Treating of focal epilepsy: a patent review

2021 ◽  
Author(s):  
Slobodan M Janković ◽  
Nenad Marković ◽  
Tanja Luković
Keyword(s):  
Gene Therapy ◽  
Anticonvulsant Activity ◽  
Viral Vectors ◽  
Focal Epilepsy ◽  
Specific Gene ◽  
Efficacy And Safety ◽  
Treatment Resistant ◽  
Patent Review ◽  
Current Therapies ◽  
New Compounds

Focal epilepsy is one of the most frequent specific type of epilepsies, with 30% treatment-resistant patients. There are several directions researchers can follow to improve existing treatment of focal epilepsy: synthesis of new compounds with anticonvulsant activity, repurposing drugs approved for other indications, finding drugs targeted to specific genetic and biochemical defects that underlie focal epilepsy syndromes, development of viral vectors for specific gene therapy, creation of devices and methods for suppression of seizures by electrostimulation and development of methods to increase safety of epilepsy surgery. Improvement of efficacy and safety of current therapies is necessary, as well as developing targeted treatment of genetic epilepsy syndromes that will not only suppress seizures, but stop further epileptogenesis.

scholarly journals Efficacy and safety of adeno-associated viral vectors based on serotype 8 and 9 vs. lentiviral vectors for hemophilia B gene therapy

2006 ◽  
Vol 5 (1) ◽  
pp. 16-24 ◽  
Author(s):  
T. VANDENDRIESSCHE ◽  
L. THORREZ ◽  
A. ACOSTA-SANCHEZ ◽  
I. PETRUS ◽  
L. WANG ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Lentiviral Vectors ◽  
Hemophilia B ◽  
Efficacy And Safety

scholarly journals Modulation of Adenovirus Vector Tropism via Incorporation of Polypeptide Ligands into the Fiber Protein

2002 ◽  
Vol 76 (17) ◽  
pp. 8621-8631 ◽  
Author(s):  
Natalya Belousova ◽  
Valentina Krendelchtchikova ◽  
David T. Curiel ◽  
Victor Krasnykh
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Genetically Modify ◽  
Adenovirus Vector ◽  
Short Peptides ◽  
Specific Gene ◽  
Negative Consequences ◽  
Carboxy Terminus ◽  
Fiber Protein ◽  
Potential Ligand

ABSTRACT The efficacy of adenovirus (Ad)-based gene therapy might be significantly improved if viral vectors capable of tissue-specific gene delivery could be developed. Previous attempts to genetically modify the tropism of Ad vectors have been only partially successful, largely due to the limited repertoire of ligands that can be incorporated into the Ad capsid. Early studies identified stringent size limitations imposed by the structure of the Ad fiber protein on ligands incorporated into its carboxy terminus and thus limited the range of potential ligand candidates to short peptides. We have previously identified the HI loop of the fiber knob domain as a preferred site for the incorporation of targeting ligands and hypothesized that the structural properties of this loop would allow for the insertion of a wide variety of ligands, including large polypeptide molecules. In the present study we have tested this hypothesis by deriving a family of Ad vectors whose fibers contain polypeptide inserts of incrementally increasing lengths. By assessing the levels of productivity and infectivity and the receptor specificities of the resultant viruses, we show that polypeptide sequences exceeding by 50% the size of the knob domain can be incorporated into the fiber with only marginal negative consequences on these key properties of the vectors. Our study has also revealed a negative correlation between the size of the ligand used for vector modification and the infectivity and yield of the resultant virus, thereby predicting the limits beyond which further enlargement of the fiber knob would not be compatible with the virion's integrity.

scholarly journals Advances in designing Adeno-associated viral vectors for development of anti-HBV gene therapeutics

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Njabulo Mnyandu ◽  
Shonisani Wendy Limani ◽  
Patrick Arbuthnot ◽  
Mohube Betty Maepa
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Public Health Problem ◽  
Treatment Withdrawal ◽  
Delivery Methods ◽  
Hbv Vaccine ◽  
Treatment Regimens ◽  
Hbv Replication ◽  
Current Therapies

AbstractDespite the five decades having passed since discovery of the hepatitis B virus (HBV), together with development of an effective anti-HBV vaccine, infection with the virus remains a serious public health problem and results in nearly 900,000 annual deaths worldwide. Current therapies do not eliminate the virus and viral replication typically reactivates after treatment withdrawal. Hence, current endeavours are aimed at developing novel therapies to achieve a functional cure. Nucleic acid-based therapeutic approaches are promising, with several candidates showing excellent potencies in preclinical and early stages of clinical development. However, this class of therapeutics is yet to become part of standard anti-HBV treatment regimens. Obstacles delaying development of gene-based therapies include lack of clinically relevant delivery methods and a paucity of good animal models for preclinical characterisation. Recent studies have demonstrated safety and efficiency of Adeno-associated viral vectors (AAVs) in gene therapy. However, AAVs do have flaws and this has prompted research aimed at improving design of novel and artificially synthesised AAVs. Main goals are to improve liver transduction efficiencies and avoiding immune clearance. Application of AAVs to model HBV replication in vivo is also useful for characterising anti-HBV gene therapeutics. This review summarises recent advances in AAV engineering and their contributions to progress with anti-HBV gene therapy development.

Pioneering use of gene therapy for pain

2018 ◽  
Author(s):  
Vadym Biloshytsky ◽  
Roman Cregg
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
Chronic Pain ◽  
Cost Efficiency ◽  
Viral Vectors ◽  
Efficacy And Safety ◽  
Adeno Associated Virus ◽  
Promising Alternative ◽  
Large Molecules ◽  
Simplex Virus

The landmark paper discussed in this chapter is ‘Gene therapy for pain: Results of a Phase I clinical trial’, published by Fink et al. in 2011. In this study, the first of its kind, researchers studied the efficacy and safety of a modified herpes simplex virus (HSV) vector used to deliver PENK, which encodes proenkephalin, which is cleaved into the enkephalin peptides Met-enkephalin and Leu-enkephalin, which induce analgesia by acting on opioid receptors. The development of the HSV vector was based in part on results studies in which adenovirus, adeno-associated virus, or non-viral vectors were used to overexpress genes. Overexpression of a variety of large molecules leads to a reduction in pain-related behaviour in animals. Gene therapy in the treatment of chronic pain seems to offer a promising alternative to systemic or highly invasive therapies. However, additional research is needed to determine the safety, effectiveness, and cost-efficiency of this approach.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

scholarly journals Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xuewen Wu ◽  
Li Zhang ◽  
Yihui Li ◽  
Wenjuan Zhang ◽  
Jianjun Wang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Inner Ear ◽  
Viral Vectors ◽  
Survival Rates ◽  
Semicircular Canals ◽  
Dependent Manner ◽  
Syndrome Type ◽  
Dose Dependent

AbstractMutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1−/− mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner’s membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.

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