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Tay-Sachs Disease

Tay–Sachs Disease (HEXA-related GM2 gangliosidosis variant B): Disease Characteristics Research Report

2026-04-25
Falcon MONDO:0010100 Model: Edison Scientific Literature 47 citations

Tay–Sachs Disease (HEXA-related GM2 gangliosidosis variant B): Disease Characteristics Research Report

Target Disease

1. Disease information

Concise overview (current understanding)

Tay–Sachs disease is an autosomal recessive GM2 gangliosidosis caused by deficiency of lysosomal β-hexosaminidase A (HexA), leading to progressive GM2 ganglioside accumulation in neurons and neurodegeneration (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2). Tay–Sachs is classically subdivided into infantile, juvenile, and late-/adult-onset clinical forms that correlate with residual HexA activity (gonzalezsanchez2025advancesindiagnosis pages 1-2, gonzalezsanchez2025advancesindiagnosis pages 2-4).

Direct abstract quotes (examples) - From a fetal-brain transcriptomics study (Feb 2023): the authors state they identified “dramatic changes in the transcriptome, suggesting a perturbation of normal development” and that fetal transcriptomes were “perturbed by 17 week’s gestation, suggesting abnormal neurodevelopment” (han2023geneexpressionchanges pages 1-3).

Key identifiers, synonyms, and alternative names

Table (click to expand)
Identifier system ID/code Preferred label Notes/source
OMIM (disease) 272800 Tay–Sachs disease Retrieved review explicitly lists OMIM 272800 for TSD; described as a rare autosomal recessive GM2 gangliosidosis caused by HEXA-related HexA deficiency (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2)
OMIM (gene) 606869 HEXA Retrieved primary study gives HEXA (MIM# 606869) as the causal gene encoding the alpha subunit of β-hexosaminidase A (ibrahim2023biochemicalandmutational pages 1-2)
Orphanet ORPHA:845 Tay–Sachs disease Retrieved review explicitly lists ORPHANET/Orphanet ORPHA845 for TSD (gonzalezsanchez2025advancesindiagnosis pages 1-2)
MeSH not found in retrieved sources Tay–Sachs disease MeSH identifier was not present in the retrieved evidence set used here; disease overview and synonyms supported by retrieved literature (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2)
ICD-10 not found in retrieved sources Tay–Sachs disease ICD-10 code not present in the retrieved evidence set used here (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2)
ICD-11 not found in retrieved sources Tay–Sachs disease ICD-11 code not present in the retrieved evidence set used here (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2)
MONDO not found in retrieved sources Tay–Sachs disease MONDO identifier was not present in the retrieved evidence set used here (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2)
Disease class / classification GM2 gangliosidosis variant B Tay–Sachs disease Retrieved sources state TSD is also known as GM2 gangliosidosis variant B and belongs to the GM2 gangliosidoses; inheritance is autosomal recessive (ibrahim2023biochemicalandmutational pages 1-2, picache2022therapeuticstrategiesfor pages 1-2)
Synonym — Tay–Sachs disease Common preferred disease name in all retrieved sources (gonzalezsanchez2025advancesindiagnosis pages 1-2, ibrahim2023biochemicalandmutational pages 1-2, picache2022therapeuticstrategiesfor pages 1-2)
Synonym — GM2 gangliosidosis variant B Explicit synonym in retrieved primary literature (ibrahim2023biochemicalandmutational pages 1-2)
Synonym — Hexosaminidase A deficiency Functional disease descriptor supported by retrieved sources describing HexA deficiency as the defining biochemical defect (gonzalezsanchez2025advancesindiagnosis pages 1-2, picache2022therapeuticstrategiesfor pages 1-2)

Table: This table summarizes key retrieved identifiers and synonyms for Tay–Sachs disease, including disease and gene OMIM entries, Orphanet ID, classification, and supported alternative names. It also flags identifier systems not found in the retrieved evidence so the final report can clearly distinguish confirmed versus missing mappings.

Evidence provenance

Most content here is derived from aggregated disease-level resources/reviews plus primary cohort studies and clinical trial registry records. Examples include a 2023 infantile Tay–Sachs cohort study in Egypt (Orphanet Journal of Rare Diseases) (ibrahim2023biochemicalandmutational pages 1-2), fetal brain transcriptomics (Journal of Inherited Metabolic Disease) (han2023geneexpressionchanges pages 1-3), and ClinicalTrials.gov records (NCT04798235 chunk 1).

2. Etiology

Disease causal factors

Risk factors

  • Genetic risk: carrier status for pathogenic HEXA variants; risk is elevated in some founder populations. A 2023 cohort paper summarizes carrier frequency being substantially higher in Ashkenazi Jewish populations (reported ~1/25) compared with ~1/250–300 in many other populations (ibrahim2023biochemicalandmutational pages 1-2).
  • Consanguinity: in a 2023 Egyptian infantile cohort, most affected children were born to consanguineous marriages (10/13) (ibrahim2023biochemicalandmutational pages 1-2).

Protective factors

No validated genetic or environmental protective factors were identified in the retrieved evidence set. A biologic “protective” concept is that higher residual HexA activity is associated with later onset and milder disease (i.e., acts as a functional modifier), but this is not a protective variant per se (gonzalezsanchez2025advancesindiagnosis pages 2-4).

Gene–environment interactions

No specific gene–environment interactions were identified in the retrieved evidence set; Tay–Sachs is best characterized as a monogenic disorder with phenotype strongly related to enzyme activity and variant class (gonzalezsanchez2025advancesindiagnosis pages 2-4).

