Canavan Disease (Aspartoacylase deficiency) — Disease Characteristics Research Report

Executive summary (current understanding)

Canavan disease (CD) is an ultra-rare, typically early-infantile onset leukodystrophy caused by biallelic loss-of-function variants in ASPA, leading to deficient aspartoacylase activity and pathologic accumulation of N-acetyl-L-aspartate (NAA), with characteristic spongiform degeneration/vacuolation and dys-/hypomyelination in CNS white matter. (bley2021thenaturalhistory pages 1-2, corti2023adenoassociatedvirusmediatedgene pages 1-2, grønbækthygesen2024cellularandmolecular pages 1-2)

1. Disease information

1.1 What is the disease?

Canavan disease is a severe neurodegenerative leukodystrophy characterized histologically by insufficient myelination with progressive spongy degeneration of brain white matter. (bley2021thenaturalhistory pages 1-2)

1.2 Key identifiers (cross-references)

• OMIM/MIM (disease): MIM #271900 (bley2021thenaturalhistory pages 1-2)
• OMIM (gene): ASPA (OMIM 608034) (matalon2002canavandiseaseprenatal pages 14-16)
• ClinicalTrials.gov (active gene therapy trials): NCT04998396; NCT04833907 (NCT04998396 chunk 1, NCT04833907 chunk 1)
• MONDO ID: Not identified in the retrieved primary literature corpus; should be added from MONDO/OMIM cross-reference during database integration (e.g., via MONDO registry). (no direct evidence in retrieved texts)

1.3 Synonyms / alternative names

• Aspartoacylase deficiency (rossler2023canavan’sspongiformleukodystrophy pages 1-4)
• Spongy degeneration of the CNS / spongiform leukodystrophy (rossler2023canavan’sspongiformleukodystrophy pages 1-4, matalon2002canavandiseaseprenatal pages 1-3)
• N-acetylaspartic aciduria (sass2019aspartoacylasedeficiency(canavan pages 4-6)
• Van Bogaert–Bertrand disease (janson2002clinicalprotocol.gene pages 1-2)

1.4 Evidence provenance (patient-level vs aggregated resources)

Evidence in this report is derived from a mix of (i) aggregated cohort natural history (23 cases plus literature comparison), (ii) individual case report/review, (iii) mechanistic review synthesizing multiple experimental studies, (iv) interventional trial protocols and expanded-access records, and (v) animal-model pathology studies. (bley2021thenaturalhistory pages 1-2, rossler2023canavan’sspongiformleukodystrophy pages 1-4, grønbækthygesen2024cellularandmolecular pages 1-2, NCT04998396 chunk 1, takeda2024myelinlesionin pages 1-2)

2. Etiology

2.1 Disease causal factors

Genetic cause (primary): Autosomal recessive biallelic pathogenic variants in ASPA leading to aspartoacylase deficiency, impaired NAA hydrolysis, and NAA accumulation in CNS. (matalon2002canavandiseaseprenatal pages 14-16, bley2021thenaturalhistory pages 1-2)

Mechanistic cause: ASPA normally hydrolyzes NAA to acetate and aspartate; ASPA deficiency leads to NAA accumulation and white matter pathology. (corti2023adenoassociatedvirusmediatedgene pages 1-2, grønbækthygesen2024cellularandmolecular pages 1-2)

2.2 Risk factors

• Genetic risk factor: Being a carrier of an ASPA pathogenic variant; disease occurs in children with biallelic variants. (matalon2002canavandiseaseprenatal pages 14-16)
• Population risk: Elevated carrier frequency estimates reported for Ashkenazi Jewish populations (range ~1/40 to 1/82). (matalon2002canavandiseaseprenatal pages 14-16)

2.3 Protective factors

No validated protective genetic or environmental factors were identified in the retrieved sources. (no direct evidence)

