What is the best drug for ALS? A guide to treatment options

Every year, approximately 5,000 people in the U.S. receive a diagnosis of Amyotrophic Lateral Sclerosis (ALS), a progressive and fatal neurodegenerative disease. When faced with this news, many want to know, 'What is the best drug for ALS?' The answer is not a single drug, but a personalized treatment plan combining multiple medications and supportive therapies.

Quick Summary

No single drug is best for all ALS patients. Various treatments, including Riluzole, Edaravone, and Tofersen, can slow progression and manage symptoms, with the optimal choice depending on individual factors and disease characteristics.

Key Points

• No Single Best Drug: The optimal ALS medication depends on the individual's specific condition, disease stage, and genetic factors.

• Riluzole: Modestly extends survival by reducing glutamate-related nerve damage and is available in tablet, liquid, and oral film forms to assist with swallowing difficulties.

• Edaravone: Slows functional decline in certain early-stage patients by targeting oxidative stress and is available via IV or oral suspension.

• Tofersen (Qalsody): A genetically targeted therapy specifically for ALS patients with a SOD1 gene mutation, administered via spinal injection.

• Symptomatic Management: Other medications, such as Nuedexta for pseudobulbar affect, are used to manage a variety of symptoms.

• Multidisciplinary Care: A comprehensive team approach involving physical therapists, respiratory therapists, and other specialists is crucial for managing symptoms and improving quality of life.

The Search for the 'Best' ALS Drug: A Personalized Approach

There is no one-size-fits-all answer to the question of what is the best drug for ALS. Instead, treatment for Amyotrophic Lateral Sclerosis (ALS) is a multifaceted strategy tailored to each patient's unique needs. The goal of pharmacotherapy in ALS is not to cure the disease, but to slow its progression, manage debilitating symptoms, and improve overall quality of life. The most effective approach typically involves a combination of FDA-approved medications and comprehensive supportive care from a multidisciplinary team. The specific drug or combination of drugs recommended will depend on the patient's stage of disease, rate of progression, specific symptoms, and in some cases, genetic profile.

Riluzole (Rilutek, Tiglutik, Exservan): The Foundational Treatment

Mechanism of Action: Riluzole was the first drug approved by the FDA for ALS, back in 1995. Its primary mechanism is believed to be the inhibition of glutamate release, a neurotransmitter that is toxic to motor neurons in excess amounts. By reducing the activity of this chemical messenger, Riluzole can help protect nerve cells from further damage and modestly slow the progression of the disease.

Formulations: As swallowing difficulties (dysphagia) are a common symptom of ALS, Riluzole is available in several forms to aid administration.

• Rilutek: The original oral tablet form.
• Tiglutik: A thickened liquid suspension, easier for patients with swallowing issues. It can also be administered via a feeding tube (PEG-tube).
• Exservan: An oral film that dissolves on the tongue, which is particularly beneficial for patients with more severe dysphagia.

Efficacy: Clinical trials have shown that Riluzole can extend survival by several months and delay the need for mechanical ventilation in some patients.

Edaravone (Radicava): The Antioxidant Therapy

Mechanism of Action: Edaravone, approved by the FDA in 2017, is thought to be a free radical scavenger that combats oxidative stress. Oxidative stress is believed to contribute to the damage and death of motor neurons in ALS, and Edaravone's antioxidant properties may help preserve nerve cells.

Administration: Edaravone is administered in a specific, cyclical manner:

• Intravenous (IV) Infusion: Initially delivered as a daily 60-minute IV infusion for 14 days, followed by a 14-day break. Subsequent cycles involve 10 infusions over a 14-day period, also followed by a 14-day break.
• Oral Suspension (Radicava ORS): An oral formulation was approved in 2022, offering a more convenient option for self-administration at home.

Efficacy: A six-month trial showed that Edaravone could slow the decline in physical function for some patients, particularly those in the early stages of the disease.

Tofersen (Qalsody): A Genetically Targeted Treatment

Mechanism of Action: Qalsody is a groundbreaking therapy, approved in 2023, that specifically targets the superoxide dismutase 1 (SOD1) gene mutation. SOD1 mutations lead to the production of toxic proteins that cause nerve cell death. Tofersen works by blocking the production of these abnormal proteins, directly addressing the underlying genetic cause in a small subset of ALS patients.

Administration: Unlike other ALS drugs, Tofersen is delivered via an intrathecal injection (spinal injection) by a healthcare professional.

Efficacy: Tofersen's approval was based on its ability to reduce a biomarker of nerve injury called neurofilament light chain (NfL). Ongoing confirmatory studies are assessing its clinical benefits. This therapy is only relevant for the approximately 2% of ALS patients with the SOD1 gene mutation.