3. Phenotypes

Phenotype spectrum and HPO mapping

Table (click to expand)
Subtype (with typical onset) Key clinical features (plain language) Suggested HPO terms (IDs and labels) Natural history/progression (including survival estimates) Frequency data (if available) Key sources
Infantile Tay–Sachs disease (typically 3–6 months) Initially normal infant, then irritability, mild motor weakness, exaggerated startle/hyperacusis, inability to sit, developmental regression, cherry-red macular spot, visual loss/blindness, feeding difficulty/dysphagia, seizures, later spasticity, dyskinesia, macrocephaly, cognitive decline, vegetative state HP:0001257 Spasticity; HP:0002376 Developmental regression; HP:0001344 Hyperreflexia; HP:0002072 Chorea/dyskinesia-related abnormal involuntary movements; HP:0001250 Seizure; HP:0000518 Cataract not appropriate / use HP:0010729 Cherry red spot of the macula; HP:0000407 Sensorineural hearing impairment / hyperacusis feature not directly matched here; HP:0002015 Dysphagia; HP:0000256 Macrocephaly; HP:0001252 Hypotonia Progressive neurodegeneration begins in the first year; cherry-red spot is typically present by ~6 months; vision loss develops by 12–18 months and many patients are blind by ~30 months; rapid worsening between ~8–10 months; tonic–myoclonic seizures often by ~12 months; later refractory seizures, dysphagia, decerebrate posturing, vegetative state; death usually at 2–5 years despite supportive care “More than two-thirds” require multiple anticonvulsants for seizure control; in one Egyptian cohort all 13/13 biochemically confirmed cases had infantile disease; Ashkenazi carrier frequency reported ~1/25 vs ~1/250–300 in many other populations (gonzalezsanchez2025advancesindiagnosis pages 9-11, ibrahim2023biochemicalandmutational pages 1-2, gonzalezsanchez2025advancesindiagnosis pages 2-4)
Juvenile / subacute Tay–Sachs disease (typically 2–10 years; some sources 3–5 years) Speech difficulty, clumsiness, gait problems, limb weakness, progressive spasticity, seizures, optic atrophy/vision decline; often more variable than infantile disease and may lack an early cherry-red spot HP:0002463 Speech impairment; HP:0002317 Unsteady gait; HP:0003324 Muscle weakness; HP:0001257 Spasticity; HP:0001250 Seizure; HP:0000648 Optic atrophy; HP:0002376 Developmental regression Intermediate course between infantile and adult forms; gradual neurologic deterioration over years with loss of motor function and increasing dependency; death commonly in adolescence or by mid-adolescence Specific phenotype frequencies were not provided in the retrieved juvenile-focused excerpts; review data cited elsewhere note limb weakness and ataxic gait as common, but no robust juvenile percentage table was available in retrieved primary evidence (gonzalezsanchez2025advancesindiagnosis pages 2-4, ibrahim2023biochemicalandmutational pages 1-2, sheth2018identificationofdeletionduplication pages 1-2)
Late-onset / adult Tay–Sachs disease (adolescence to adulthood; often 20s–30s) Slowly progressive muscle weakness, clumsy or ataxic gait, tremor, dysarthria/stuttering or other distinct speech changes, falls, difficulty climbing stairs, fatigue, cerebellar signs, triceps/quadriceps wasting, psychiatric symptoms including psychosis/delusions/impulsivity, mild cognitive or subcortical deficits HP:0001324 Muscle weakness; HP:0002066 Gait ataxia; HP:0001337 Tremor; HP:0001260 Dysarthria; HP:0002521 Cerebellar atrophy; HP:0007018 Falls; HP:0012378 Fatigue; HP:0000709 Psychosis; HP:0000738 Hallucinations/delusions-related psychiatric disturbance; HP:0002354 Memory impairment Chronic, slowly progressive course with prolonged survival; diagnostic delay is common; patients may first present to neuromuscular, movement-disorder, or psychiatric services; loss of ambulation may occur later and lifespan is variable Patient/caregiver burden study: muscle weakness 19/20 (95%), difficulty walking 19/20 (95%), falling 17/20 (85%), climbing stairs 16/20 (80%), “clumsy” gait 12/20 (60%), fatigue 10/20 (50%), coughing fits 5/20 (25%), GI issues 4/20 (20%); psychiatric symptoms may be the initial manifestation in up to half of patients (lyn2020patientandcaregiver pages 1-2, gonzalezsanchez2025advancesindiagnosis pages 4-5, barritt2017lateonsettay–sachsdisease pages 1-2, gonzalezsanchez2025advancesindiagnosis pages 2-4)

Table: This table summarizes Tay–Sachs disease manifestations across infantile, juvenile, and late-onset forms, linking clinical features to suggested HPO terms, natural history, and available frequency data. It is useful for phenotype curation, diagnostic support, and subtype-specific knowledge base entry development.

Quality-of-life impact (late-onset disease)

A qualitative study of late-onset GM2 gangliosidosis (including late-onset Tay–Sachs) quantified commonly reported symptoms and functional impacts. Frequently reported items included muscle weakness (95%), difficulty walking (95%), falling (85%), and difficulty climbing stairs (80%), emphasizing substantial impairment of mobility/independence and downstream psychosocial burden (lyn2020patientandcaregiver pages 1-2).

4. Genetic / molecular information

Causal gene(s)

Pathogenic variants (examples and variant types)

Functional consequences

Pathogenic HEXA variants generally produce loss of function by disrupting protein folding, heterodimer assembly, lysosomal trafficking, or catalytic function, ultimately preventing HexA-mediated hydrolysis of GM2 (ashiri2023usinganengineered pages 23-28, gonzalezsanchez2025advancesindiagnosis pages 7-9).