2.4 Gene–environment interactions

Recent mechanistic synthesis emphasizes that phenotype is a spectrum influenced by “genetic and environmental factors,” but specific gene–environment interaction mechanisms were not defined in the retrieved sources. (grønbækthygesen2024cellularandmolecular pages 7-8)

3. Phenotypes

3.1 Core clinical phenotypes (human)

Typical age of onset: “Onset of symptoms was between 0 and 6 months.” (bley2021thenaturalhistory pages 1-2)

Early hallmark phenotypes: Severe psychomotor disability and macrocephaly emerging in infancy (“Macrocephaly became apparent between 4 and 18 months of age”). (bley2021thenaturalhistory pages 1-2)

Common early manifestations (frequency from cohort): Within first 6 months, developmental delay (17/23), macrocephaly (12/23), abnormal eye movements (12/23). (bley2021thenaturalhistory pages 1-2)

Seizures: Rare in the first year but “increase in frequency over time,” with highest frequency toward end of first decade. (bley2021thenaturalhistory pages 1-2, bley2021thenaturalhistory pages 6-7)

Imaging-associated clinical trajectory: Progressive disease with early white matter edema/vacuolation that can progress toward atrophy/ventriculomegaly in later phases. (rossler2023canavan’sspongiformleukodystrophy pages 4-6)

3.2 Suggested HPO terms (examples; non-exhaustive)

• Developmental delay — HP:0001263
• Hypotonia — HP:0001252
• Macrocephaly — HP:0000256
• Abnormal eye movements / nystagmus — HP:0000639
• Seizures — HP:0001250
• Spasticity — HP:0001257
• Leukodystrophy / abnormal white matter — HP:0002415

(bley2021thenaturalhistory pages 1-2, rossler2023canavan’sspongiformleukodystrophy pages 1-4, corti2023adenoassociatedvirusmediatedgene pages 1-2)

3.3 Quality-of-life impact

Formal QoL instruments (EQ-5D/SF-36/PROMIS) were not reported in the retrieved sources. Functional impact is substantial, with severe psychomotor disability and limited milestone acquisition. (bley2021thenaturalhistory pages 1-2, matalon2002canavandiseaseprenatal pages 1-3)

4. Genetic / molecular information

4.1 Causal gene

• ASPA (aspartoacylase). Loss of ASPA activity causes Canavan disease. (matalon2002canavandiseaseprenatal pages 14-16, grønbækthygesen2024cellularandmolecular pages 1-2)

4.2 Pathogenic variant classes and molecular consequences

• Loss-of-function is the dominant mechanism at the gene level. (matalon2002canavandiseaseprenatal pages 14-16)
• A major contemporary concept is that many missense ASPA variants cause disease by protein destabilization → misfolding → protein quality control/proteasomal degradation, leading to reduced cellular abundance and functional enzyme loss. (grønbækthygesen2024cellularandmolecular pages 1-2, grønbækthygesen2024cellularandmolecular pages 21-22)

Direct abstract/review quotes supporting this concept: * The 2024 review states data “effectively categorize CD as a protein misfold- ing disorder (proteinopathy).” (grønbækthygesen2024cellularandmolecular pages 22-24)

4.3 Genotype–phenotype considerations / “mild” alleles

CD phenotypes are “better described as a spectrum of severity.” (grønbækthygesen2024cellularandmolecular pages 7-8)

The 2024 review notes candidate variants associated with milder presentations (reflecting residual activity/partial function), including R71H and Y288C among others. (grønbækthygesen2024cellularandmolecular pages 8-9)

4.4 Allele frequencies / population data

Carrier frequency in Ashkenazi Jewish populations has been estimated in the range ~1/40–1/82 (estimates vary by study and time). (matalon2002canavandiseaseprenatal pages 14-16)

4.5 Modifier genes / epigenetics

The natural history study observed that phenotype concordance among siblings but variability among individuals with identical mutations suggests unknown modifiers. (bley2021thenaturalhistory pages 1-2)

