ALS News: Breakthrough Drug Shows Promising Results in Clinical Trials

Introduction

Recent ALS news reveals a groundbreaking personalized drug therapy that has demonstrated remarkable efficacy in slowing ALS progression. In April 2024, a patient received the first-ever antisense oligonucleotide (ASO) treatment targeting CHCHD10 mutations in amyotrophic lateral sclerosis, resulting in a reduction of disease progression by more than half. This development represents a crucial advancement in a field where patients typically survive only about three years after diagnosis.

The landscape of ALS treatment news has undergone substantial evolution over the past decade. Additionally, the hunt for effective ALS drugs in development has yielded six FDA-approved medications. However, this new ALS treatment marks an unprecedented approach through its highly targeted genetic mechanism. Notably, while the average post-diagnosis survival remains approximately three years, about 20% of patients live five years or longer, with 5% exceeding a 20-year life expectancy. The 2025 ALS Drug Development Summit in Boston brought together over 150 stakeholders across various sectors to accelerate therapeutic breakthroughs for ALS and FTD.

This article explores the evolution of ALS treatments, from the early use of Rilutek to the latest personalized antisense oligonucleotide (ASO) therapies that target specific genetic mutations. It delves into the development of the CHCHD10-targeting drug, outlining the science behind its creation and its impact on patient outcomes. The article also reviews the clinical responses observed with this breakthrough therapy. It concludes with an overview of the current research pipeline and emerging directions that are shaping the future of ALS treatment.

ALS Treatment Timeline: From Rilutek to Qalsody

The evolutionary pathway of ALS treatments spans three decades, marked by increasingly targeted approaches that address specific disease mechanisms. Each therapeutic advancement has built upon previous research, offering incremental benefits to patients with this devastating condition.

1995: Rilutek and Glutamate Inhibition

For many years, Riluzole (Rilutek) stood as the sole treatment option for ALS patients. Approved by the FDA in 1995, this benzothiazole drug operates primarily by reducing glutamate excitotoxicity [1]. Its mechanism of action works on several fronts: by blocking sodium channels on presynaptic neurons, Rilutek reduces the excessive release of glutamate, a key contributor to neuronal toxicity in ALS. At the same time, it enhances glutamate reuptake through astrocytic EAAT2 channels, helping to clear excess neurotransmitter from the synaptic cleft. Additionally, it noncompetitively inhibits AMPA and NMDA glutamate receptors, further protecting motor neurons from excitotoxic damage.

The standard dosage remains 50 mg twice daily, as established in early clinical trials. Though initial studies demonstrated modest survival benefits of 2-3 months [2], subsequent real-world analyses suggest potential survival extensions of up to 19 months [3].

2017: Edaravone and Oxidative Stress Reduction

Following a 22-year gap without new treatments, edaravone (Radicava) received FDA approval in 2017 after earlier approvals in Japan and South Korea [4]. Initially used for acute stroke intervention in Japan, this pyrazoline-based compound functions as a free radical scavenger [5].

Edaravone’s approval was based on a randomized phase III trial, which showed a 33% reduction in ALSFRS-R decline over 24 weeks in early-stage patients [5]. Initially administered as an intravenous infusion on a complex schedule (14 days first cycle, then 10 days monthly), an oral suspension formulation (105 mg/day) gained FDA approval in 2022 [1].

2023: Qalsody Targets SOD1 Mutation

April 2023 marked a significant shift toward genetic precision medicine with the FDA’s approval of Qalsody (tofersen) [6]. This antisense oligonucleotide (ASO) targets mutations in the superoxide dismutase 1 (SOD1) gene, affecting approximately 2% of ALS cases—roughly 500 people in the United States [6].

Qalsody received accelerated approval based on its ability to reduce plasma neurofilament light chain (NfL), a biomarker of neurodegeneration [7]. The treatment involves intrathecal administration (spinal injection) with an initial three doses at 14-day intervals, followed by maintenance dosing every 28 days [7].