Modifier genes / epigenetics / chromosomal abnormalities

No robust modifier genes, epigenetic drivers, or chromosomal abnormalities specific to Tay–Sachs were identified in the retrieved evidence set.

5. Environmental information

Tay–Sachs is not established as an environmentally triggered disorder; no non-genetic causal environmental factors were identified in the retrieved evidence set.

6. Mechanism / pathophysiology

Core biochemical defect and causal chain

  1. HEXA loss-of-function causes deficient lysosomal HexA activity (gonzalezsanchez2025advancesindiagnosis pages 5-7, gonzalezsanchez2025advancesindiagnosis pages 7-9).
  2. HexA “specifically hydrolyzes the N-acetylgalactosamine residue in GM2 ganglioside,” and deficiency leads to “accumulation of GM2 gangliosides within lysosomes” (gonzalezsanchez2025advancesindiagnosis pages 7-9).
  3. GM2 accumulation contributes to lysosomal dysfunction (including lysosomal disruption) and neurodegeneration, with neuronal loss and gliosis (gonzalezsanchez2025advancesindiagnosis pages 7-9, gonzalezsanchez2025advancesindiagnosis pages 5-7).
  4. Downstream mechanisms include ER stress and apoptosis (neuron death) as well as neuroinflammation characterized by microglial activation and astrogliosis (gonzalezsanchez2025advancesindiagnosis pages 7-9, gonzalezsanchez2025advancesindiagnosis pages 9-11).

Neuroinflammation and glial involvement

A 2025 review states “astrogliosis has been identified as a critical component of GM2 gangliosidosis pathophysiology” and highlights that “astrocyte-microglia crosstalk is essential for amplifying neuroinflammatory responses” (gonzalezsanchez2025advancesindiagnosis pages 9-11). Candidate CSF inflammatory biomarkers for infantile disease include ENA-78, MCP-1, MIP-1α, MIP-1β, and TNFR2 (gonzalezsanchez2025advancesindiagnosis pages 9-11).

Myelin/oligodendrocyte involvement and biomarker data (large animal model)

In a sheep natural-history model (publication date Sep 2021; URL https://doi.org/10.1016/j.ymgme.2021.08.009), disease severity tracked with CSF GM2, MRI/MRS markers, and neuropathology including early oligodendrocyte loss and demyelination signatures (story2021naturalhistoryof pages 5-7). Reported MRS patterns included increased myoinositol (gliosis), increased taurine, increased choline-related markers (demyelination), and decreased NAA (neuronal/axonal integrity) (story2021naturalhistoryof pages 5-7).

Developmental stage mechanisms (human fetal brain)

A 2023 RNA-seq study of human fetal Tay–Sachs brain found transcriptomes “perturbed by 17 week’s gestation” and a “shift in the expression of the sphingolipid metabolic pathway away from production of the HEXA substrate, GM2 ganglioside,” implying compensatory remodeling and that developmental perturbations may precede overt neurodegeneration (han2023geneexpressionchanges pages 1-3).

