Albert Sufianov

Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic platform for central nervous system disorders, including neurodegenerative diseases and lysosomal storage disorders (LSDs). This review examines MSC mechanisms of action—paracrine activity, immunomodulation, antioxidant effects, TFEB-mediated autophagy regulation, and enzymatic cross-correction in LSDs—while critically assessing translational challenges. We provide a comparative analysis of MSC sources, administration routes, dosing regimens, and safety profiles, with emphasis on hemocompatibility and thrombotic risks. The evidence base for MSC efficacy in amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and LSDs is systematically reviewed, highlighting both promising signals and limitations. MSC-derived extracellular vesicles are discussed as a cell-free alternative with improved safety and potential blood–brain barrier interaction. We propose an individualized monitoring framework integrating clinical scales, biomarkers, and neuroimaging. Despite preclinical promise, the field faces major hurdles: product standardization, optimal dosing, and the need for large, randomized controlled trials. The most rational path forward lies in combination strategies—MSCs as adjuncts to gene or enzyme replacement therapy—and engineered platforms for sustained delivery. This review provides a roadmap for translational decision-making and identifies critical gaps that must be addressed before MSC-based therapies can be integrated into routine neurological practice.

Adeno-associated viral (AAV) vectors have established themselves as a promising platform for genetic material delivery in clinical practice, evidenced by regulatory approval of multiple therapeutics. Despite proven therapeutic efficacy, safety concerns remain a critical limitation requiring systematic analysis. This review analyzes clinical data to identify mechanisms of toxicity, clinical risks, and strategies for their minimization in AAV gene therapy. The study examines dose-dependent toxicity, immune responses, and organ-specific burdens associated with systemic and local administration routes. Analysis reveals a clear correlation between systemic delivery efficacy and dose-dependent toxicity, with principal mechanisms including capsid-directed immune responses, hepatic burden, and complement system activation leading to thrombotic microangiopathy. Key determinants of the safety profile include pre-existing neutralizing antibodies, vector dose, serotype selection, and patient baseline conditions. Contemporary strategies for toxicity minimization are evolving from reactive management toward proactive risk mitigation, including prophylactic immunosuppressive regimens, vector engineering to alter tropism or reduce immunogenicity, and rigorous post-infusion monitoring. Integration of improved vector constructs, rational immunosuppressive regimens, and rigorous post-infusion surveillance has the potential to expand the therapeutic window of AAV-based gene therapy, achieving an optimal balance between efficacy and safety for a broader patient population.

Pompe disease (PD) is a neuromuscular autosomal recessive disorder caused by mutation in the GAA gene, which encodes acid α-glucosidase (GAA), an enzyme responsible for hydrolyzing glycogen to glucose. Deficiency of this enzyme leads to pathological accumulation of glycogen in almost all tissues of the body, with the most pronounced effects in cardiac and skeletal muscle, as well as in the central nervous system. Two major clinical forms of PD are recognized: infantile-onset PD, characterized by almost complete absence of GAA activity and severe cardiomyopathy and neurological abnormalities, and late-onset PD, which primarily presents with impairment of respiratory and motor function. Since 2006, enzyme replacement therapy with recombinant GAA has been used to treat PD, improving survival and quality of life. However, this approach has several limitations: the need for lifelong infusions, the risk of immune responses, and the inability of the enzyme to cross the blood–brain barrier, which is particularly critical for infantile-onset PD. Consequently, alternative strategies are being developed, including gene therapy using adeno-associated virus vectors for GAA delivery to target tissues; these approaches are currently in phase I/II clinical trials. Transplantation of genetically modified hematopoietic stem cells also represents a promising therapeutic strategy, offering a single-intervention treatment with long-lasting effects. This review discusses the molecular mechanisms of PD, current and emerging disease models, and therapeutic approaches, which together open prospects for the development of potentially one-time curative treatments, despite persistent challenges such as immunogenicity and the need for long-term efficacy monitoring.

Injuries and diseases of the peripheral nervous system (PNS) often result in irreversible functional deficits. Current therapeutic approaches demonstrate limited efficacy, which has driven the development of regenerative medicine strategies. This review systematizes contemporary gene and cell therapy approaches aimed at PNS repair and regeneration. Key neurotrophic factors (NGF, BDNF, GDNF, VEGF, etc.) and the molecular mechanisms underlying their regenerative effects are discussed. Gene delivery strategies employing viral and plasmid vectors are analyzed, along with the therapeutic application of various cell populations, including Schwann cells, mesenchymal stromal cells, and derivatives of induced pluripotent stem cells. Particular attention is given to combined gene–cell-based approaches, which enable localized and sustained expression of therapeutic molecules. The integration of advances in genetic engineering, cell biology, and tissue engineering is shaping a new treatment paradigm focused on pathogenetic restoration of nerve tissue. These promising strategies pave the way toward achieving complete functional regeneration following PNS injuries.

Currently, the development of adeno-associated virus (AAV)-based gene therapy is a promising method for treating various diseases and is gaining increasing popularity. However, the use of AAV has certain drawbacks and faces limitations such as immune responses and an increased risk of insertional mutagenesis, which have not always been adequately considered in the context of AAV therapy. Moreover, a significant limitation for the application of AAV lies in the challenge of producing it in large quantities. This article discusses the use of AAV in treating various diseases, reviews AAV production approaches, highlights challenges with insufficient viral titers during production, and explores potential solutions at key stages of AAV drug production.