2024: Personalized ASO for CHCHD10 Mutation

In March 2024, the first ultra-rare ALS patients with CHCHD10 gene mutations began receiving customized ASO treatments [8]. Under the “Silence ALS” initiative, nine patients have received nL-CHCHD-001, designed to reduce levels of the CHCHD10 protein involved in mitochondrial function [8].

This groundbreaking approach exemplifies the shift toward personalized medicine for ALS. Although developing the initial personalized treatment required three years and $1.2 million [6], future applications targeting the same gene are expected to be considerably more expeditious.

Inside the Breakthrough: How the New ALS Drug Was Developed

The development of personalized antisense oligonucleotide (ASO) treatments represents a paradigm shift in ALS therapeutic approaches. Unlike earlier broad-spectrum interventions, these targeted therapies address specific genetic mutations underlying the disease.

Gene Identification and CHCHD10 Mutation

The CHCHD10 gene plays a crucial role in mitochondrial function, particularly in maintaining cristae morphology and mitochondrial remodeling [9]. Mutations in this gene disrupt the mitochondrial contact site and cristae organizing system (MICOS) complex, leading to respiratory chain deficiency and mitochondrial network fragmentation [10]. First identified in 2014, CHCHD10 mutations have since been confirmed in various neurodegenerative phenotypes, including:

Mitochondrial myopathy
Frontotemporal dementia
Late-onset spinal motor neuronopathy
Axonal Charcot-Marie-Tooth neuropathy

In particular, the discovery of heterozygous mutations clustered in exon 2 of CHCHD10 provided a precise target for therapeutic intervention [11]. The p.Gly66Val variant, among others, has been associated with slower ALS progression and extended survival duration—characteristics that helped researchers prioritize this gene for targeted drug development [9].

ASO Design and Preclinical Testing

Antisense oligonucleotides operate by binding to RNA and preventing the production of toxic proteins [12]. For CHCHD10-targeting ASOs, designers created short DNA pieces specifically matched to the mutation’s genetic sequence. The development process involved:

Identification of the optimal genetic sequence to target
Design of ASOs that could silence the mutated gene while preserving regular copies
Testing in patient-derived stem cell models

Researchers optimized their methods to obtain functional motor neurons in merely two weeks, allowing for faster drug screening [13]. These lab-based models demonstrated increased susceptibility to cell death compared to healthy controls, providing a measurable endpoint for testing ASO efficacy [13].

3-Year Development Timeline and $1.2M Cost

From initial design to patient administration, the CHCHD10-targeting ASO required three years of intensive development at a cost of approximately $1.2 million [14]. In contrast to mainstream drug development, which typically requires $1-3 billion and at least 10 years [15], this accelerated timeline reflects the advantages of the rare disease development pathway.

The Silence ALS program, a partnership between Columbia University and n-Lorem Foundation, spearheaded this initiative to develop personalized ASO medicines for individuals with unique ALS mutations [12]. The first patient received treatment in April 2024, with the ASO apparently slowing disease progression by more than 50% [14].

Clinical Trial Highlights and Patient Outcomes

Clinical trial results from the latest generation of ALS therapies demonstrate meaningful improvements in patient outcomes, offering new hope in a field historically characterized by limited treatment options.

Improved Strength and Slower Decline

Data from Tofersen (Qalsody) trials revealed substantial benefits for patients with SOD1 mutations. Based on the most recent assessments, patients demonstrated an estimated 52% slowing of disease progression [16]. Furthermore, muscle strength improved in five of the six evaluated patients, with an average improvement of 11.2% in the total score of handheld dynamometry [16]. Patients also gained an average of 5.13 points in functional independence [16]. In European studies, nine of 17 Italian patients who received tofersen for at least four years either stabilized or showed slight improvement [17]. Likewise, German research documented cases where patients improved by up to nine points on the ALSFRS-R scale [17].

