tube, twice daily.
How does it work ? The way in which riluzole works is by inhibiting the release of glutamate. Glutamate is what we call an excitatory neurotransmitter. Neurotransmitters are chemicals that help transmit messages between nerves and other nerves or between nerves and muscles. While glutamate has an important and normal role as an excitatory neurotransmitter, too much excitation is not good for the motor neuron and can lead to cell damage or cell death.
What can it do for you? The original trials suggest that riluzole typically extends tracheostomy-free survival by 2–3 months.
Are there any side effects? Liver enzymes may reach abnormal levels in some patients taking riluzole. We watch this closely so that we can reduce the dosage or stop the medication if this happens. We do this by checking liver function blood tests every month for the first three months that a patient is taking riluzole and then once every three months after that for the duration that one remains on the medication. Some patients may experience some GI discomfort as well.
Radicava (edaravone) is the second medication that was approved for ALS in 2017. It was originally approved as in intravenous infusion but is now available in the oral suspension form known as Radicava ORS. Most patients are on the oral formulation as this prevents any adverse effects that might occur from having a port for intravenous administration. This suspension is taken orally or via a feeding tube in a cyclical fashion where a patient takes the medication for 10 out of 14 days, followed by 14 days completely off of the medication.
How does it work? Radicava works in a different way than riluzole. This medication is a free radical scavenger and it decreases oxidative stress on the motor neurons. A free radical scavenger is a substance, like an antioxidant, that helps protect cells from the damage caused by free radicals. Free radicals are unstable molecules that are made daily during normal cell functioning. Oxidative stress happens when there are too many free radicals in the body and not enough antioxidants to get rid of them. This can lead to damage to the motor neurons.
What can it do for you? Studies show that those patients who take Radicava experience a slower decline (approximately 33%) in their ability to perform their daily activities when compared to placebo.
Are there any side effects? Patients taking Radicava may experience bruising, weakness when walking, and headaches.
Relyvrio (taurursodiol/sodium phenylbutyrate)
Relyvrio is the latest addition to our toolkit, having just been approved by the FDA in the fall of 2022. You may have heard of it as AMX0035. Relyvrio is a combination medication of taurursodiol, which is a bile acid, and sodium phenylbutyrate. It comes packaged in powder form. The powder is mixed with 8oz. of water and can then be taken orally or via a feeding tube. Patients start off by taking one packet a day for 3 weeks and then increase to the full dose of one packet twice a day after that.
How does it work? The endoplasmic reticulum and mitochondria are two small parts of the neurons involved in energy metabolism and storage. The ALS disease process can put stress on these tiny parts of the motor neuron which then accelerates cell damage. Relyvrio slows this damaging process down.
What can it do for me? On average, patients on Relyvrio experienced a decline of 1.24 points per month on their ALSFRS-r scores, which was clinically meaningful and significantly slower than the 1.66 points lost monthly by those on a placebo; in other words, it slowed decline by 25%.
Are there any side effects? Diarrhea can be a side effect of this medication, and this is why we start off slow at half the dose. Some patients will experience mild elevation in blood pressure because of the sodium in the sodium phenylbutyrate component of the medication, which is often easily treated.
I am going to add the medication Nuedexta here as well, even though it is not an FDA approved medication specifically for ALS, but rather for PBA (pseudobulbar affect disorder). Nuedexta, like Relyvrio, is a combination medication that is composed of dextromethorphan and quinidine. It is taken in pill form twice daily.
How does it work? Unknown but likely regulates excitatory neurotransmission.
What can it do for me? Many patients with ALS are taking Nuedexta because PBA is something that can occur in the ALS disease process. PBA often gives symptoms of emotional disturbance such as excessive/inappropriate laughing or crying. That being said, it was also noted that people taking Nuedexta who also had bulbar symptoms, such as difficulty speaking and swallowing, experienced some improvement in those symptoms. Looking at it from this angle then, it may have some disease modifying or changing properties as well as being a great medication to treat PBA.
Are there any side effects? Some people with cardiac rhythm abnormalities cannot take this medication as it can cause abnormalities in the way the heart sends its impulses. This is why we obtain an EKG before starting Nuedexta.
Though I wish we had more FDA approved medications to slow the progression of ALS, the good news is that those we have are all very safe and can all be taken together. There are no interactions between these medications which means that many patients living with ALS can and should be on all three! We don’t have any studies to show how or if these medications might work better or more efficiently when used together but since they work on different “pathways” in the disease process, it is possible that they could. That remains to be seen as we continue to monitor the progression of our patients through time.