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Neurological Disorders Overview

Declaration of sponsorship Novartis Pharma AG
Read time: 10 mins
Last updated:11th Oct 2022
Published:25th Aug 2020

Epilepsy is a common, chronic, heterogenous condition with onset commonly in childhood and adolescence and characterised by recurrent and seemingly unprovoked seizures13,14.

Epilepsy can have a devastating impact on quality of life, health and daily living activities15 and classifying, diagnosing and treating epilepsy in adults and children can be difficult.

Treatment options include non-pharmacological, pharmacological and surgical options, and patient-specific factors such as seizure type and genetic factors are key to selecting the best treatment from the wide variety of antiepileptic drugs available 16,17.

AD is a chronic progressive neurodegenerative disorder characterised by cognitive dysfunction, non-cognitive symptoms and difficulties with performing daily living tasks2.

Treatment early in the course of AD helps maintain cognitive and functional performance and delays the emergence of distressing behavioural and psychological symptoms, such as depression, anxiety and apathy3.

Rapid diagnosis is therefore important as is individualised care for this heterogeneous condition. The mainstay of therapy for AD are cholinesterase inhibitors such as rivastigmine4, the partial N-methyl-D-aspartate (NMDA) memantine5 and treatments for secondary symptoms including antidepressants, antianxiety agents and antipsychotics. Drug combinations and different formulations may be useful to maintain treatment adherence and persistence6.

Affecting 8 – 12% of children worldwide, ADHD is the most commonly diagnosed neurodevelopmental disorder7. This heterogeneous condition is characterised by the core symptoms of impulsivity, hyperactivity and inattention8,9 and is more frequently observed in males and individuals with other neurological conditions including epilepsy and autism spectrum disorder (ASD)10.

Although onset of ADHD usually occurs in childhood, it can affect patients throughout their life, and can cause academic underachievement, unemployment, relationship and legal problems, substance abuse, psychiatric illness and higher mortality in adults9–11.

While no curative treatment has been identified, ADHD can be well managed through psychological and pharmacological interventions with stimulants such as methylphenidate being an established treatment12.  Early diagnosis and treatment adherence are particularly important7.

Migraine affects quality of life and a patient’s functional ability during, immediately after, and between migraine episodes. Consequently the condition has a large socioeconomic impact18,19.

Migraine pain starts with ‘abnormal’ activation of the trigeminovascular system (TGVS) which causes release of various neuropeptides at the meninges that can induce neurogenic inflammation including calcitonin gene-related peptide (CGRP)20,21.

Until recently, treatment for migraine prevention utilised drugs developed for other conditions such as antihypertensives, antidepressants, antiepileptics and botulinum toxin type A22,23. However, agents targeting the CGRP pathway have been the recent focus of migraine research, and erenumab was the first human monoclonal antibody injection blocking the activity of CGRP to be approved for migraine prevention24.

MS attacks myelinated axons in the central nervous system, destroying the myelin and the axon to produce eventual physical disability. Cognitive impairment progresses continuously and is associated with brain atrophy and lesion accumulation25.

There are four types of MS based on the frequency of symptoms, time to disease progression and lesion development26 and correct diagnosis aids treatment decisions:

  • Relapsing-remitting MS (RRMS)
  • Secondary progressive MS (SPMS)
  • Primary progressive MS (PPMS)
  • Progressive-relapsing MS (PRMS)

Disease-modifying treatments for MS fall into several categories, interferons (e.g. interferon beta-1b27), sphingosine 1-phosphate (S1P) receptor modulators (e.g. Siponimod28, fingolimod29), monoclonal antibodies (e.g. ocrelizumab30) and various immunomodulators. There are currently more treatments available for relapsing forms of MS but there are several treatments in clinical development for all types of MS.

There are no disease-modifying treatments for the progressive neurodegenerative condition PD and current medical management focuses on controlling the classic motor symptoms of bradykinesia, tremor, rigidity and postural instability31,32.

Dopaminergic pharmacotherapies, such as levodopa, designed to restore depleted dopamine in the substantia nigra pars compacta are the mainstay of PD treatment and need to be administered with agents to prevent endogenous dopamine breakdown.

Around 90% of levodopa is inactivated by catechol-O-methyl transferase (COMT)33 but adjunctive COMT inhibitors such as tolcapone, entacapone and opicapone, prolong the half-life of levodopa and significantly improve its delivery to the brain which helps control motor symptoms32.

SMA is a heterogeneous genetic neuromuscular disease caused by loss of function mutations or deletions in the SMN1 gene, which results in insufficient levels of the survival of motor neuron (SMN) protein causing muscular atrophy and multi-organ disease34.  

An additional gene, SMN2 can produce low levels of functional SMN protein but cannot compensate for the loss of SMN1 present in these patients and the number of copies of SMN2 genes in SMA correlates inversely with age of onset and disease severity35.

A multidisciplinary approach is important for treating patients which include extremely compromised neonates through to infants to adults with minimal symptoms36. Until recently treatment focussed mainly on orthopaedic, pulmonary and nutritional management but excitingly two SMN-targeted treatments, nusinersen (Spinraza) and gene therapy onasemnogene abeparvovec (Zolgensma), have been approved that address the underlying cause of the illness37,38. In addition, a number of small molecules drugs are in development for SMA. These include branaplam39 and risidiplam40 which target SMN2 splicing to increase full length SMN protein.

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