No specific modifier genes or epigenetic signatures were identified in the retrieved sources. (no direct evidence)

5. Environmental information

No established non-genetic environmental or lifestyle causal contributors were identified in the retrieved sources; CD is primarily a Mendelian metabolic leukodystrophy driven by ASPA deficiency. (matalon2002canavandiseaseprenatal pages 14-16, bley2021thenaturalhistory pages 1-2)

6. Mechanism / pathophysiology

6.1 Core causal chain (molecular → cellular → tissue → clinical)

1. Trigger: Biallelic ASPA loss-of-function variants cause reduced/absent ASPA enzyme activity. (matalon2002canavandiseaseprenatal pages 14-16)
2. Biochemical consequence: Failure to hydrolyze NAA → acetate + aspartate, causing NAA accumulation. (grønbækthygesen2024cellularandmolecular pages 1-2, corti2023adenoassociatedvirusmediatedgene pages 1-2)
3. Cellular/tissue consequence: Oligodendrocyte dysfunction, hypomyelination/dysmyelination, and spongiform white-matter vacuolation. (corti2023adenoassociatedvirusmediatedgene pages 1-2, bley2021thenaturalhistory pages 1-2)
4. Clinical consequence: Early-infantile onset progressive neurologic impairment, macrocephaly, psychomotor disability, and later seizures/spasticity. (bley2021thenaturalhistory pages 1-2, corti2023adenoassociatedvirusmediatedgene pages 1-2)

6.2 Pathway schematic (recent visual evidence)

A 2024 review figure provides a neuron–oligodendrocyte schematic of the NAA cycle and how ASPA deficiency disrupts NAA catabolism in Canavan disease. (grønbækthygesen2024cellularandmolecular media eaa25b8f)

6.3 Molecular mechanism of many missense variants (2024 concept)

The 2024 mechanistic review synthesizes high-throughput and computational evidence that many pathogenic ASPA variants reduce protein stability and abundance (fold destabilization), linking CD to proteostasis/PQC mechanisms and motivating potential small-molecule stabilizers or degradation blockers. (grønbækthygesen2024cellularandmolecular pages 21-22, grønbækthygesen2024cellularandmolecular pages 22-24)

6.4 Suggested ontology terms

GO biological processes (examples): * N-acetylaspartate metabolic process (supported conceptually by ASPA function) (grønbækthygesen2024cellularandmolecular pages 1-2) * Myelination / CNS myelination (bley2021thenaturalhistory pages 1-2, corti2023adenoassociatedvirusmediatedgene pages 1-2)

Cell types (CL examples): * Oligodendrocyte (central role; oligodendrocyte dysfunction highlighted) (corti2023adenoassociatedvirusmediatedgene pages 1-2, grønbækthygesen2024cellularandmolecular pages 1-2) * Astrocyte (astrocyte activation/gliosis in models) (takeda2024myelinlesionin pages 2-6)

7. Anatomical structures affected

7.1 Primary organs/systems

• Central nervous system white matter (leukodystrophy; spongiform degeneration). (bley2021thenaturalhistory pages 1-2, rossler2023canavan’sspongiformleukodystrophy pages 1-4)

7.2 Imaging-anatomy patterns

MRI typically shows diffuse white matter involvement; the 2023 review notes frequent involvement of basal ganglia/thalami with overall widespread supratentorial and infratentorial white matter changes, and MRS shows an elevated NAA peak. (rossler2023canavan’sspongiformleukodystrophy pages 4-6)

7.3 Suggested UBERON terms (examples)

• Brain white matter
• Cerebral cortex
• Brainstem

(rossler2023canavan’sspongiformleukodystrophy pages 4-6)

