Drug Database
HS

HSV-tk gene therapy (HSVtk / Zalmoxis / TK therapy)

✓ Approved

Megapharm Ltd · POLA1 · Cell-based Therapies

What is HSV-tk gene therapy?

HSV-tk gene therapy is a cell-based therapies developed by Megapharm Ltd. It is approved for therapeutic indications via injectable (others) or intravenous (iv).

Drug Profile

Brand NamesHSVtk, Zalmoxis, TK therapy
CompanyMegapharm Ltd
Drug ClassCell-based Therapies, Gene Therapy
Molecular TargetPOLA1
RouteInjectable (Others), Intravenous (IV)
StatusApproved
Sources: ClinicalTrials.gov, Megapharm Ltd

Mechanism of Action

Molecular Targets

HSV-tk gene therapy acts on 1 molecular target:

POLA1DNA polymerase alpha 1, catalytic subunit (PDR, POLA)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

HSV-tk gene therapy is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Immune system disordersChronic graft versus host disease✓ Approved

Related Research Articles

PubMedSpartan medical research journal2026-08-30

Polymorphic mimicry - When Herpes Isn't Just Herpes: Genital Herpes Mimicking Secondary Syphilis: A Case Report.

Vierra Andrew A, Jamal Leena L, Bokhari Khadijah K, Makki Adam A et al.

Herpes simplex virus type 2 (HSV-2) is a highly prevalent sexually transmitted infection (STI), affecting approximately 13% of the global population. While classic presentations involve painful vesicular clusters, HSV-2 can present atypically or trigger immune-mediated reactions like erythema multiforme (EM). These polymorphic presentations can mimic other STIs, particularly secondary syphilis, leading to diagnostic momentum and delayed appropriate therapy. A 47-year-old male with a history of recurrent genital ulcers presented to the emergency department with worsening penile lesions, anal pain, and a new onset rash on his palms and soles. He had been treated for presumed syphilis two months prior. Examination revealed vesiculopustular genital lesions, inguinal lymphadenopathy, perianal ulcers resembling fissures, and targetoid lesions on the extremities. The clinical triad of genital ulcers, anal pathology, and a palmoplantar rash strongly suggested secondary syphilis. However, syphilis serology returned negative. Polymerase chain reaction (PCR) testing confirmed HSV-2. The acral rash was diagnosed as EM secondary to HSV. The patient was diagnosed with HSV-2 proctitis and HSV-associated erythema multiforme. He was treated with high-dose valacyclovir. At the two-week follow-up, genital and anal lesions had healed, and the systemic rash had resolved. HSV-associated erythema multiforme can produce a clinical picture indistinguishable from secondary syphilis. Emergency clinicians must maintain a broad differential for genital ulcers with acral rashes. PCR testing is superior to syndromic diagnosis in complex presentations to prevent unnecessary antibiotic exposure and ensure timely antiviral management.

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PubMedMolecular therapy. Nucleic acids2026-08-30

MicroRNA-sensing plasmid system for dynamic control of functional ion channel expression.

Geuter Joschua J, Austin Thomas T TT, Corke Jack J, Tian Naxi N et al.

Gene therapy offers the potential for long-term treatment of a range of chronic diseases. However, permanent gene therapy expression may not be desirable. Efforts have been made to create systems that can be switched on/off by stimuli including light, designer drugs, or cellular contexts including increased electrical activity. Here, we designed a plasmid system in which ion channel expression and function are regulated by microRNA (miR)-an endogenous class of short noncoding RNAs which negatively regulate gene expression. We modified an existing voltage-gated potassium channel gene therapy with a binding cassette for miR-193a-3p, and transfected this "miR-193-OFF" system in neuro2A cells. Co-transfection with an inhibitor or mimic of miR-193a-3p, respectively, enhanced or repressed expression of our transgene, assessed using a GFP marker. Using whole-cell voltage clamp, we observed tuneable voltage-gated potassium currents in cells co-transfected with a miR-193a-3p inhibitor/mimic, compared with a non-targeting control oligonucleotide. Together, this demonstrates the concept of a miR-mediated molecular switch which can bias therapeutic ion channel expression based on a specific miR signal. As miRs are a ubiquitous molecular mechanism, our approach could be applied to a wide range of cellular and disease contexts, potentially expanding gene therapy to new patient populations.

PMID 42668707
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PubMedJAMA2026-08-30

Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy: A Meta-Analysis of Outcomes Trials.

Gillmore Julian D JD, Hamatani Yasuhiro Y, Fontana Marianna M, Vaduganathan Muthiah M et al.

