Targeted Drug Delivery in Immune Diseases

Dear Colleagues,

Autoimmune and neurodevelopmental disorders result from an improper immune response toward a self-antigen. Predominantly, autoimmune and neurodevelopmental diseases have been treated using therapies that suppress systemic immune responses, which can result in significant side effects. Alternatively, immune tolerance induction through antigen-specific treatments can inhibit disease-associated responses without systemic suppression. Previously, immune tolerance has been accomplished via soluble antigen delivery through oral, nasal, or sublingual routes. However, these therapies have shown minimal success in clinical settings.

Multiple sclerosis (MS) is a neurodegenerative condition of the central nervous system (CNS) that presents with varying levels of disability in patients, displaying the significance of timely and effective management of this complication. Though several treatments have been developed to protect nerves, a comprehensive improvement in MS is still considered an essential bottleneck.

Autism spectrum disorder (ASD) is characterized by high heritability and clinical heterogeneity. The main core symptoms are social communication deficits. No medications are approved for treating these symptoms and the medicines used to treat non-specific symptoms have serious side effects. To identify potential drugs for repurposing to treat ASD core symptoms effectively, working groups of international academic, regulatory, and industry representatives have held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a rapidly progressing neurodegenerative disease that leads to muscular atrophy via the degeneration of both upper and lower motor neurons. Mechanistically, ALS has been linked to oxidative stress, protein misfolding, protein homeostasis imbalance, and dysfunction of the serotonergic and dopaminergic system, which are changes that extend beyond the motor cortex. Indeed, the degeneration and dysfunction of the frontal cortex have been established in ALS cases; abnormalities are also evident in the basal ganglia and mid-cingulate cortex.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a complex pathology characterized by inflammation of the joints, devastation of the synovium, pannus formation, and bone and cartilage destruction and is often associated with persistent arthritic pain, swelling, stiffness, and work disability. In conventional RA therapy, poor bioavailability and high and frequent dosing are required because of the short biological half-life. These anti-RA medications, which cannot selectively target the affected zone, may cause severe side effects in extra-articular tissues. Today, nanotechnology has emerged as a promising tool in developing novel drug delivery systems for treating and diagnosing intractable diseases such as RA.

Psoriasis is an autoimmune disease affecting the skin and has a worldwide prevalence. Different immune/non-immune cells, e.g., T cells, macrophages, neutrophils, and keratinocytes, play a decisive role in the pathogenesis of psoriasis. These immune cells interact among themselves by releasing multiple mediators, which eventually cause characteristic psoriatic plaques in the skin. T cells are reported to significantly contribute to psoriatic inflammation by releasing multiple cytokines controlled by various pathways such as tyrosine kinases and transcription factors. This knowledge may be utilized to specifically target a crucial pathway responsible for dermal inflammation, which can alleviate disease symptoms.

Systemic lupus erythematosus (SLE), an autoimmune disease, is characterized by abnormal inflammatory responses due to complex, aberrant humoral and cellular immune responses. The pathogenesis of SLE is mainly unknown; however, data from the literature suggest that the manifestation of this disease results from several environmental, hormonal, and nutritional factors that, in predisposed subjects, contribute to impaired cellular and humoral immune responses.

Prof. Dr. Sheikh Fayaz Ahmad
Prof. Dr. Ahmed Nadeem
Guest Editors

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• autoimmune disorder
• neurodevelopmental disorder
• multiple sclerosis
• autism spectrum disorder
• rheumatoid arthritis