Suggested ontology terms

7. Anatomical structures affected

Organ/system level

Tissue/cell level

Subcellular level

Suggested anatomical ontology terms

8. Temporal development

9. Inheritance and population

10. Diagnostics

Table (click to expand)
Test/approach Specimen What it measures Interpretation pitfalls Typical use case (diagnosis/carrier/prenatal) Notes Key sources
HexA/HexB enzyme activity assay using artificial substrates (e.g., MUG/MUGS with thermal differentiation) Leukocytes, serum, cultured skin fibroblasts, chorionic villi, dried blood spots, other cells/tissues/biological fluids Total hexosaminidase and HexA-specific activity; confirms biochemical deficiency Pseudodeficiency alleles can lower in vitro activity on synthetic substrates without causing disease; carrier detection by enzyme assay alone can be unreliable Primary diagnosis; confirmatory testing; prenatal when performed on fetal material Gold-standard confirmatory specimens in retrieved sources are fibroblasts, chorionic villi, or leukocytes; infantile disease often shows very low/absent activity, juvenile higher residual activity (gonzalezsanchez2025advancesindiagnosis pages 4-5, ashiri2023usinganengineered pages 23-28, gonzalezsanchez2025advancesindiagnosis pages 2-4) (gonzalezsanchez2025advancesindiagnosis pages 4-5, ashiri2023usinganengineered pages 23-28, gonzalezsanchez2025advancesindiagnosis pages 2-4)
Dried blood spot (DBS) HexA assay Dried blood spots Screening/initial biochemical detection of low HexA activity Positive/abnormal DBS requires confirmatory enzyme and molecular testing; not sufficient alone for definitive molecular characterization Early diagnosis; newborn/remote screening workflows; triage to confirmatory testing Reported as practical standard-of-care style primary test in one study; can be paired with sequencing/WES follow-up (bibi2021taysachsdiseasetwo pages 5-8, gonzalezsanchez2025advancesindiagnosis pages 2-4) (bibi2021taysachsdiseasetwo pages 5-8, gonzalezsanchez2025advancesindiagnosis pages 2-4)
Targeted HEXA variant analysis / common-variant panels Blood or genomic DNA Detects recurrent pathogenic alleles and selected adult-onset/pseudodeficiency alleles Limited if patient carries rare/private variants or CNVs; founder-focused panels may miss non-founder mutations Carrier screening; targeted diagnostic follow-up in high-risk populations Retrieved review notes panels including common null alleles plus adult-onset p.Gly269Ser and pseudodeficiency alleles p.Arg247Trp / p.Arg249Trp (gonzalezsanchez2025advancesindiagnosis pages 4-5) (gonzalezsanchez2025advancesindiagnosis pages 4-5)
Sanger sequencing of HEXA coding exons and splice junctions Genomic DNA from blood Single-nucleotide variants and small indels in coding/splice regions Can miss deep intronic/regulatory variants and exon-level deletions/duplications; partial detection only in some cohorts Diagnostic confirmation after low enzyme activity; family testing In the Egyptian infantile cohort, bidirectional Sanger sequencing had ~62% detection (8/13), prompting recommendation for broader NGS/CNV-aware workup when unresolved (ibrahim2023biochemicalandmutational pages 1-2) (ibrahim2023biochemicalandmutational pages 1-2)
Next-generation sequencing (targeted panels/WES; CNV-aware if possible) Genomic DNA Broad detection of HEXA variants, including rare/private pathogenic variants; may support broader differential diagnosis Requires variant interpretation; may still miss some structural/regulatory defects if CNV calling is inadequate Diagnosis of unresolved cases; family studies; carrier workup in diverse populations Recommended when Sanger is negative or only one pathogenic allele is found; WES identified novel homozygous HEXA variants in Pakistani/Moroccan families (bibi2021taysachsdiseasetwo pages 5-8, ibrahim2023biochemicalandmutational pages 1-2) (bibi2021taysachsdiseasetwo pages 5-8, ibrahim2023biochemicalandmutational pages 1-2)
MLPA (deletion/duplication analysis) Genomic DNA from whole blood Exon-level copy-number changes in HEXA Not designed for SNVs/small indels; usually used after sequencing fails to identify both alleles Diagnostic resolution of sequencing-inconclusive cases; family studies Detected homozygous exon 2-3 deletions, exon 1 deletions with a missense variant, and exon 1 duplication with splice variant; specifically recommended when one/both alleles are missing by sequencing (sheth2018identificationofdeletionduplication pages 2-3, sheth2018identificationofdeletionduplication pages 1-2) (sheth2018identificationofdeletionduplication pages 2-3, sheth2018identificationofdeletionduplication pages 1-2)
Prenatal enzyme testing on chorionic villi / chorionic villus sampling (CVS) Chorionic villi (typically 10-12 weeks) Fetal HexA activity and/or fetal genotype Requires correct parental interpretation and awareness of pseudodeficiency alleles; invasive procedure Prenatal diagnosis in at-risk pregnancies Retrieved review explicitly identifies CVS as a prenatal option and chorionic villi as a gold-standard specimen type for enzyme testing (gonzalezsanchez2025advancesindiagnosis pages 4-5, gonzalezsanchez2025advancesindiagnosis pages 2-4) (gonzalezsanchez2025advancesindiagnosis pages 4-5, gonzalezsanchez2025advancesindiagnosis pages 2-4)
Prenatal testing by amniocentesis Amniotic fluid/fetal cells (typically 15-18 weeks) Fetal genotype and/or biochemical testing depending laboratory workflow Same interpretive issues as other prenatal tests; invasive procedure Prenatal diagnosis in at-risk pregnancies Retrieved review gives amniocentesis at 15-18 weeks as an option when parental carrier status/risk is established (gonzalezsanchez2025advancesindiagnosis pages 4-5) (gonzalezsanchez2025advancesindiagnosis pages 4-5)
Carrier screening programs (premarital/preconception/community screening) Blood/DBS/DNA depending program Identifies heterozygous carriers to inform reproductive risk Enzyme-based carrier screening can be confounded by pseudodeficiency; molecular confirmation improves specificity Carrier screening; public health prevention In Ashkenazi Jewish communities, premarital carrier screening was associated with an approximately 95% reduction in Tay-Sachs incidence in retrieved evidence; historical founder frequencies are much higher than general-population rates (gonzalezsanchez2025advancesindiagnosis pages 2-4, ashiri2023usinganengineered pages 23-28) (gonzalezsanchez2025advancesindiagnosis pages 2-4, ashiri2023usinganengineered pages 23-28)
Integrated diagnostic workflow Start with leukocytes/fibroblasts/DBS, then DNA-based testing Combines biochemical confirmation with molecular definition of genotype Overreliance on a single modality can miss carriers, pseudodeficiency, or CNVs Best-practice diagnostic pathway Practical pathway from retrieved evidence: low HexA activity -> sequencing -> del/dup analysis/NGS if unresolved; use prenatal testing when familial pathogenic variants are known (gonzalezsanchez2025advancesindiagnosis pages 4-5, ibrahim2023biochemicalandmutational pages 1-2, sheth2018identificationofdeletionduplication pages 2-3) (gonzalezsanchez2025advancesindiagnosis pages 4-5, ibrahim2023biochemicalandmutational pages 1-2, sheth2018identificationofdeletionduplication pages 2-3)

Table: This table summarizes the main diagnostic and screening approaches for Tay-Sachs disease, including biochemical, molecular, prenatal, and carrier-screening methods. It highlights specimen types, what each test measures, common pitfalls such as pseudodeficiency alleles, and how these methods are used in real-world diagnostic pathways.

