scholarly journals A demonstration of cone function plasticity after gene therapy in achromatopsia

2020 ◽  
Author(s):  
Mahtab Farahbakhsh ◽  
Elaine J. Anderson ◽  
Andy Rider ◽  
John A. Greenwood ◽  
Nashila Hirji ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Visual Cortex ◽  
Neural Plasticity ◽  
Treatment Strategies ◽  
Retinal Disease ◽  
Preliminary Evidence ◽  
Gene Therapies ◽  
Cone Function ◽  
Child Friendly

AbstractAchromatopsia (ACHM) is an inherited retinal disease characterised by complete loss of cone photoreceptor function from birth. In recent years, gene therapies have successfully been used to induce signal processing in dormant cones in animal models of ACHM, with greater functional benefits for younger animals. With several completed or on-going clinical trials of gene therapy for ACHM, preliminary evidence suggests that effects on visual function in adults with ACHM may be subtle. Given the known constraints of age on neural plasticity, it is possible that gene therapy earlier in life will have a greater impact. Sensitive, child-friendly tests of cone function are therefore needed to facilitate the optimisation of these treatment strategies. Here, we present a new method that leverages a multimodal approach, linking psychophysical estimates of cone function to cone-mediated signals in visual cortex, measured using fMRI. In a case study of two children with ACHM undergoing gene therapy, we find individual differences in recovery of cone function over time, with one child demonstrating strong concurrent evidence of improved cone function, and retinotopically organised responses in visual cortex to cone-selective stimuli. Integrated fMRI and psychophysical measures may provide insight into the utility of new sight-rescuing therapies at different stages of human development.

Nanostructured Hyaluronic Acid-based Materials for the Delivery of siRNA

2018 ◽  
Vol 24 (23) ◽  
pp. 2678-2691 ◽  
Author(s):  
Keval Shah ◽  
Sunita Chawla ◽  
Anuradha Gadeval ◽  
Goutham Reddy ◽  
Rahul Maheshwari ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Rna Interference ◽  
Sirna Delivery ◽  
Treatment Strategies ◽  
Aqueous Solubility ◽  
Micro Rna ◽  
Target Space ◽  
Significant Progress ◽  
Gene Therapies ◽  
Future Potential

Background: The search for the effective treatment strategies to combat a disease that is characterized by abnormal cell growth and known as cancer is still required to reach its destiny. To address the problem, recently several gene therapies based on novel RNA interference (RNAi) have been proposed such as siRNA, micro RNA, shRNA, etc. out of which, siRNAs (silencing RNA) promises to show significant progress in pharmacotherapy, including considerable expansion of the druggable target space and the possibility of treating cancer. Methods: This review aims to uncover the hyaluronic acid (HA) and HA-hybridized nanoplatforms for siRNA delivery systems with a particular focus on the discussion of available reports while addressing the future potential of HA-based treatment strategies. Results: HA modified siRNA delivery, as promised, provided better targeting potential in many types of cancers. In addition, it was able to modify the release of siRNA as well. Toxicity of HA is well mentioned however, the loophole is yet to be filled by exploring various remedies for overcoming toxicity. Conclusion: To overcome the problems associated with these emerging genetic tools, investigators have employed glycosaminoglycan HA-based biopolymers. This biopolymer offers a variety of properties such as biodegradability, biocompatibility, aqueous solubility, viscoelasticity, and non-immunogenicity.

scholarly journals Clinical Perspectives and Trends: Microperimetry as a trial endpoint in retinal disease

2021 ◽  
Author(s):  
Yesa Yang ◽  
Hannah Dunbar
Keyword(s):  
Clinical Trial ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Age Related ◽  
Wide Range ◽  
Trial Endpoints ◽  
Visual Acuity Loss ◽  
Psychophysical Test ◽  
Trial Endpoint

Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting early stages of common sight-threatening conditions such as age-related macular degeneration. Visual function measures are likely to be key candidates in this search. Over the last two decades, microperimetry has been used extensively to characterize functional vision in a wide range of retinal conditions, detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicenter trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical issues to consider, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.

scholarly journals The Ocular Gene Delivery Landscape

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1135
Author(s):  
Bhubanananda Sahu ◽  
Isha Chug ◽  
Hemant Khanna
Keyword(s):  
Gene Therapy ◽  
Genetic Diseases ◽  
Gene Therapies ◽  
Advantages And Disadvantages ◽  
Fda Approval ◽  
New Information ◽  
Efficient Delivery ◽  
Delivery Routes ◽  
History Of ◽  
Different Parts

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

scholarly journals Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 586
Author(s):  
Liam Cole ◽  
Diogo Fernandes ◽  
Maryam T. Hussain ◽  
Michael Kaszuba ◽  
John Stenson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Light Scattering ◽  
Dynamic Light Scattering ◽  
Viral Vector ◽  
Structural Characteristics ◽  
Genetic Material ◽  
Label Free ◽  
Gene Therapies ◽  
Multiple Challenges

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011–8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011–7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

The effect of a lollipop on vocally disruptive behavior in a patient with frontotemporal dementia: a case-study