Gene-silencing therapies reduce hepatic transthyretin (TTR) production and have been evaluated in phase 3 trials in TTR amyloid cardiomyopathy (ATTR-CM). However, differences in trial design and background therapies have limited assessment of the overall treatment effect and its consistency according to baseline TTR stabilizer use. To assess the effect of TTR gene-silencing therapies in patients with ATTR-CM. PubMed was searched through June 15, 2026, for randomized, placebo-controlled, phase 3 outcome trials of gene-silencing therapies in ATTR-CM. Two reviewers independently extracted data, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Fixed-effects meta-analysis estimated rate ratios (RRs) or hazard ratios (HRs) with 95% CIs. The prespecified primary outcome was the composite of all-cause mortality and recurrent cardiovascular events. Secondary outcomes included all-cause mortality, cardiovascular death, time to first primary outcome, functional capacity (6-minute walk distance), and health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary Score). A total of 2 studies (HELIOS-B and CARDIO-TTRansform) met the inclusion criteria and included 2086 patients with ATTR-CM. The studies included 1902 men with a median age of 77 years (range for HELIOS-B, 45-85 years; for CARDIO-TTRansform, 41-91 years). Gene-silencing therapy reduced the primary end point by 20% (RR, 0.80; 95% CI, 0.69-0.94; P = .006), with no heterogeneity between trials (P for heterogeneity = .28). Gene-silencing therapy also reduced the risk of all-cause death (HR, 0.74; 95% CI, 0.61-0.91) and time to first all-cause death or cardiovascular events (HR, 0.77; 95% CI, 0.67-0.89) compared with placebo. Gene silencers preserved 6-minute walk distance (placebo-corrected difference, +22.2 m; 95% CI, 14.3-30.0) and Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (+4.5; 95% CI, 2.7-6.2), with no evidence of between-trial heterogeneity. Treatment effects on primary end points differed according to baseline stabilizer use, with significant benefits observed among patients not receiving background stabilizer therapy (RR, 0.69; 95% CI, 0.57-0.85) and no significant incremental benefit observed for those receiving concomitant stabilizer at baseline (RR, 0.97; 95% CI, 0.77-1.23; P for heterogeneity = .03). Similar heterogeneity was observed for functional capacity and health status. The findings from this meta-analysis support TTR gene silencing for ATTR-CM. The attenuated benefit observed for patients receiving concomitant TTR stabilizer therapy may reflect residual differences in case mix, disease duration, or magnitude of TTR suppression or a true ceiling on additional benefit of gene silencing in the setting of background TTR stabilization. PROSPERO registration: CRD420261421656. ClinicalTrials.gov Identifier: HELIOS-B, NCT04153149; and CARDIO-TTRansform, NCT04136171.

PMID 42669065
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PubMedGenes & diseases2026-08-30

A comprehensive review on apoptotic miRNAs and antagomiRs in breast cancer: Enhancing radio sensitization.

Najafi-Amiri Maryam M, Pourhabib-Mamaghani Mina M, Aghaee-Bakhtiari Seyed Hamid SH, Bahreyni-Toossi Mohammad-Taghi MT et al.

Breast cancer (BC) is the most fatal cancer in women worldwide, and in spite of progresses in cancer treatment methods, its therapy has remained as a primary health issue. Inadequate apoptosis level is one of the main reasons of radiotherapy and chemotherapy resistance in lots of cancers including BC. Besides, gene therapy is one of new methods which has been proposed and developed in recent decades for various diseases diagnosis and treatment containing cancer. Since changes in miRs level which are one of different types of RNA molecules have been proved in assorted diseases, they are utilized as a gene therapy agent in order to make influence in diverse signaling pathways which are effective in unappealing biological alteration. In lots of studies, miRs' role in apoptosis pathway in combination with radiotherapy, chemotherapy or solely have been investigated. Many miRNAs and anti-miRNAs have been demonstrated as radiosensitizers/radioresistance agents and chemosensitisers/chemoresistance agents through apoptosis cell death pathways, and numerous miRs have been introduced as apoptotic regulators and they have a good potential to be radiosensitizers and their role in these pathways must be investigated. In the current review, we have tried to investigate and summarize radiosensitizer and radioresistant miRs and anti-microRNAs (anti-miRs) which have been utilized in BC.

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PubMedAmerican journal of ophthalmology2026-08-30

Biomaterials in Retinal Surgery: Engineering the Future.

Dindar Ismail Ahmed IA, Shoichet Molly S MS, Labriola Jonathan J, Forman Adam A et al.