Comparison of Key ALS Medications

Feature	Riluzole (Rilutek, etc.)	Edaravone (Radicava)	Tofersen (Qalsody)
Mechanism	Inhibits glutamate release to protect motor neurons.	Scavenges free radicals to combat oxidative stress.	Antisense oligonucleotide targeting the mutated SOD1 gene.
Target Population	General ALS population.	General ALS population, particularly effective in early-stage patients.	Exclusively for ALS patients with a confirmed SOD1 gene mutation.
Administration	Oral tablet, liquid suspension (Tiglutik), or oral film (Exservan).	Intravenous infusion or oral suspension (Radicava ORS).	Intrathecal (spinal) injection.
Dosing Schedule	Twice daily.	Cyclical (e.g., 14 days on, 14 days off; 10 days on, 14 days off).	Monthly, following initial loading doses.
Primary Benefit	Modestly extends survival time and delays tracheostomy.	Slows the rate of functional decline.	Reduces biomarker (NfL) levels; clinical benefit is being studied.

Symptomatic Treatments and Multidisciplinary Care

Medications that modify the disease's progression are just one part of the treatment equation. Managing symptoms is equally vital for a patient's comfort and well-being. A neurologist and a multidisciplinary care team will often prescribe additional medications and therapies to address specific issues, including:

• Pseudobulbar Affect (PBA): Characterized by involuntary and disproportionate laughing or crying, PBA can be managed with Nuedexta, a combination of dextromethorphan and quinidine.
• Muscle Cramps and Spasticity: Muscle relaxants like baclofen or mexiletine can help alleviate painful cramps and stiffness.
• Excessive Saliva (Sialorrhea): Medications with anticholinergic effects, such as glycopyrrolate or amitriptyline, can reduce saliva production.
• Pain: Over-the-counter pain relievers or stronger medications may be used for musculoskeletal pain.
• Depression and Anxiety: Antidepressants or other therapies can help manage the emotional toll of an ALS diagnosis.

Beyond medication, a comprehensive care team is essential for a holistic treatment approach.

Physical and Occupational Therapy: Helps maintain muscle strength, flexibility, and mobility for as long as possible.

Speech and Swallowing Therapy: Assists with communication and nutritional challenges.

Respiratory Therapy: Aids in managing breathing issues and the use of assistive devices like ventilators.

Nutrition Support: Provides guidance on maintaining adequate nutrition as swallowing becomes difficult.

Assistive Devices: A wide range of devices, from braces and wheelchairs to communication technology, help maintain independence and quality of life.

Conclusion: Personalization is Key

Ultimately, there is no single "best" drug for ALS. The most effective treatment plan involves a personalized combination of disease-modifying medications like Riluzole, Edaravone, and potentially Tofersen (for SOD1-ALS), along with targeted therapies for symptom management. A multidisciplinary team of healthcare professionals is critical for optimizing a patient's care and maximizing their quality of life. As research continues to advance, new therapies like the experimental NurOwn cell therapy show potential, offering new hope for the future. Anyone with an ALS diagnosis should consult with their neurologist and care team to develop a comprehensive plan that addresses their unique situation.

For more information on the latest ALS research and treatment options, please visit the ALS Association website.

Frequently Asked Questions

Are there any drugs that can cure ALS?

No, currently there are no medications that can cure ALS. Existing drugs are designed to slow the progression of the disease and help manage symptoms.

Is Riluzole the only medication for ALS?

No. While Riluzole was the first drug approved for ALS, others like Edaravone and Tofersen (for SOD1-ALS) have since been approved and are part of the therapeutic options available.

How does Edaravone work for ALS?

Edaravone works by acting as a free radical scavenger, which helps to mitigate the oxidative stress believed to contribute to the death of motor neurons in ALS.

Who can use Tofersen?

Tofersen is a genetically targeted therapy only for adults with ALS who have a confirmed superoxide dismutase 1 (SOD1) gene mutation.

Can I take more than one ALS medication at the same time?

Yes, it is common for patients to be on multiple medications. Some clinicians prescribe both Riluzole and Edaravone to target different pathways of the disease, and symptomatic treatments may also be added.

How are swallowing problems addressed with ALS medication?

For patients with dysphagia, or difficulty swallowing, Riluzole is available in a liquid suspension (Tiglutik) and an oral film (Exservan) that dissolves on the tongue.

Is there hope for new ALS treatments in the future?

Yes, research is ongoing, with several promising clinical trials exploring novel therapies like stem cell treatments and gene silencing techniques. This continuous investigation offers hope for future advancements.