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Precision medicine beyond oncology – Precision Neurology

13 Mar 2024

Advances in precision medicine (PM), initially established within oncology, are now garnering increasing attention across various medical specialties. Neurological diseases, characterized by significant genetic and pathophysiological diversity, stand to particularly benefit from the application of PM in both diagnosis and therapy.

Insights gained from genetic studies have served as crucial entry points, illuminating key biological and pathophysiological processes underlying various subtypes of complex neurological diseases. Indeed, over the past five years (2019-2023), genetically informed diagnostic and therapeutic decision making has been approved for various conditions including Duchenne muscular dystrophy, Fabry disease, amyotrophic lateral sclerosis (with or without SOD1 mutation), Rett syndrome, Friedrich’s ataxia, polyneuropathy of hereditary transthyretin-mediated amyloidosis, seizures in cyclin-dependent kinase-like 5 deficiency disorder, Alzheimer's disease (AD) and more.

Alzheimer's disease stands out as one of the most advanced models for precision medicine in neurology, driving advancements in diagnostic and drug development. Genetic variants associated with genes such as APP, PSEN1, PSEN2, and APOE play a pivotal role in assessing susceptibility to AD. Specifically, the genetic status of the ApoE ε4 allele, including homozygous, heterozygous, and noncarriers, serves as a differential diagnostic biomarker to classify Alzheimer's patients and guide the utilization of FDA-approved therapies such as Aduhelm and Leqembi. Additionally, a multi-dimensional biomarker-based classification system known as the “Amyloid-β/Tau/novel candidate biomarkers from additional mechanisms/Neurodegeneration [ATX(N)] system” has been conceptualized to facilitate the further development of the pathway-based, stage-oriented precision medicine therapeutic strategies in AD.

While the PM strategy that has driven recent successes in oncology can offer valuable insights, its application and adaptation in neurology may require the development of specific tactics. Distinct challenges have been identified for the clinical implementation of PM in the neurology field, necessitating tailored approaches to overcome them.

1. Access to brain tissue biopsy is often limited, prompting a demand for liquid biopsy-based biomarker tests to assess one’s neurological conditions. However, the clinical effectiveness and lab capabilities for performing these blood-based tests are still in the developmental stages.

Due to the physical constraints of accessing brain tissue samples, neurological biomarker testing primarily relies on various bodily fluids such as cerebrospinal fluid (CSF), blood (plasma, serum), and more recently, saliva and urine. Among these options, non-invasive blood-based biomarker testing has gained significant interest among healthcare professionals. This approach allows for temporal biomarker analysis, offering insights into the dynamic and progressive temporal profiles of individuals' neurological conditions.

In the Alzheimer's space, plasma Aβ42/Aβ40 tests were among the first blood-based assays to be introduced in clinical settings. Among various emerging blood-based biomarkers for assessing brain amyloid status, plasma p-tau 217 has been identified as a reliable indicator of amyloid pathology, comparable to levels detected in CSF. It outperforms other plasma Alzheimer's biomarkers, including p-tau 181, p-tau 231, Aβ42/40, GFAP, and NfL. Moreover, these blood-based biomarker tests can be conducted inexpensively and at scale, making them suitable for potential expanded use in asymptomatic populations. At the Alzheimer's Association International Conference 2023, a proposal of the inclusion of blood-based markers in clinical guidelines for Alzheimer's testing was brought up by a working group convened by the Alzheimer's Association and the US National Institutes of Health's National Institute on Aging (NIA).

Despite these promising advancements from technological, socioeconomic, and policy perspectives, the incorporation of blood-based biomarker testing into routine clinical practice in neurology is still under development.

2. The adoption of a new biomarker test is influenced by market dynamics and requires significant field force from diagnostics and/or pharmaceutical companies.

Precision medicine in neurology aims to deliver personalized therapies targeting specific molecular pathways underlying patient's neurological conditions. For instance, treatments for Parkinson's disease may focus on neurotransmitter systems or gene therapies to restore dopamine levels, while epilepsy management could involve targeted approaches based on genetic mutations or seizure types. As the number of approved biomarker-informed diagnostics and therapeutics in neurology increases, diagnostic firms are striving to meet the growing testing demand.