Neutralizing antibodies (nAbs) are an important component of the immune system, which plays a dual role in modern medicine. On the one hand, they significantly limit the effectiveness of gene therapy based on viral vectors, reducing the effectiveness of treatment of diseases such as spinal muscular atrophy, which is especially evident with repeated administration of therapeutic vectors. On the other hand, nAbs is a promising tool for combating viral infections. This review systematizes current data on the mechanisms of nAbs formation against AAV vectors, analyzes the factors influencing their production, and discusses strategies to overcome this limitation, including modification of vectors and the development of methods to suppress the immune response. Special attention is paid to the prospects of using nAbs as therapeutic agents against viral infections. The key problems and possible directions of research development in this area are considered, which is important for improving approaches to the treatment of both rare genetic and infectious diseases.

Eye diseases can significantly affect the quality of life of patients due to decreased visual acuity. Although modern ophthalmological diagnostic methods exist, some diseases of the visual system are asymptomatic in the early stages. Most patients seek advice from an ophthalmologist as a result of rapidly progressive manifestation of symptoms. A number of inherited and acquired eye diseases have only supportive treatment without eliminating the etiologic factor. A promising solution to this problem may be gene therapy, which has proven efficacy and safety shown in a number of clinical studies. By directly altering or replacing defective genes, this therapeutic approach will stop as well as reverse the progression of eye diseases. This review examines the concept of gene therapy and its application in the field of ocular pathologies, emphasizing the most recent scientific advances and their potential impacts on visual function status.

Epilepsy is a brain disorder characterized by a persistent predisposition to epileptic seizures. With various etiologies of epilepsy, a significant proportion of patients develop pharmacoresistance to antiepileptic drugs, which necessitates the search for new therapeutic methods, in particular, using gene therapy. This review discusses the use of adeno-associated viral (AAV) vectors in gene therapy for epilepsy, emphasizing their advantages, such as high efficiency of neuronal tissue transduction and low immunogenicity/cytotoxicity. AAV vectors provide the possibility of personalized therapy due to the diversity of serotypes and genomic constructs, which allows for increasing the specificity and effectiveness of treatment. Promising orientations include the modulation of the expression of neuropeptides, ion channels, transcription, and neurotrophic factors, as well as the use of antisense oligonucleotides to regulate seizure activity, which can reduce the severity of epileptic disorders. This review summarizes the current advances in the use of AAV vectors for the treatment of epilepsy of various etiologies, demonstrating the significant potential of AAV vectors for the development of personalized and more effective approaches to reducing seizure activity and improving patient prognosis.

Epilepsy is a brain disease characterized by a persistent predisposition to epileptic seizures. The current issue is the development of new methods of epilepsy therapy, In particular, using gene therapy methods. Promising areas of research in this field are the modulation of the expression of a number of neuropeptides, ion channels, transcription factors, neurotrophic factors, etc., as well as the use of antisense oligonucleotides. One of the optimal vectors for the delivery of therapeutic transgenes is the adenoassociated virus (AAV), which is most often used in the gene therapy of neurological disorders due to the high transduction ability of neuronal tissues and low immunogenicity/cytotoxicity. In this study, we analyze the existing achievements in the use of AAV vectors in the treatment of epilepsy of various etiologies.

Background The dysmorphogenetic arachnoid cysts’ pathomechanism is most favoured, and about 50% occur as middle cranial fossa cysts (MCFAC). Still being rare, management options are yet evolving. We described the clinico-radiological features, management and early outcomes of participants with MCFAC in our service. Methods This prospective cohort study involved 29 pediatric participants recruited (from electronic health records, using ICD G93.0 D016080 for arachnoid cysts) between 01/01/2023 and 31/06/2023, following informed consent according to the ethical approval. All participants had neuro-imaging confirmed MCFAC. Baseline and follow-up data were retrieved and analyzed using summary (mean, standard deviation) and inferential (ANOVA, t-test) statistics. Results They were averagely aged 6.2 ± 4.48 years and were mostly males (89.7%). 24.1% were asymptomatic. The commonest symptoms (n = 38) were headaches (23.7%), developmental delays (15.8%), eye complaints (15.8%) and cephalomegaly (7.9%). They were predominantly left-sided (89.7%). Galassi (G) 3 lesions were less (24.1%), with G2 and G1 lesions evenly sharing the rest. The average cyst volume was 58.4 ± 80.83cm³; there were significant differences (F = 4.682; p = 0.018) between the average volumes for G1 (14.4 ± 22.42cm³), G2 (61.7 ± 89.92cm³) and G3 (122.5 ± 94.37cm³) lesions. 44.8% of the participants had rigid-endoscopic cysto-cisternotomy (all between the ICA and oculomotor nerve into the interpeduncular cistern, using ventriculostomy forceps); including all G3, 50% of G2 and no G1 (had serial clinico-radiological observation) lesion. The average pre- (117.42cm³) and post-operative (53.48cm³) cyst volumes showed significant (t = − 2.797, p = 0.021) reductions. Conclusion Middle cranial fossa arachnoid cysts occur predominantly amongst males, in middle childhood and left-sided. The treatment-related patient series are largely symptomatic, unlike the largely asymptomatic, screening-related series. Higher Galassi grade lesions presented with progressively, significantly larger cyst volumes and higher likelihoods of surgery. The average post-operative cyst volume at follow-up averagely showed almost 60% reduction from the pre-operative. All participants reported clinical remission.