8. Temporal development

• Onset: early infancy; often uneventful perinatal period. (bley2021thenaturalhistory pages 1-2)
• Progression: progressive neurodevelopmental stagnation/decline; seizures increase over the first decade. (bley2021thenaturalhistory pages 6-7)
• Critical window for intervention (inferred from early course): early diagnosis in the first 1–2 years is emphasized by natural history timing and by trial eligibility (most gene therapy protocols enroll infants/toddlers). (bley2021thenaturalhistory pages 1-2, NCT04998396 chunk 1, NCT04833907 chunk 1)

9. Inheritance and population

9.1 Inheritance

Autosomal recessive; carriers are asymptomatic. (matalon2002canavandiseaseprenatal pages 12-14)

9.2 Population distribution / founder effects

CD historically associated with Ashkenazi Jewish populations, but more recent cohorts note diagnoses “more frequently outside Ashkenazi Jewish communities than previously reported,” and many new diagnoses occur without known Ashkenazi ancestry. (bley2021thenaturalhistory pages 1-2, matalon2002canavandiseaseprenatal pages 14-16)

9.3 Prevalence/incidence

Quantitative prevalence/incidence estimates were not available in the retrieved evidence corpus (e.g., Orphanet registry data not retrieved). This is a gap for the knowledge base entry. (no direct evidence)

10. Diagnostics

10.1 Core diagnostic biomarkers and tests

Metabolite biomarker: Elevated NAA in urine/blood and/or brain. (bley2021thenaturalhistory pages 1-2)

Neuroimaging: MRI is the principal imaging tool; MR spectroscopy is diagnostically important because it shows a markedly elevated NAA peak. (rossler2023canavan’sspongiformleukodystrophy pages 1-4, rossler2023canavan’sspongiformleukodystrophy pages 4-6)

Genetic testing: Molecular confirmation by ASPA mutation analysis is part of standard diagnosis. (bley2021thenaturalhistory pages 1-2)

Direct quote (diagnostic statement): “CD is diagnosed by detection of elevated NAA in urine or blood or in brain by proton MR spectroscopy [...], as well as by ASPA mutation analysis.” (bley2021thenaturalhistory pages 1-2)

10.2 Screening (carrier/prenatal)

Because the disorder is autosomal recessive, carrier testing and prenatal/preimplantation genetic testing are feasible once familial variants are known. (matalon2002canavandiseaseprenatal pages 14-16, rossler2023canavan’sspongiformleukodystrophy pages 1-4)

11. Outcomes / prognosis

Earlier sources describe reduced survival and progressive disability, with severe early-onset forms often fatal in childhood/adolescence; cohort-level survival statistics are not comprehensively captured in the retrieved recent sources, but reduced life expectancy and progressive course are consistent across clinical descriptions. (matalon2002canavandiseaseprenatal pages 1-3, corti2023adenoassociatedvirusmediatedgene pages 1-2, rossler2023canavan’sspongiformleukodystrophy pages 1-4)

12. Treatment

12.1 Supportive care (standard of care)

No established curative therapy is cited in the retrieved sources; care is described as multidisciplinary and supportive (nutrition/feeding, seizure management, monitoring neurologic complications). (matalon2002canavandiseaseprenatal pages 1-3, matalon2002canavandiseaseprenatal pages 12-14)

MAXO suggestions (examples): * Seizure management * Nutritional support / enteral feeding * Physical therapy / rehabilitation

(matalon2002canavandiseaseprenatal pages 12-14)

12.2 Advanced therapeutics (2023–2024: gene therapy emphasis)

Key concept: Gene replacement is a rational approach because CD is a monogenic enzyme deficiency, and rAAV vectors (notably AAV9 and Olig001) are in active clinical development. (corti2023adenoassociatedvirusmediatedgene pages 1-2, ceravolo2024updateonleukodystrophies pages 8-10)

Real-world implementation (trial operations): Two major programs include a systemic AAV9 approach (BBP-812/CANaspire) and an intracerebroventricular oligodendrocyte-targeting approach (MYR-101/CAN-GT). (NCT04998396 chunk 1, NCT04833907 chunk 1)

Table: This table summarizes the main Canavan disease clinical gene therapy programs and studies identified in the evidence, including vector platform, route, study design, age ranges, and core biomarkers. It is useful for comparing how current and historical programs differ in delivery strategy and outcome measures.