Real-world diagnostic implementation notes

11. Outcome / prognosis

12. Treatment

Table (click to expand)
Modality Example intervention Mechanism/rationale Evidence level (human/animal/in vitro) Key quantitative results Status/real-world use ClinicalTrials.gov IDs if applicable Key sources
In vivo gene therapy AAVrh8-HEXA + AAVrh8-HEXB (expanded-access; AXO-AAV-GM2 platform) Dual-vector replacement of both HexA subunits to restore CNS HexA activity; delivered intrathecally and/or intrathalamically because broad CNS distribution is required Human clinical + supporting animal studies In 2 infantile TSD patients, CSF HexA activity “nearly doubled from baseline and remained stable”; no vector-related AEs reported; one patient treated at 7 months showed MRI stabilization at 3 months but decline by 6 months; one older patient remained seizure-free at 4.5–5 years on same anticonvulsant regimen. Doses included 1×10^14 vg IT (75% cisterna magna, 25% thoracolumbar) and 4.2×10^13 vg combined thalamic+IT (flotte2022aavgenetherapy pages 1-6) First-in-human proof-of-concept; not approved Expanded access under IND 18225; follow-up study NCT06614569 (flotte2022aavgenetherapy pages 1-6, gonzalezsanchez2025advancesindiagnosis pages 15-17)
Interventional clinical trial, gene therapy AXO-AAV-GM2 dose-escalation study Same dual-AAV gene replacement strategy for infantile GM2 gangliosidosis/Tay-Sachs or Sandhoff disease Human clinical trial Phase 1; enrollment 9; trial status reported as TERMINATED in retrieved registry results (no efficacy outcomes in retrieved context) Clinical development program; not approved NCT04669535 (NCT04798235 chunk 1)
Interventional clinical trial, gene therapy TSHA-101 (AAV9 carrying HEXA and HEXB) One-time intrathecal AAV9 delivery of HEXA+HEXB to address HexA deficiency in infantile GM2 gangliosidosis Human clinical trial Active not recruiting; actual enrollment 3; outcomes include CSF/serum HexA activity, CHOP-INTEND, overall survival up to 5 years; quantitative efficacy not yet available in retrieved context Ongoing early-phase clinical development; not approved NCT04798235 (NCT04798235 chunk 1)
Substrate reduction therapy Miglustat Inhibits glycosphingolipid synthesis upstream to reduce GM2 substrate burden Animal + human clinical In mouse models, reduced brain GM2 by up to 50% and prolonged survival; in a 24-month study of 5 juvenile patients, did not halt neurological deterioration (gonzalezsanchez2025advancesindiagnosis pages 14-15) Off-label/experimental in GM2; not FDA-approved for Tay-Sachs NCT00418847; NCT00672022; NCT03822013 (gonzalezsanchez2025advancesindiagnosis pages 14-15, abidi2024metabolismofglycosphingolipids pages 85-90)
Next-generation substrate reduction therapy Nizubaglustat (AZ-3102) Small-molecule substrate reduction approach for GM2 gangliosidosis/NPC disease Human clinical trial Phase 2 recruiting; planned enrollment 21; no efficacy results yet in retrieved context Investigational NCT07399704 (NCT04798235 chunk 1)
Pharmacological chaperone Pyrimethamine Mutation-dependent stabilization/folding rescue of residual HexA, with BBB penetration In vitro + human clinical experience summarized in reviews Induced up to a threefold increase in enzymatic activity in TSD fibroblasts, but neurological benefit in patients has been limited/mutation-dependent (gonzalezsanchez2025advancesindiagnosis pages 14-15) Experimental/off-label; not standard disease-modifying therapy not provided in retrieved context (gonzalezsanchez2025advancesindiagnosis pages 14-15, ou2020anovelgene pages 11-11)
Enzyme replacement therapy Engineered human HexA / rhHexA Supplies exogenous enzyme to degrade stored GM2; major challenge is BBB/CNS delivery Animal + in vitro Engineered HexA degraded GM2 in Hexa-/- mouse-related systems and prevented severe storage in preclinical work; yeast-produced rhHexA reduced lysosomal mass and GM2 levels in patient fibroblasts/neuroglial cells after 72 h treatment (ashiri2023usinganengineered pages 23-28, abidi2024metabolismofglycosphingolipids pages 85-90) Preclinical; no approved ERT for Tay-Sachs not applicable (ashiri2023usinganengineered pages 23-28, abidi2024metabolismofglycosphingolipids pages 85-90, picache2022therapeuticstrategiesfor pages 1-2)
Recombinant enzyme production / cell studies Yeast-produced human recombinant lysosomal β-hexosaminidase A (rhHex-A) Scalable recombinant enzyme for cellular rescue of GM2 storage In vitro In patient and murine cell systems, 100 nM rhHexA for 72 h reduced lysosomal mass and GM2/LAMP1 colocalization; authors concluded rhHex-A “can efficiently degrade GM2 ganglioside and rescue lysosomal accumulation” Preclinical research only not applicable (abidi2024metabolismofglycosphingolipids pages 85-90)
Protein delivery across BBB Dual trojan horse HEXA protein (HEXA linked to BBB-entry motifs) Enzyme delivery strategy to shuttle HEXA across BBB, associate with HEXB, reach lysosomes, and reduce brain GM2 Animal + in vitro In adult LOTS-model mice, IV treatment reduced whole-brain GM2 by ~40% within 6 weeks and improved forelimb grip strength; also lowered GM2 in cultured human Tay-Sachs glial cells (osher2024treatinglateonsettay pages 1-2) Preclinical; not approved not applicable (osher2024treatinglateonsettay pages 1-2)
Broad therapeutic category HSCT / bone marrow transplantation Cross-correction via donor-derived enzyme-producing cells Human case series/reviewed clinical experience Can increase systemic HexA; reported survival prolongation in some cases, but overall insufficient CNS correction and no consistent motor improvement (gonzalezsanchez2025advancesindiagnosis pages 14-15) Not established as effective disease-modifying standard for Tay-Sachs CNS disease not provided in retrieved context (gonzalezsanchez2025advancesindiagnosis pages 14-15, gonzalezsanchez2025advancesindiagnosis pages 15-17)
Emerging pathway-targeted SRT B4GALNT1 / GM2 synthesis inhibition (e.g., lead compound QT163) Directly target GM2 synthesis pathway to reduce GM2 and lyso-GM2 production Preclinical in vitro/drug discovery Lead compound QT163 showed strongest inhibition with reported IC50 0.2 mM; lyso-GM2 proposed as biomarker for diagnosis/treatment monitoring (abidi2024metabolismofglycosphingolipids pages 85-90) Experimental discovery-stage not applicable (abidi2024metabolismofglycosphingolipids pages 85-90)