However, the adoption of biomarker testing in the PM realm can be influenced by various factors and may take years to reach a desirable testing rate of 80%. Clinical implementation of guideline-recommended functional imaging (fMRI) and PET-based molecular brain mapping of amyloid and tau remains limited, especially for late-onset AD, partly due to the cost and complexity of these techniques. Limited access to samples from patients with confirmed amyloid pathology by PET imaging is also a barrier for new labs adopting tests requiring further verification. Market dynamics related to regulations, guidelines, accreditation requirements, and the testing commission model can also affect biomarker test adoption.

Practical experiences gained from implementing PM in oncology highlight that inefficiencies stemming from inadequate market development planning for biomarker tests could prevent 50% of patients from receiving appropriate testing for biomarker-guided treatment. Therefore, implementing a well-planned biomarker testing market development strategy in advance can ensure accessibility to upcoming PM therapies in neurology.

3. Seamless cross-functional communications are crucial for the successful adaptation of the ATX(N) system, a multi-dimensional biomarker-based classification system. This communication is essential to facilitate the further development of pathway-based, stage-oriented PM therapeutic strategies in neurology.

In neurological diseases, the multi-dimensional biomarker-based ATX(N) classification system relies on test results gathered from diverse platforms. These platforms may be situated across different institutions or departments within the same institution. The tests encompass a range of modalities, including genetic analysis, neuro-imaging studies, transcriptional assays, protein profiling assessment, behavioral data from digital health devices, social interactional metrics, sleep pattern analyses, as well as personal disease history and phenotypical data extracted from electronic health records (EHRs). Considering this multimodal biomarker variables of PM in neurology, cross-disciplinary collaboration is essential to establish a systematic integration of the current partially fragmented scientific, diagnostic, and medical professionals within healthcare providers.

4. Equitable access to diagnostic testing ensures the success of PM in neurology

The PM-oriented approach requires characterization of individuals within the broader context of population-related factors such as sex, ethnicity, geographic location, and socioeconomic status. These factors have been demonstrated to influence access to diagnostic testing and can contribute to inequities in healthcare access and outcomes.

In Alzheimer's disease (AD), research has extensively investigated and revealed a higher vulnerability to AD among menopausal women compared to age-matched men. This finding underscores the importance of considering sex as a critical factor rather than merely treating it as a covariate. Therefore, it is crucial to ensure equitable access to diagnostic testing, especially accessing multi-biomarker testing models, for implementing PM in neurology. Such inclusive approaches can help address the unique needs and vulnerabilities of different demographic groups, ultimately improving healthcare outcomes for all individuals affected by neurological conditions like AD.

In summary, precision medicine in neurology shows great promise in improving diagnostic accuracy, treatment effectiveness, and patient outcomes across a range of neurological disorders. To fully realize its potential in clinical practice, ongoing and customized efforts in navigating and resolving challenges are crucial.

Diaceutics, powered by DXRX®, the diagnostic commercialization platform, offers end-to-end services to pharmaceutical and biotech companies looking to implement precision medicine in neurology. Through DXRX, real-world, real-time diagnostic and prescription data can be leveraged to identify potential pitfalls and ensure awareness, adoption, accessibility, availability, and accuracy related to biomarker-oriented diagnostics and therapies in neurology. This comprehensive approach can help streamline the implementation of PM in neurology and improve patient outcomes by ensuring the right diagnostic tests and therapies are available and accessible when needed.

Register for DXRX today to gain access to real-world data, unlock valuable PM insights, and pave the way for improved patient outcomes by clicking here.

Author: Ying Liu, Director, Domain Expert, Scientific & Advisory Services


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  2. https://www.fda.gov/drugs/development-approval-process-drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products
  3. https://pubmed.ncbi.nlm.nih.gov/32565066/
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  6. https://pubmed.ncbi.nlm.nih.gov/36315914/
  7. https://www.360dx.com/diagnostics/alzheimers-biomarker-research-pushing-plasma-p-tau-217-fore

Precision medicine beyond oncology – Precision Neurology

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