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ABSTRACT
Introduction
Neurometabolic disorders remain challenging to treat, largely due to the limited availability of drugs that can cross the blood–brain barrier (BBB) and effectively target brain impairment. Key reasons for inadequate treatment include a lack of coordinated knowledge, few studies on BBB status in these diseases, and poorly designed therapies.
Areas covered
This paper provides an overview of current research on neurometabolic disorders and therapeutic options, focusing on the treatment of neurological involvement. It highlights the limitations of existing therapies, describes innovative protocols recently developed, and explores new opportunities for therapy design and testing, some of which are already under investigation. The goal is to guide researchers toward innovative and potentially more effective treatments.
Expert opinion
Advancing research on neurometabolic diseases is crucial for designing effective treatment strategies. The field suffers from a lack of collaboration, and a strong collective effort is needed to enhance synergy, increase knowledge, and develop a new therapeutic paradigm for neurometabolic disorders.
Article highlights
The blood–brain barrier (BBB) is a highly selective semipermeable border that separates the circulating blood from the brain’s extracellular fluid in the central nervous system. It plays a crucial role in maintaining a stable environment for the brain and in protecting it from potentially harmful substances.
While essential to protect the brain, the BBB represents a major challenge when it comes to treat conditions that affect the central nervous system, especially rare diseases and neurometabolic diseases, due to the inability of many therapeutic molecules to cross the barrier.
Neurodegenerative diseases are caused by progressive dysfunction and loss of neurons in specific brain regions, associated with alterations in brain connectivity and cognitive decline.
Neurometabolic diseases are inborn errors of metabolism with neurological manifestations. They have in common the alteration of a cellular metabolic pathway, as a starting point, leading to a neurological clinical phenotype.
An efficient and targeted drug delivery to the brain, specifically enzyme delivery for disorders due to deficits of metabolic enzymes, remains a major challenge, as well as an important objective to be achieved when treating this important group of disorders. Both physiological and synthetic delivery systems have been evaluated in the last few years with different success, aiming at transporting these active molecules to the right target within the cell.
Declaration of interest
A Garcia-Cazorla has received honoraria for research support and lectures from PTC Therapeutics, honoraria for lectures from Biomarin, Immedica, and Recordati Rare Diseases Foundation, and is a co-founder of the Hospital Sant Joan de Déu start-up ‘Neuroprotect Life Sciences.’ The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.