2014 ◽  
Vol 26 (12) ◽  
pp. 2023-2026 ◽  
Author(s):  
W. F. Fick ◽  
J. P. van der Borgh ◽  
S. Jansen ◽  
R. T. C. M. Koopmans
Keyword(s):  
Beneficial Effect ◽  
Knowledge Base ◽  
Frontotemporal Dementia ◽  
Disruptive Behavior ◽  
Treatment Strategies ◽  
Limited Knowledge ◽  
People With Dementia

ABSTRACTA problematic and disturbing behavior which can develop in people with dementia, is vocally disruptive behavior (VDB). To date, the study of VDB is underdeveloped and with only a limited knowledge base. Medications commonly used in VDB have limited benefits and specific risks in patients with dementia. This report details the case of a patient with frontotemporal dementia with VDB, which responded very well by providing a lollipop. Subsequently, we pose theory-based hypotheses in order to try to explain the beneficial effect of this intervention. This may contribute to a better understanding of VDB and possible treatment strategies.

scholarly journals Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision

2021 ◽  
Vol 39 (4) ◽  
pp. 383-397
Author(s):  
Simone A. Huygens ◽  
Matthijs M. Versteegh ◽  
Stefan Vegter ◽  
L. Jan Schouten ◽  
Tim A. Kanters
Keyword(s):  
Gene Therapy ◽  
Economic Evaluation ◽  
Retinal Disease ◽  
Inherited Retinal Disease ◽  
Methodological Challenges

Beyond exposure therapy: formulation-based therapy treating a fear of urinary incontinence – a case study

2021 ◽  
pp. 1-5
Author(s):  
Torstein Stapley ◽  
Tracey Taylor ◽  
Victoria Bream
Keyword(s):  
Urinary Incontinence ◽  
Treatment Protocol ◽  
Treatment Strategies ◽  
Specific Phobia ◽  
Behaviour Therapy ◽  
Behavioural Treatment ◽  
Subjective Report ◽  
Cognitive Behaviour ◽  
Behavioural Factors

Abstract Background: The current literature on the specific phobia of urinary incontinence is limited, with no specific empirically established model or treatment protocol. Aims: This article consists of a case study of formulation-driven cognitive behaviour therapy (CBT) for phobia of urinary incontinence. Method: Martin attended a total of 12 treatment sessions. The treatment included the development of an idiosyncratic formulation, and the use of well-established cognitive and behavioural treatment strategies from other anxiety disorders. Results: Both outcome measures and Martin’s subjective report indicate that the treatment was effective. Conclusion: This case study contributes to the current limited literature on this phobia, and emphasises the importance of formulation-driven CBT to map for idiosyncratic features and target cognitive and behavioural factors.

ANALYSIS AGAINST ARREST SUSPECT IN POLICE REGULATION NO. 14 YEAR 2012 ON THE CRIME INVESTIGATION MANAGEMENT (CASE STUDY IN NORTH BOGOR POLICE)

2015 ◽  
Vol 1 (2) ◽  
pp. 76-92
Author(s):  
Dadang Suprijatna ◽  
Indralis Wardana ◽  
Fahrul Siregar
Keyword(s):  
Police Officers ◽  
Preliminary Evidence ◽  
Criminal Offense ◽  
Arrest Warrant ◽  
The Public ◽  
The North ◽  
The Republic ◽  
Search For Information ◽  
Management Case Study

ABSTRACTThe method used in this thesis is a normative juridical research that is the approach that uses the concept of positive legality which states that the law is identical with the norms made written and enacted by institutions or authorities. In addition this concept also saw law as a normative system that is autonomous, closed and detached from public life. For the purposes of the investigation, investigators at the behest of investigators authorized to make arrests also for the sake of the investigation, the investigator and the investigator maid authorities make arrests. Arrest order made against a person who alleged a criminal offense based on sufficient preliminary evidence. Execution of tasks arrests were made by police officers of the Republic of Indonesia by taking into account the Letter of Assignment and gives an arrest warrant that lists the suspect's identity and mentions the reason for arrest and brief descriptions of crimes that presupposed and place in check, in which case caught arrests made without warrants, provided that the catcher should be immediately handed caught and existing evidence to the investigator or the investigator's closest aides, ransom arrest warrant should be given to the family immediately after the arrest is done, can be done for a maximum of one day. The conclusion of this study are 1) The arrest of the perpetrators of the process by members of the police force North Bogor Police first is the start of the search for information, arrest / raids, searches of perpetrators, confiscation of evidence to facilitate the examination of the offender. 2) Barriers experienced by members of the North Bogor Police in the execution of the arrest of a criminal offense (a) Lack of cooperation between the police (investigators) to the public; (b) Perpetrators of the crime of removing traces of the crime; (c) Limited facilities and prasarana.yang owned by North Bogor Police; (d) .Terbatasnya human resources (police) to uncover a crime. 3) Efforts by the North Bogor Police to overcome the obstacles in the process of the arrest of perpetrators of criminal acts as follows: (a) Fix yourself to socialize paradigm shift to community policing. (b) Provide an opportunity for the whole society to provide input to the North Bogor Police. (c) Guidance personnel are able to provide persuasive measures. (d) Propose to the City Police Bogor on procurement operational support facilities.

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