disease-modifying therapies

Overview

Disease-modifying therapies (DMTs) are treatments intended to alter the underlying course of a disease rather than only relieve symptoms. In clinical practice, the term is used most prominently in multiple sclerosis (MS), where DMTs are designed to reduce inflammatory disease activity, slow accumulation of disability, and influence long-term outcomes. More broadly, the phrase is also used in neurodegenerative disease research to describe interventions aimed at changing disease progression, including efforts in Alzheimer’s disease (AD) and related disorders.

In MS, DMTs are central to modern management and are commonly discussed in relation to treatment initiation, persistence, switching, and comparative efficacy. In AD research, the term is often applied to candidate agents or multitarget strategies intended to modify pathogenic processes such as Beta amyloid accumulation, Beta-secretase 1 activity, or Histone deacetylase 6-related pathways. These approaches contrast with purely symptomatic therapies such as the NMDA receptor antagonist memantine, which is used to manage symptoms rather than directly alter disease biology.

Focus of Latest Publications

Recent publications have examined disease-modifying therapies primarily in the context of MS, with additional use of the term in AD drug-development research.

In relapsing-remitting MS, one study compared use of DMTs between patients with late-onset MS and adult-onset MS. The reported concern was that late-onset disease may lead to underexposure to DMTs relative to adult-onset disease. This indicates that age at onset may influence treatment patterns, potentially affecting access to or uptake of disease-modifying treatment in routine care.

Another MS study evaluated trajectories of processing speed across different DMTs. Using the Symbol Digit Modalities Test as a measure of cognitive performance, the investigators aimed to determine whether therapies of varying efficacy were associated with long-term cognitive trajectories. This reflects an emerging research focus on whether DMTs may influence not only relapse and disability outcomes but also cognition, particularly processing speed, over time.

A related publication on cognition in MS in the modern diagnostic and treatment era noted that a speed-centric model of cognitive impairment was established before DMTs were available and remains influential despite changes in contemporary clinical practice. This context underscores how the introduction of DMTs has altered the clinical landscape, even as older conceptual models of MS cognition continue to shape interpretation of cognitive findings.

Treatment persistence and switching were also examined in people with MS treated with cladribine tablets in Southeast European MS centers. That study assessed treatment completion rates, persistence, administration of a third course of cladribine tablets, and subsequent transitions to other DMTs. The findings were framed around real-world treatment continuation and sequencing, highlighting how DMT use extends beyond initial prescription to long-term management decisions.

In pediatric-onset MS, DMTs were discussed as potentially mitigating cognitive challenges by slowing disease progression and promoting production of neurotrophic factors. The publication emphasized that evidence remains limited, especially in children, but it supports the idea that disease modification may have relevance for cognitive outcomes in younger patients as well.

Outside MS, the term appeared in AD-focused medicinal chemistry research. One study on 1,5-diarylpyrazole-based multitarget-directed ligands described a compound, 11e, as a potent dual COX-2/HDAC6 inhibitor and a promising multitarget scaffold for developing disease-modifying therapies for AD and related neurodegenerative disorders. This places DMTs in the context of mechanism-based drug discovery, where inhibition of Prostaglandin-endoperoxide synthase 2 (COX-2) and Histone deacetylase 6 is explored as part of a broader strategy to influence disease biology.

A separate perspective on BACE 1 inhibitors similarly highlighted the challenge of developing effective disease-modifying therapies for AD. In this setting, Beta-secretase 1 and Beta amyloid are central mechanistic targets, reflecting the longstanding goal of intervening in amyloid-related pathology to achieve disease modification rather than symptomatic benefit alone.

Key Publications

Jun Icariin promotes lysosomal degradation of amyloid-β precursor protein via enhanced endosome-lysosome trafficking to reduce amyloid-β accumulation and improve cognitive function in Alzheimer's disease models. (Brain research bulletin, 2026, PMID 42055146): "...addressing the urgent need for disease-modifying therapies for this devastating neurodegenerative disorder."
May Trajectories of processing speed in multiple sclerosis across disease-modifying therapies. (Journal of neurology, 2026, PMID 42162514): "We aimed to investigate how disease-modifying therapies (DMTs) of varying efficacy are associated with long-term cognitive trajectories in MS, as measured by the Symbol Digit Modalities Test (SDMT)."
May Differences in Use of Disease-Modifying Therapies Between Patients With Late-Onset and Adult-Onset Relapsing-Remitting Multiple Sclerosis. (Neurology, 2026, PMID 42085644): "potentially leading to underexposure to disease-modifying therapies (DMTs) compared with adult-onset multiple sclerosis (AOMS)."
May Cognition in multiple sclerosis within the modern diagnostic and treatment era. (Brain : a journal of neurology, 2026, PMID 41293835): "This speed-centric model was established over three decades ago before disease-modifying therapies were available, and contrasts with our current clinical experience, but nonetheless remains dominant and unquestioned."
May Design and development of 1,5-diarylpyrazole-based multitarget-directed ligands as dual COX-2/HDAC6 inhibitors for Alzheimer's disease therapy: Molecular dynamics and experimental insights. (European journal of medicinal chemistry, 2026, PMID 41785827): "These findings establish 11e as a potent dual COX-2/HDAC6 inhibitor and a promising multitarget scaffold for developing disease-modifying therapies for AD and related neurodegenerative disorders."
May Effects of disease modifying therapy on cognitive proficiency in pediatric-onset multiple sclerosis (POMS). (Multiple sclerosis and related disorders, 2026, PMID 41793805): "Disease-modifying therapies (DMTs) may mitigate well-documented cognitive challenges in pediatric-onset multiple sclerosis (POMS) by slowing disease progression and promoting production of neurotrophic factors, though studies are limited, especially in children."
May Long-term outcomes of cladribine tablets in multiple sclerosis: Treatment completion, persistence, and subsequent therapy transitions in Southeast Europe. (Multiple sclerosis and related disorders, 2026, PMID 41886879): "This study aimed to assess treatment completion rates, persistence, administration of a third course of cladribine tablets, and switching to other disease-modifying therapies (DMTs) in people with multiple sclerosis (pwMS) treated with cladribine tablets in Southeast European MS centers."
Apr Developments on BACE 1 Inhibitors as Anti-Alzheimer Agents: A Perspective on Medicinal Chemistry-Based Advances. (Archiv der Pharmazie, 2026, PMID 41838033): "...highlighting both their therapeutic potential and the challenges that remain in developing effective disease-modifying therapies for AD treatment."