Injection Protocol: Every 3 Months

The personalized CHCHD10-targeting ASO follows a quarterly administration schedule, with treatment delivered through spinal injection directly into cerebrospinal fluid [14]. It contrasts with tofersen’s regimen, which includes three initial loading doses at 14-day intervals followed by monthly maintenance doses [16]. Although both treatments require intrathecal administration, their differing schedules reflect variations in drug pharmacokinetics and the durability of target engagement.

10 Additional Patients Now Receiving the Drug

After the promising results observed in the initial CHCHD10 patient, approximately ten additional individuals are currently receiving treatment based on the same drug formulation [14]. The n-Lorem Foundation covers all costs associated with the therapy [14]. As of 2025, expanded access programs have grown substantially, allowing more patients with rare genetic forms of ALS to receive experimental treatments outside traditional clinical trials.

Limitations: Early Intervention is Critical

Early intervention remains crucial for maximizing the effectiveness of ALS treatment. Studies show that delays in diagnosis—often 9 to 12 months after symptom onset—significantly reduce therapeutic benefit, while early-stage treatment yields far better outcomes. Evidence also suggests that presymptomatic genetic carriers may benefit most from intervention before neurodegeneration begins. To explore this, the ATLAS study is investigating whether administering tofersen to asymptomatic SOD1 mutation carriers can delay or prevent disease onset, marking a shift toward earlier, preventative treatment strategies in ALS. [19].

ALS Research Pipeline and What’s Next

Beyond current treatments, the ALS research pipeline continues to expand with innovative approaches aimed at halting disease progression altogether. These emerging strategies represent potential paradigm shifts in the management of ALS.

Ongoing Trials: Stem Cell and mRNA Therapies

Stem cell therapies have gained momentum as potential treatments for ALS. Currently, 15 active clinical trials examine various stem cell approaches, including mesenchymal stem cells and neural progenitor cells. Moreover, mRNA-based therapies, inspired by COVID-19 vaccine technologies, now target specific genetic mutations underlying ALS. These therapies aim to restore proper protein production rather than merely silencing defective genes.

Biomarker Development: Tau and NfL

Advancements in biomarker research now allow for earlier diagnosis and more precise monitoring of ALS progression. Neurofilament light chain (NfL) levels have become a central focus in clinical trials because they closely reflect the rate of neuronal damage, serving as reliable indicators of treatment response. Similarly, phosphorylated tau (p-tau) levels in cerebrospinal fluid offer more profound insights into neurodegeneration patterns, enabling researchers to distinguish between ALS and other overlapping neurological conditions. These biomarkers facilitate:

Earlier intervention opportunities: Detecting elevated NfL or p-tau levels before significant motor decline enables clinicians to start treatment sooner, potentially slowing disease progression before irreversible neuron loss occurs.
Personalized treatment selection: Biomarker profiles help match patients with the most effective therapies, enabling individualized management based on genetic subtype or disease activity.
Precise measurement of therapeutic responses: Continuous monitoring of biomarker fluctuations provides objective feedback on how well a treatment is working, guiding timely adjustments to optimize patient outcomes.

ALL ALS Initiative and Data Harmonization

The Accelerating Leading-edge Science in ALS (ALL ALS) initiative coordinates research efforts across multiple institutions. This collaborative approach standardizes data collection protocols, enabling cross-study comparisons. Hence, researchers can identify subtle patterns in disease progression that might otherwise remain undetected in smaller, isolated studies.

ALS TDI’s Type-1 PRMT Inhibitor Program

The ALS Therapy Development Institute’s research into protein arginine methyltransferase type-1 (PRMT1) inhibitors represents a promising avenue. Initial studies demonstrate these compounds can reduce neuroinflammation and potentially slow motor neuron degeneration. Subsequently, PRMT1 inhibitors entered preclinical testing with Phase I trials anticipated within the next two years.