Recent clinical report (2023): A published treated case used dual i.v. + i.c.v. rAAV9-CB6-ASPA with prophylactic immunomodulation; assessments included antibody monitoring, vector genomes by qPCR, imaging (MRI/DTI), and NAA measurements in CSF/brain by mass spectrometry and MRS. (corti2023adenoassociatedvirusmediatedgene pages 1-2)

MAXO suggestions (examples): * Gene therapy (AAV-mediated gene transfer) * Intracerebroventricular administration * Intravenous administration * Immunosuppressive therapy / immune modulation

(NCT04998396 chunk 1, NCT04833907 chunk 1, NCT05317780 chunk 1)

12.3 Expert opinion / analysis (authoritative synthesis)

The 2024 leukodystrophy trials review emphasizes that “gene therapy is emerging as a potential treatment avenue” for leukodystrophies and notes ongoing in vivo AAV ASPA programs for Canavan disease, while acknowledging the need for optimized delivery and adjunct approaches such as immunomodulation. (ceravolo2024updateonleukodystrophies pages 8-10)

13. Prevention

13.1 Primary prevention

Primary prevention is feasible through carrier screening in at-risk populations and family-based testing, given autosomal recessive inheritance and known carrier frequencies in some populations. (matalon2002canavandiseaseprenatal pages 14-16)

13.2 Secondary prevention

Early diagnosis using urine/blood NAA and MRI/MRS may allow earlier supportive interventions and eligibility for clinical trials with age-limited enrollment windows. (bley2021thenaturalhistory pages 1-2, NCT04998396 chunk 1)

13.3 Tertiary prevention

Multidisciplinary supportive care aims to reduce complications (nutrition/aspiration risk, seizure control). (matalon2002canavandiseaseprenatal pages 12-14)

14. Other species / natural disease

The retrieved evidence focuses on engineered rodent models; naturally occurring non-human disease was not identified in the retrieved corpus (outside mention of a naturally occurring “tremor rat” model with a large deletion including ASPA and other genes, complicating attribution). (grønbækthygesen2024cellularandmolecular pages 8-9)

15. Model organisms

15.1 Rat model (2024: Aspa knockout rat)

A TALEN-generated Aspa-knockout rat shows vacuolation with swollen axons, hypomyelination, and astrocyte activation, particularly in brainstem reticular formation and motor pathways, but notably did not show overt neurologic signs in the examined cohorts. (takeda2024myelinlesionin pages 1-2, takeda2024myelinlesionin pages 2-6)

15.2 Mouse and other rodent models (review synthesis)

Multiple Aspa mouse models and a “tremor rat” are described; engineered Aspa−/− mice can show macroencephaly, ataxia/tremor, seizures in some animals, and elevated urine NAA. (grønbækthygesen2024cellularandmolecular pages 8-9)

15.3 Model utility and limitations

• Utility: Reproduces key CNS pathology (vacuolation/spongiform change, hypomyelination) for testing NAA/pathogenesis hypotheses and gene therapy. (takeda2024myelinlesionin pages 2-6, grønbækthygesen2024cellularandmolecular pages 8-9)
• Limitation: Species/model differences in overt clinical phenotypes (e.g., rat model with strong histopathology but minimal early neurologic signs). (takeda2024myelinlesionin pages 1-2)

Key recent developments (prioritizing 2023–2024)