To review current and emerging biomaterials in retinal surgery - vitreous tamponade agents, retinal prostheses, retinal pigment epithelium (RPE) transplant scaffolds, intraocular drug delivery platforms, and gene therapy vectors - with emphasis on the authors' oxime-crosslinked hyaluronic acid vitreous substitute. Narrative expert review. Systematic review methodology was not used; no protocol registration, pre-specified eligibility criteria, dual independent screening, or PRISMA flow diagram was undertaken. Published preclinical animal studies, Phase I-III clinical trials, US Food and Drug Administration approvals, and real-world evidence on biomaterials in posterior segment surgery. No individual patient data were accessed. A structured literature search of PubMed/MEDLINE, supplemented by Google Scholar, was performed from January 2018 to March 2026 across five domains: vitreous tamponade agents; retinal prostheses; scaffold-based RPE transplantation; nanoparticle and sustained-release drug delivery; and gene therapy vectors. Peer-reviewed investigations, trial reports, and regulatory data were prioritized. The authors' preclinical hydrogel data are presented as original data within a review context. Best-corrected visual acuity, intraocular pressure, electroretinography, retinal microstructure on optical coherence tomography, prosthetic visual acuity, ellipsoid zone area loss, injection frequency, and in vivo biocompatibility. The PRIMA photovoltaic subretinal implant produced a clinically meaningful improvement in visual acuity in 26 of 32 patients (81%) with geographic atrophy at 12 months. A 44-channel suprachoroidal prosthesis showed no device-related serious adverse events at 2.7 years. The authors' oxime-crosslinked hyaluronic acid hydrogel demonstrated density 1.01 g/mL and refractive index 1.356, with preserved electroretinography and intraocular pressure of 13.5-25.9 mmHg in rabbits. Scaffold-based RPE transplantation has entered Phase I/IIa trials. 2025 approvals included a refillable ranibizumab port delivery system for diabetic retinopathy and the first encapsulated cell therapy implant for macular telangiectasia type 2. Three Phase 3 anti-VEGF gene therapy trials are ongoing. Biomaterial engineering is transforming retinal disease management from stabilization toward tissue replacement and vision restoration. Principal limitations are the preclinical status of the hydrogel data and early-phase status of RPE scaffold trials. Outstanding challenges include long-term in vivo stability, immunological management of allogeneic constructs, scalable manufacturing, and definitive efficacy trials.

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SGLT2 inhibitor therapy is associated with IL-10/TGF-α/sVEGFR3 signalling and adipose tissue remodelling in advanced heart failure.

Cinkajzlova Anna A, Kasperova Barbora Judita BJ, Ivak Peter P, Netuka Ivan I et al.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardioprotective effects in heart failure (HF), yet the molecular mechanisms underlying these benefits remain incompletely understood. This study aimed to characterize cardioprotective effects of SGLT2i, changes of circulating growth and inflammatory factors, as well as adipose tissue gene expression, in subjects with advanced HF (stage D). 27 subjects with HF undergoing cardiovascular surgery were included, comprising 17 subjects treated with SGLT2i and 10 untreated controls. Soluble factors were analysed using Luminex assay, and mRNA expression in subcutaneous (SAT) and epicardial adipose tissue (EAT) was assessed. Subjects receiving SGLT2i exhibited a non-significant trend toward lower BNP concentrations (329.1 ± 78.7 vs. 514.2 ± 103.8 pmol/L, p = 0.079) and increased circulatory levels of anti-inflammatory IL-10 (7.2 ± 0.4 vs. 5.8 ± 0.7 pg/mL, p = 0.025) and cardioprotective TGF-α (3.5 ± 0.3 vs. 2.7 ± 0.4 pg/mL, p = 0.039). sVEGFR3 levels (82.3 ± 4.7 vs. 63.3 ± 3.9 pg/mL, p = 0.010) were higher in SGLT2i, suggesting altered lymphangiogenic signalling. Transcriptomic analysis showed lower expression of genes associated with inflammation (IL6, CCL2, CXCL2), cardiac hypertrophy (PKFP, NAMPT), fibrosis (TNC, TNFAIP3), and cellular senescence (ICAM1, CDKN1A), predominantly in SAT. SGLT2i therapy in advanced HF was associated with higher circulating IL-10, TGF-α and sVEGFR3 levels and with a more favourable adipose tissue gene expression profile characterized by lower expression of genes related to inflammation, fibrosis, and cellular senescence. These findings identify molecular pathways associated with SGLT2i therapy that warrant further mechanistic investigation.

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