Conclusion

Over the past three decades, the landscape of ALS treatment has transformed from broad, modestly effective drugs like Rilutek to highly targeted genetic therapies. Today, patients have access to six FDA-approved medications, each addressing distinct disease mechanisms with varying degrees of success. Among these, personalized antisense oligonucleotide (ASO) therapies represent the most significant leap forward. The CHCHD10-targeting ASO, in particular, exemplifies how precision medicine can reshape the disease course—slowing progression by over 50%, allowing for convenient quarterly dosing, and being developed far more cost-effectively than traditional pharmaceuticals.

Yet, challenges remain. Early intervention is essential for achieving the best outcomes; however, diagnosis often occurs 9 to 12 months after symptom onset, when substantial damage has already happened. Still, research continues to move swiftly, with new strategies—such as stem cell and mRNA-based therapies—aimed at halting disease progression entirely rather than merely slowing it.

At the same time, advances in biomarker development are improving early diagnosis and real-time treatment monitoring, enabling clinicians to personalize care with unprecedented precision. Collaborative efforts, such as the ALL ALS initiative, are further accelerating discovery by standardizing data across institutions.

Other promising avenues include the ALS Therapy Development Institute’s work on PRMT1 inhibitors, which may help reduce neuroinflammation and protect motor neurons, with early-phase trials currently underway.

Although ALS remains a devastating diagnosis, its treatment landscape has never been more hopeful. The rise of genetic precision medicine marks a fundamental shift in how neurodegenerative diseases are understood and managed. What once seemed untreatable is now within reach, as patients with even ultra-rare mutations may soon benefit from therapies tailored uniquely to their genetic profiles.

Key Takeaways

Recent breakthroughs in ALS treatment showcase the power of personalized medicine, offering new hope for patients with this devastating neurodegenerative disease.

A personalized antisense oligonucleotide drug targeting CHCHD10 mutations reduced ALS progression by over 50% in clinical trials.
The new therapy costs $1.2M to develop over 3 years, dramatically cheaper than traditional drug development’s $1-3B price tag.
Early intervention is critical – treatment works best when started within 9-12 months of symptom onset, not after significant progression.
Six FDA-approved ALS medications now exist, evolving from broad treatments like Rilutek to precision genetic therapies like Qalsody.
The research pipeline includes 15 active stem cell trials, mRNA therapies, and biomarker development for earlier diagnosis and monitoring.

This represents a fundamental shift from one-size-fits-all treatments to custom-designed interventions targeting specific genetic mutations. While ALS remains challenging, the move toward precision medicine offers unprecedented hope for patients with rare genetic forms of the disease.

Frequently Asked Questions:

FAQs

Q1. What is the most recent breakthrough in ALS treatment? The most recent breakthrough is a personalized antisense oligonucleotide (ASO) therapy targeting CHCHD10 mutations. This treatment has shown promising results in clinical trials, reducing disease progression by more than 50% in some patients.

Q2. How many FDA-approved medications are currently available for ALS? There are currently six FDA-approved medications for ALS. These range from earlier broad-spectrum treatments, such as Rilutek, to more recent precision genetic therapies, like Qalsody, which targets specific mutations.

Q3. Why is early intervention crucial in ALS treatment? Early intervention is critical because treatment is most effective when started within 9-12 months of symptom onset. Delayed diagnosis and treatment can significantly reduce the therapeutic potential of available medications.

Q4. What new approaches are being explored in ALS research? Researchers are exploring several innovative approaches, including stem cell therapies, mRNA-based treatments, and biomarker development, to facilitate earlier diagnosis and improved treatment monitoring. There are currently 15 active clinical trials examining various stem cell approaches.

Q5. How has the development of personalized ALS treatments impacted costs? Personalized treatments, such as the CHCHD10-targeting ASO, have dramatically reduced development costs compared to traditional pharmaceuticals. This particular therapy cost $1.2 million and took three years to develop, in contrast to the typical $1-3 billion and 10+ years for mainstream drug development.