1. Mechanistic reframing (2024): A 2024 ASPA-focused review synthesizes high-throughput and structural evidence indicating many ASPA missense variants act through folding destabilization and PQC-mediated degradation, with the explicit conclusion that data “effectively categorize CD as a protein misfold- ing disorder (proteinopathy).” (grønbækthygesen2024cellularandmolecular pages 22-24, grønbækthygesen2024cellularandmolecular pages 21-22)
2. Clinical translation (2023): A published AAV9-ASPA gene therapy case report details dual-route delivery (i.v.+i.c.v.) and immunomodulation with multimodal biomarker tracking (NAA in CSF/brain, MRI/DTI). (corti2023adenoassociatedvirusmediatedgene pages 1-2)
3. Active trials (2021–present, still current in 2023–2024 landscape): BBP-812 (AAV9, IV) and MYR-101 (Olig001, ICV) are ongoing/active programs with NAA (urine/CSF/brain) and myelination imaging as key pharmacodynamic endpoints. (NCT04998396 chunk 1, NCT04833907 chunk 1)
4. New animal model (2024): A clean Aspa-knockout rat model provides a platform with human-like white-matter vacuolation/hypomyelination for mechanistic and therapeutic studies. (takeda2024myelinlesionin pages 1-2)

URLs and publication dates (selected key sources)

• Grønbæk-Thygesen & Hartmann-Petersen. Cell & Bioscience. Apr 2024. https://doi.org/10.1186/s13578-024-01224-6 (grønbækthygesen2024cellularandmolecular pages 1-2)
• Ceravolo et al. Journal of Neurology. Sep 2024. https://doi.org/10.1007/s00415-023-11996-5 (ceravolo2024updateonleukodystrophies pages 8-10)
• Corti et al. Molecular Therapy – Methods & Clinical Development. Sep 2023. https://doi.org/10.1016/j.omtm.2023.06.001 (corti2023adenoassociatedvirusmediatedgene pages 1-2)
• Rossler et al. Journal of Ultrasound. Feb 2023. https://doi.org/10.1007/s40477-022-00667-2 (rossler2023canavan’sspongiformleukodystrophy pages 1-4)
• Takeda et al. Experimental Animals. Mar 2024. https://doi.org/10.1538/expanim.23-0089 (takeda2024myelinlesionin pages 1-2)
• Bley et al. Orphanet Journal of Rare Diseases. May 2021. https://doi.org/10.1186/s13023-020-01659-3 (bley2021thenaturalhistory pages 1-2)
• ClinicalTrials.gov: NCT04998396 (CANaspire/BBP-812). First posted 2021. https://clinicaltrials.gov/study/NCT04998396 (NCT04998396 chunk 1)
• ClinicalTrials.gov: NCT04833907 (CAN-GT/MYR-101). First posted 2021. https://clinicaltrials.gov/study/NCT04833907 (NCT04833907 chunk 1)

Known gaps (not resolved in retrieved evidence set)

• MONDO ID, ICD-10/ICD-11, MeSH identifiers were not present in the retrieved full-text/records; these should be populated from external ontology registries during integration. (no direct evidence)
• Point prevalence/incidence values were not retrieved from Orphanet/registries in this tool run; should be added from Orphanet/GBD/national registries. (no direct evidence)

References

1. (bley2021thenaturalhistory pages 1-2): Annette Bley, Jonas Denecke, Alfried Kohlschütter, Gerhard Schön, Sandra Hischke, Philipp Guder, Tatjana Bierhals, Heather Lau, Maja Hempel, and Florian S. Eichler. The natural history of canavan disease: 23 new cases and comparison with patients from literature. Orphanet Journal of Rare Diseases, May 2021. URL: https://doi.org/10.1186/s13023-020-01659-3, doi:10.1186/s13023-020-01659-3. This article has 54 citations and is from a peer-reviewed journal.