Table: This table summarizes major therapeutic modalities and clinical-trial programs for Tay-Sachs/GM2 gangliosidosis, including current human gene-therapy studies, substrate-reduction approaches, pharmacological chaperones, and preclinical enzyme/protein-delivery strategies. It is useful for comparing mechanism, evidence maturity, quantitative outcomes, and current development status across the treatment landscape.

Key recent developments (prioritizing 2023–2024 sources)

Human gene therapy evidence (first-in-human)

A first-in-human expanded-access experience (Nature Medicine version published Feb 2022; preprint posted Feb 18, 2021; URL https://doi.org/10.1038/s41591-021-01664-4; preprint URL https://doi.org/10.21203/rs.3.rs-195847/v1) reported intrathecal and intrathalamic delivery of AAVrh8-HEXA plus AAVrh8-HEXB in two infantile Tay–Sachs patients, with no vector-related adverse events and increased CSF HexA activity; MRI and seizure outcomes suggested partial/temporary deviation from expected infantile natural history in the younger-treated child (flotte2022aavgenetherapy pages 1-6).

Figure evidence: the treatment-associated HexA activity trajectories and delivery-route imaging are shown in retrieved figure/table regions from the case report (flotte2022aavgenetherapy media 379a08f6, flotte2022aavgenetherapy media 8b29bbe4, flotte2022aavgenetherapy media 4f87ceb4, flotte2022aavgenetherapy media c9927c10).

MAXO term suggestions (examples)

13. Prevention

14. Other species / natural disease

  • Naturally occurring large-animal model: Jacob sheep with a naturally occurring HEXA missense mutation develop progressive neurologic disease and GM2 accumulation; the model enables biomarker and therapeutic evaluation at a large-brain scale (story2021naturalhistoryof pages 1-2, story2021naturalhistoryof pages 5-7).
  • Additional natural disease has been described in other species (e.g., cats/dogs; wild boar variants mentioned in a compilation), but detailed comparative pathology was not comprehensively extractable from the retrieved evidence set (ashiri2023usinganengineered pages 129-133).

15. Model organisms

Limitations of this report (evidence availability)

  • ICD-10/ICD-11/MeSH/MONDO identifiers were not present in the retrieved evidence set and therefore are explicitly not populated to avoid hallucination (artifact-00).
  • Several key references in this area exist but were not retrievable within this tool run; consequently, some sections (e.g., global epidemiology by region, comprehensive variant frequency from gnomAD, formal clinical guidelines, and late-2024 Neurology Genetics diagnostic paper) could not be exhaustively covered.

References

  1. (gonzalezsanchez2025advancesindiagnosis pages 1-2): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  2. (ibrahim2023biochemicalandmutational pages 1-2): Doaa M. A. Ibrahim, Ola S. M. Ali, Hala Nasr, Ekram Fateen, and Alice AbdelAleem. Biochemical and mutational analyses of hexa in a cohort of egyptian patients with infantile tay-sachs disease. expansion of the mutation spectrum. Orphanet Journal of Rare Diseases, Mar 2023. URL: https://doi.org/10.1186/s13023-023-02637-1, doi:10.1186/s13023-023-02637-1. This article has 13 citations and is from a peer-reviewed journal.

  3. (gonzalezsanchez2025advancesindiagnosis pages 2-4): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  4. (han2023geneexpressionchanges pages 1-3): Sangwoo T. Han, Ashley Hirt, Elena‐Raluca Nicoli, Mari Kono, Camilo Toro, Richard L. Proia, and Cynthia J. Tifft. Gene expression changes in tay–sachs disease begin early in fetal brain development. Journal of Inherited Metabolic Disease, 46:687-694, Feb 2023. URL: https://doi.org/10.1002/jimd.12596, doi:10.1002/jimd.12596. This article has 10 citations and is from a peer-reviewed journal.

  5. (picache2022therapeuticstrategiesfor pages 1-2): Jaqueline A. Picache, Wei Zheng, and Catherine Z. Chen. Therapeutic strategies for tay-sachs disease. Frontiers in Pharmacology, Jul 2022. URL: https://doi.org/10.3389/fphar.2022.906647, doi:10.3389/fphar.2022.906647. This article has 40 citations.

  6. (NCT04798235 chunk 1): Dr. Anupam Sehgal. First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis. Dr. Anupam Sehgal. 2021. ClinicalTrials.gov Identifier: NCT04798235

  7. (gonzalezsanchez2025advancesindiagnosis pages 5-7): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  8. (gonzalezsanchez2025advancesindiagnosis pages 7-9): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  9. (ashiri2023usinganengineered pages 16-23): M Ashiri. Using an engineered human hexosaminidase as an enzyme replacement therapy to treat a mouse model of tay-sachs disease. Unknown journal, 2023.

