Gaining a Greater Understanding of the Global Burden of Neurologic Disorders

Bruce Leuchter, MD

In 2016, a report ranked neurological disorders as the leading cause of disability-adjusted life years (DALYs) and the second-leading cause of death. At the time, the largest contributors to DALYs were stroke, migraine, and Alzheimer disease (AD) and other dementias. Even with the high burden observed, the analysis did not include neurodevelopmental disorders, as defined by the International Classification of Diseases-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage.

More recently, a published analysis in The Lancet Neurology estimated nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. The study, led by the GBD 2021 Nervous System Disorders Collaborators, showed that these conditions were collectively ranked as the leading group of DALYs in 2021 (443 million, 95% UI, 378-521), affecting 3.40 billion (3.20-3.62) individuals (43.1%; 95% UI, 40.5-45.9 of the global population). Age-standardized rates of deaths per 100,000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardized rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4).

In order, the 10 conditions with the highest age-standardized DALYs in 2021 were stroke, neonatal encephalopathy, migraine, AD and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications because of preterm birth, autism spectrum disorder, and nervous system cancer. Overall, the study provided the latest evidence to guide ongoing advocacy and awareness efforts. As the leading cause of DALYs, affecting more than 40% of the global population, investigators concluded that nervous system health loss should be a public health priority.

Following these data, Bruce Leuchter, MD, a neuropsychiatrist and chief executive officer of Neurvati Neurosciences, provided commentary on the global burden of neurological disease and what the results show. Leuchter gave thoughts on the biggest takeaways from the data, some of the main factors as to why neurologic disorders are among the biggest global health threat, and ways in which to evolve drug development and implement policy changes that will ultimately improve the lives of those living with these disorders.

NeurologyLive^®: For clinicians (and neurologists specifically), what are the greatest takeaways from the research?

Bruce Leuchter, MD: I was a practicing neuropsychiatrist for more than 10 years and saw people living with a range of neurological and psychiatric diseases, including epilepsy, schizophrenia, depression, and neurodegenerative diseases. This latest research in Lancet Neurology reaffirms the significant burden that these diseases present to patients and families and the need for continued investment in research and development of new therapies that can potentially address their root causes and make a meaningful difference in patients’ lives. Many clinicians including neurologists can play an important role in advancing potentially effective treatments by supporting clinical trials of new innovative drugs and encouraging their patients who might be eligible and benefit to seek additional information about ongoing clinical research.

What are some of the main factors as to why neurologic disorders may be the biggest global health threat?

Neurological disorders include congenital and neurodevelopmental disorders, neurodegenerative diseases, rare diseases, epilepsy, migraine and stroke, among many others. These disorders are often heterogeneous, and symptoms can vary widely in severity and frequency. As a result, it can be challenging to give accurate diagnoses as they are often made based on observation of patients’ physical symptoms rather than genetic testing or established biomarker profiles. Without a precise diagnosis, patients may not receive proper disease management or treatment for several months or even years, allowing their diseases to progress. A large proportion of neurological disorders also present significant disease burden due to premature death and long-lasting disability.

In addition, there are currently no available treatments for many neurological disorders. While many researchers are working to develop new therapies with the potential to improve the health and quality of care for millions of patients, several unique challenges in targeting neurological disorders often prevent these therapies from advancing rapidly or derail them entirely. For example, clinical research in neurological indications can be highly complex and take many years to complete, which can drain financial resources. Clinical trial endpoints are often rater-based outcomes that are prone to high degrees of variability and interpretation, which can make it difficult to produce statistically significant and clinically meaningful data. In cases where treatment is available, patient access to these treatments can be limited due to lack of specialized resources, services and expertise, especially in low-income countries.

From a policy and funding perspective, how can we help this field? What needs to be done?

The significant capital requirements to support neurological drug development coupled with challenges such as extended development timelines, patient heterogeneity, and trial design complexities can result in limited investor interest. It is essential that stakeholders in the life sciences industry including drug developers, investors and policymakers develop and support innovative business models that are positioned to address these challenges in order to bring more therapies for neurological disorders to patients.

One emerging option is a private equity model for neurotherapeutics referred to as “identify-evaluate-invest-develop” that is being embraced by development companies including Neurvati Neurosciences and several private equity and venture capital firms. This model targets drugs later in the development lifecycle when there is sufficient clinical data indicating a high probability of success, whereas the classic venture-backed model often used to support neuroscience research targets early-stage technologies or drugs with limited clinical data. One important advantage with the identify-evaluate-invest-develop model is that it can generate interest in a drug that has failed in a prior clinical trial but where a review of available data provides new insights indicating that it may not be a failed drug. In many cases, a comprehensive data review shows clear signs of biological activity and a drug’s potential for development in the same or a different neurological indication based on its mechanism of action.

Are there ways in which we can be more efficient with costs and effective with finding new treatment options?

Under the identify-evaluate-invest-develop business model, firms position industry veterans as entrepreneurial partners who can leverage their expertise, insights and contacts to assess and vet promising drugs in neuroscience indications. Then, they bring together the resources – financial and operational – necessary to advance them through late-stage development and potentially regulatory review as efficiently as possible. This model is positioned to streamline the drug development and investment process and improve operating efficiency. This model can help identify cases where a promising drug is stalled for reasons that are surmountable and work with potentially hundreds of development-stage neurotherapeutics that are currently paused or deprioritized due to lack of R&D budget or are no longer in scope strategically.

REFERENCE
1. GBD 2021 Nervous System Disorders Collaborators. Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024;23(4):344-381. doi:10.1016/S1474-4422(24)00038-3.