2. (corti2023adenoassociatedvirusmediatedgene pages 1-2): Manuela Corti, Barry J. Byrne, Dominic J. Gessler, Grace Thompson, Samantha Norman, Jenna Lammers, Kirsten E. Coleman, Cristina Liberati, Melissa E. Elder, Maria L. Escolar, Ibrahim S. Tuna, Clementina Mesaros, Gary I. Kleiner, Deborah S. Barbouth, Heather L. Gray-Edwards, Nathalie Clement, Brian D. Cleaver, and Guangping Gao. Adeno-associated virus-mediated gene therapy in a patient with canavan disease using dual routes of administration and immune modulation. Molecular Therapy - Methods & Clinical Development, 30:303-314, Sep 2023. URL: https://doi.org/10.1016/j.omtm.2023.06.001, doi:10.1016/j.omtm.2023.06.001. This article has 30 citations.

3. (grønbækthygesen2024cellularandmolecular pages 1-2): Martin Grønbæk-Thygesen and Rasmus Hartmann-Petersen. Cellular and molecular mechanisms of aspartoacylase and its role in canavan disease. Cell & Bioscience, Apr 2024. URL: https://doi.org/10.1186/s13578-024-01224-6, doi:10.1186/s13578-024-01224-6. This article has 12 citations and is from a peer-reviewed journal.

4. (matalon2002canavandiseaseprenatal pages 14-16): Reuben Matalon and Kimberlee Michals Matalon. Canavan disease prenatal diagnosis and genetic counseling. Obstetrics and gynecology clinics of North America, 29 2:297-304, Jun 2002. URL: https://doi.org/10.1016/s0889-8545(01)00003-1, doi:10.1016/s0889-8545(01)00003-1. This article has 28 citations and is from a peer-reviewed journal.

5. (NCT04998396 chunk 1): A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial). Aspa Therapeutics. 2021. ClinicalTrials.gov Identifier: NCT04998396

6. (NCT04833907 chunk 1): rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease. Myrtelle Inc.. 2021. ClinicalTrials.gov Identifier: NCT04833907

7. (rossler2023canavan’sspongiformleukodystrophy pages 1-4): Leon Rossler, Stefan Lemburg, Almut Weitkämper, Charlotte Thiels, Sabine Hoffjan, Huu Phuc Nguyen, Thomas Lücke, and Christoph M. Heyer. Canavan’s spongiform leukodystrophy (aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature. Journal of Ultrasound, 26:757-764, Feb 2023. URL: https://doi.org/10.1007/s40477-022-00667-2, doi:10.1007/s40477-022-00667-2. This article has 11 citations.

8. (matalon2002canavandiseaseprenatal pages 1-3): Reuben Matalon and Kimberlee Michals Matalon. Canavan disease prenatal diagnosis and genetic counseling. Obstetrics and gynecology clinics of North America, 29 2:297-304, Jun 2002. URL: https://doi.org/10.1016/s0889-8545(01)00003-1, doi:10.1016/s0889-8545(01)00003-1. This article has 28 citations and is from a peer-reviewed journal.

9. (sass2019aspartoacylasedeficiency(canavan pages 4-6): Jörn Oliver Sass and Ina Knerr. Aspartoacylase deficiency (canavan disease, n-acetylaspartic aciduria). Human Pathobiochemistry, pages 15-21, Mar 2019. URL: https://doi.org/10.1007/978-981-13-2977-7_2, doi:10.1007/978-981-13-2977-7_2. This article has 1 citations.

10. (janson2002clinicalprotocol.gene pages 1-2): Christopher Janson, Scott McPhee, Larissa Bilaniuk, John Haselgrove, Mark Testaiuti, Andrew Freese, Dah-Jyuu Wang, David Shera, Peter Hurh, Joan Rupin, Elizabeth Saslow, Olga Goldfarb, Michael Goldberg, Ghassem Larijani, William Sharrar, Larisa Liouterman, Angelique Camp, Edwin Kolodny, Jude Samulski, and Paola Leone. Clinical protocol. gene therapy of canavan disease: aav-2 vector for neurosurgical delivery of aspartoacylase gene (aspa) to the human brain. Human gene therapy, 13 11:1391-412, Jul 2002. URL: https://doi.org/10.1089/104303402760128612, doi:10.1089/104303402760128612. This article has 329 citations and is from a peer-reviewed journal.