  10. (gonzalezsanchez2025advancesindiagnosis pages 9-11): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  11. (sheth2018identificationofdeletionduplication pages 1-2): Jayesh Sheth, Mehul Mistri, Lakshmi Mahadevan, Sanjeev Mehta, Dhaval Solanki, Mahesh Kamate, and Frenny Sheth. Identification of deletion-duplication in hexa gene in five children with tay-sachs disease from india. BMC Medical Genetics, Jul 2018. URL: https://doi.org/10.1186/s12881-018-0632-7, doi:10.1186/s12881-018-0632-7. This article has 11 citations and is from a peer-reviewed journal.

  12. (lyn2020patientandcaregiver pages 1-2): Nicole Lyn, Ruth Pulikottil-Jacob, Camille Rochmann, Robert Krupnick, Chad Gwaltney, Nick Stephens, Julie Kissell, Gerald F. Cox, Tanya Fischer, and Alaa Hamed. Patient and caregiver perspectives on burden of disease manifestations in late-onset tay-sachs and sandhoff diseases. Orphanet Journal of Rare Diseases, Apr 2020. URL: https://doi.org/10.1186/s13023-020-01354-3, doi:10.1186/s13023-020-01354-3. This article has 19 citations and is from a peer-reviewed journal.

  13. (gonzalezsanchez2025advancesindiagnosis pages 4-5): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  14. (barritt2017lateonsettay–sachsdisease pages 1-2): Andrew W Barritt, Stuart J Anderson, P Nigel Leigh, and Basil H Ridha. Late-onset tay–sachs disease. Practical Neurology, 17:396-399, Jul 2017. URL: https://doi.org/10.1136/practneurol-2017-001665, doi:10.1136/practneurol-2017-001665. This article has 38 citations and is from a peer-reviewed journal.

  15. (sheth2018identificationofdeletionduplication pages 2-3): Jayesh Sheth, Mehul Mistri, Lakshmi Mahadevan, Sanjeev Mehta, Dhaval Solanki, Mahesh Kamate, and Frenny Sheth. Identification of deletion-duplication in hexa gene in five children with tay-sachs disease from india. BMC Medical Genetics, Jul 2018. URL: https://doi.org/10.1186/s12881-018-0632-7, doi:10.1186/s12881-018-0632-7. This article has 11 citations and is from a peer-reviewed journal.

  16. (ashiri2023usinganengineered pages 23-28): M Ashiri. Using an engineered human hexosaminidase as an enzyme replacement therapy to treat a mouse model of tay-sachs disease. Unknown journal, 2023.

  17. (story2021naturalhistoryof pages 5-7): Brett Story, Toloo Taghian, Jillian Gallagher, Jey Koehler, Amanda Taylor, Ashley Randle, Kayly Nielsen, Amanda Gross, Annie Maguire, Sara Carl, Siauna Johnson, Deborah Fernau, Elise Diffie, Paul Cuddon, Carly Corado, Sundeep Chandra, Miguel Sena-Esteves, Edwin Kolodny, Xuntian Jiang, Douglas Martin, and Heather Gray-Edwards. Natural history of tay-sachs disease in sheep. Molecular Genetics and Metabolism, 134:164-174, Sep 2021. URL: https://doi.org/10.1016/j.ymgme.2021.08.009, doi:10.1016/j.ymgme.2021.08.009. This article has 13 citations and is from a peer-reviewed journal.

  18. (bibi2021taysachsdiseasetwo pages 5-8): Farah Bibi, Asmat Ullah, Thomas Bourinaris, Stephanie Efthymiou, Yamna Kriouile, Tipu Sultan, Shahzad Haider, Vincenzo Salpietro, Henry Houlden, and Ghazala Kaukab Raja. Tay-sachs disease: two novel rare hexa mutations from pakistan and morocco. Klinische Pädiatrie, 233:226-230, Apr 2021. URL: https://doi.org/10.1055/a-1371-1561, doi:10.1055/a-1371-1561. This article has 17 citations.

  19. (flotte2022aavgenetherapy pages 1-6): Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, and Miguel Sena-Esteves. Aav gene therapy for tay-sachs disease. Nature Medicine, 28:251-259, Feb 2022. URL: https://doi.org/10.1038/s41591-021-01664-4, doi:10.1038/s41591-021-01664-4. This article has 155 citations and is from a highest quality peer-reviewed journal.

  20. (gonzalezsanchez2025advancesindiagnosis pages 15-17): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  21. (gonzalezsanchez2025advancesindiagnosis pages 14-15): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  22. (abidi2024metabolismofglycosphingolipids pages 85-90): I Abidi. Metabolism of glycosphingolipids and targeting gm2 synthesis pathway to develop substrate reduction approach in tay-sachs and sandhoff disorders. Unknown journal, 2024.

  23. (ou2020anovelgene pages 11-11): Li Ou, Michael J. Przybilla, Alexandru-Flaviu Tăbăran, Paula Overn, M. Gerard O’Sullivan, Xuntian Jiang, Rohini Sidhu, Pamela J. Kell, Daniel S. Ory, and Chester B. Whitley. A novel gene editing system to treat both tay–sachs and sandhoff diseases. Gene Therapy, 27:226-236, Jan 2020. URL: https://doi.org/10.1038/s41434-019-0120-5, doi:10.1038/s41434-019-0120-5. This article has 70 citations and is from a peer-reviewed journal.