11. (takeda2024myelinlesionin pages 1-2): Shuji Takeda, Rika Hoshiai, Miyuu Tanaka, Takeshi Izawa, Jyoji Yamate, Takashi Kuramoto, and Mitsuru Kuwamura. Myelin lesion in the aspartoacylase (aspa) knockout rat, an animal model for canavan disease. Experimental Animals, 73:347-356, Mar 2024. URL: https://doi.org/10.1538/expanim.23-0089, doi:10.1538/expanim.23-0089. This article has 0 citations and is from a peer-reviewed journal.

12. (grønbækthygesen2024cellularandmolecular pages 7-8): Martin Grønbæk-Thygesen and Rasmus Hartmann-Petersen. Cellular and molecular mechanisms of aspartoacylase and its role in canavan disease. Cell & Bioscience, Apr 2024. URL: https://doi.org/10.1186/s13578-024-01224-6, doi:10.1186/s13578-024-01224-6. This article has 12 citations and is from a peer-reviewed journal.

13. (bley2021thenaturalhistory pages 6-7): Annette Bley, Jonas Denecke, Alfried Kohlschütter, Gerhard Schön, Sandra Hischke, Philipp Guder, Tatjana Bierhals, Heather Lau, Maja Hempel, and Florian S. Eichler. The natural history of canavan disease: 23 new cases and comparison with patients from literature. Orphanet Journal of Rare Diseases, May 2021. URL: https://doi.org/10.1186/s13023-020-01659-3, doi:10.1186/s13023-020-01659-3. This article has 54 citations and is from a peer-reviewed journal.

14. (rossler2023canavan’sspongiformleukodystrophy pages 4-6): Leon Rossler, Stefan Lemburg, Almut Weitkämper, Charlotte Thiels, Sabine Hoffjan, Huu Phuc Nguyen, Thomas Lücke, and Christoph M. Heyer. Canavan’s spongiform leukodystrophy (aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature. Journal of Ultrasound, 26:757-764, Feb 2023. URL: https://doi.org/10.1007/s40477-022-00667-2, doi:10.1007/s40477-022-00667-2. This article has 11 citations.

15. (grønbækthygesen2024cellularandmolecular pages 21-22): Martin Grønbæk-Thygesen and Rasmus Hartmann-Petersen. Cellular and molecular mechanisms of aspartoacylase and its role in canavan disease. Cell & Bioscience, Apr 2024. URL: https://doi.org/10.1186/s13578-024-01224-6, doi:10.1186/s13578-024-01224-6. This article has 12 citations and is from a peer-reviewed journal.

16. (grønbækthygesen2024cellularandmolecular pages 22-24): Martin Grønbæk-Thygesen and Rasmus Hartmann-Petersen. Cellular and molecular mechanisms of aspartoacylase and its role in canavan disease. Cell & Bioscience, Apr 2024. URL: https://doi.org/10.1186/s13578-024-01224-6, doi:10.1186/s13578-024-01224-6. This article has 12 citations and is from a peer-reviewed journal.

17. (grønbækthygesen2024cellularandmolecular pages 8-9): Martin Grønbæk-Thygesen and Rasmus Hartmann-Petersen. Cellular and molecular mechanisms of aspartoacylase and its role in canavan disease. Cell & Bioscience, Apr 2024. URL: https://doi.org/10.1186/s13578-024-01224-6, doi:10.1186/s13578-024-01224-6. This article has 12 citations and is from a peer-reviewed journal.

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22. (NCT05317780 chunk 1): Canavan-Single Patient IND. University of Florida. ClinicalTrials.gov Identifier: NCT05317780