  24. (osher2024treatinglateonsettay pages 1-2): Esther Osher, Yossi Anis, Ruth Singer-Shapiro, Nataly Urshanski, Tamar Unger, Shira Albeck, Oren Bogin, Gary Weisinger, Fortune Kohen, Avi Valevski, Aviva Fattal-Valevski, Liora Sagi, Michal Weitman, Yulia Shenberger, Nadav Sagiv, Ruth Navon, Meir Wilchek, and Naftali Stern. Treating late-onset tay sachs disease: brain delivery with a dual trojan horse protein. Molecular Therapy - Methods & Clinical Development, 32:101300, Sep 2024. URL: https://doi.org/10.1016/j.omtm.2024.101300, doi:10.1016/j.omtm.2024.101300. This article has 5 citations.

  25. (flotte2022aavgenetherapy media 379a08f6): Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, and Miguel Sena-Esteves. Aav gene therapy for tay-sachs disease. Nature Medicine, 28:251-259, Feb 2022. URL: https://doi.org/10.1038/s41591-021-01664-4, doi:10.1038/s41591-021-01664-4. This article has 155 citations and is from a highest quality peer-reviewed journal.

  26. (flotte2022aavgenetherapy media 8b29bbe4): Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, and Miguel Sena-Esteves. Aav gene therapy for tay-sachs disease. Nature Medicine, 28:251-259, Feb 2022. URL: https://doi.org/10.1038/s41591-021-01664-4, doi:10.1038/s41591-021-01664-4. This article has 155 citations and is from a highest quality peer-reviewed journal.

  27. (flotte2022aavgenetherapy media 4f87ceb4): Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, and Miguel Sena-Esteves. Aav gene therapy for tay-sachs disease. Nature Medicine, 28:251-259, Feb 2022. URL: https://doi.org/10.1038/s41591-021-01664-4, doi:10.1038/s41591-021-01664-4. This article has 155 citations and is from a highest quality peer-reviewed journal.

  28. (flotte2022aavgenetherapy media c9927c10): Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, and Miguel Sena-Esteves. Aav gene therapy for tay-sachs disease. Nature Medicine, 28:251-259, Feb 2022. URL: https://doi.org/10.1038/s41591-021-01664-4, doi:10.1038/s41591-021-01664-4. This article has 155 citations and is from a highest quality peer-reviewed journal.

  29. (story2021naturalhistoryof pages 1-2): Brett Story, Toloo Taghian, Jillian Gallagher, Jey Koehler, Amanda Taylor, Ashley Randle, Kayly Nielsen, Amanda Gross, Annie Maguire, Sara Carl, Siauna Johnson, Deborah Fernau, Elise Diffie, Paul Cuddon, Carly Corado, Sundeep Chandra, Miguel Sena-Esteves, Edwin Kolodny, Xuntian Jiang, Douglas Martin, and Heather Gray-Edwards. Natural history of tay-sachs disease in sheep. Molecular Genetics and Metabolism, 134:164-174, Sep 2021. URL: https://doi.org/10.1016/j.ymgme.2021.08.009, doi:10.1016/j.ymgme.2021.08.009. This article has 13 citations and is from a peer-reviewed journal.

  30. (ashiri2023usinganengineered pages 129-133): M Ashiri. Using an engineered human hexosaminidase as an enzyme replacement therapy to treat a mouse model of tay-sachs disease. Unknown journal, 2023.

  31. (picache2022therapeuticstrategiesfor pages 6-8): Jaqueline A. Picache, Wei Zheng, and Catherine Z. Chen. Therapeutic strategies for tay-sachs disease. Frontiers in Pharmacology, Jul 2022. URL: https://doi.org/10.3389/fphar.2022.906647, doi:10.3389/fphar.2022.906647. This article has 40 citations.

  32. (gonzalezsanchez2025advancesindiagnosis pages 11-12): María González-Sánchez, María Jesús Ramírez-Expósito, and José Manuel Martínez-Martos. Advances in diagnosis, pathological mechanisms, clinical impact, and future therapeutic perspectives in tay–sachs disease. Neurology International, 17:98, Jun 2025. URL: https://doi.org/10.3390/neurolint17070098, doi:10.3390/neurolint17070098. This article has 4 citations.

  33. (taghian2025fiveyearanalysisof pages 1-2): Toloo Taghian, Jillian Gallagher, Stephanie Bertrand, William C. Baker, Kalajan Lopez Mercado, Hector R. Benatti, Erin Hall, Yvette Lopez, Abigail McElroy, John T. McCarthy, Sanjana Pulaparthi, Deborah Fernau, Samuel Mather, Sophia Esteves, Elise Diffie, Amanda Gross, Hannah G. Lahey, Xuntian Jiang, Elizabeth Parsley, Rachael Gately, Rachel Prestigiacomo, Siauna Johnson, Amanda Taylor, Lindsey Bierfeldt, Susan Tuominen, Jennifer Koehler, Guangping Gao, Jun Xie, Qin Su, Robert King, Matthew J. Gounis, Vania Anagnostakou, Ajit Puri, Ana Rita Batista, Miguel Sena-Esteves, Douglas R. Martin, and Heather Gray-Edwards. Five-year analysis of efficacy and safety of a bidirectional aav gene therapy in tay-sachs sheep. Journal of Clinical Investigation, Sep 2025. URL: https://doi.org/10.1172/jci182942, doi:10.1172/jci182942. This article has 0 citations and is from a highest quality peer-reviewed journal.