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ORPHA:228349

CLN2 disease

low confidenceDisorder

Also known as: NCL2 · Neuronal ceroid lipofuscinosis type 2

Publications

7,911

Trials

5

Interventional, condition-specific

Researchers

1,244

Distinct authors in sample

Gene link

TPP1

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

A rare neuronal ceroid lipofuscinosis characterized by neurodevelopmental delay, impaired motor and language skills, dementia, visual deterioration, extrapyramidal signs, gait dysfunction, and brain atrophy. It may present rarely with (2-18 months), classically late (2-4 years) and juvenile-onset (6-10 years). -onset and late -onset patients are reported to have rapid disease progression leading to complete loss of motor function within 6 years and may be fatal, whereas juvenile onset patients were reported to have milder clinical features including mild learning disability, behavior abnormalities associated with dementia and cognitive function regression. Extrapyramidal, cerebellar signs, retinal degeneration and vision loss may be observed later in the adulthood. This form is most frequently observed in Southern Europe.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (5)

CLN2 · TPP1 neuronal ceroid lipofuscinosis · ceroid lipofuscinosis, neuronal, type 2 · neuronal ceroid lipofuscinosis caused by mutation in TPP1 · neuronal ceroid lipofuscinosis type 2

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

6/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — TPP1

  2. LiteraturePresent

    7,911 matched papers (4,270 in last 10 years) Source

  3. Phenotype characterisedPresent

    15 HPO annotations (e.g. Reduced tissue tripeptidyl peptidase 1 activity; Abnormal nervous system electrophysiology; Increased neuronal autofluorescent lipopigment) Source

  4. Animal modelPresent

    5 genotype models (Mus musculus, Danio rerio) Source

  5. Orphan designationPartial

    1 FDA · 1 EMA designations (none yet with FDA orphan-indication approval) — e.g. recombinant human tripeptidyl-peptidase 1 Source

  6. Interventional trialPresent

    5 matched on ClinicalTrials.gov (1 recruiting in sample)

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (TPP1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

15

Associated phenotypes · MONDO:0008769

  • Reduced tissue tripeptidyl peptidase 1 activity
  • Abnormal nervous system electrophysiology
  • Increased neuronal autofluorescent lipopigment
  • Cerebral atrophy
  • Delayed speech and language development

Showing 5 of 15 — open Monarch for the full list.

Animal models (Monarch / Alliance)

5

Model associations linked to this Mondo ID

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

2

Designations · no FDA orphan-indication approval yet

  • EMA recombinant human tripeptidyl-peptidase 1 (Brineura)Treatment of neuronal ceroid lipofuscinosis type 2 · 12/03/2013 · PositiveEMA designation
  • FDA cerliponase alfa (Brineura)Neuronal Ceroid Lipofuscinosis Type 2 · 2013-04-01

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

1

Drugs / clinical candidates · MONDO_0008769

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

7,911

7,911 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

7,911 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

4,270 in the last 10 years · low confidence

Phrase hits: 514 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,244

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Schulz A25 papers · 2026

    Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

    Papers in Europe PMC
  2. 02
    Nickel M16 papers · 2026

    Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

    Papers in Europe PMC
  3. 03
    Gissen P15 papers · 2026

    UCL Great Ormond Street Institute of Child Health, University College London, London, UK.

    Papers in Europe PMC
  4. 04
    Cooper JD14 papers · 2026

    Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA. cooperjd@wustl.edu.

    Papers in Europe PMC
  5. 05
    Specchio N14 papers · 2024

    Ospedale Pediatrico Bambino Gesù, Rome, Italy.

    Papers in Europe PMC
  6. 06
    Sands MS10 papers · 2026

    Department of Medicine, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.

    Papers in Europe PMC
  7. 07
    Takahashi K9 papers · 2026

    Department of Pediatrics.

    Papers in Europe PMC
  8. 08
    de Los Reyes E8 papers · 2025

    From the Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (A.S., A.K.); BioMarin Pharmaceutical, Novato, CA (T.A., H.C., P.S., D.J.); the Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome (N.S.); Nationwide Children's Hospital and Ohio State University, Columbus (E.L.R.); UCL Great Ormond Street Institute of Child Health, London (P.G.); and the Citigroup Biomedical Imaging Center, Departments of Radiology and Genetic Medicine, Weill Cornell Medical College, New York (D.B., J.P.D.).

    Papers in Europe PMC
  9. 09
    Eultgen EM8 papers · 2026

    Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.

    Papers in Europe PMC
  10. 10
    Mole SE8 papers · 2026

    Medical Research Council Laboratory for Molecular Cell Biology and UCL Great Ormond Street Institute of Child Health, University College London, London, UK. Electronic address: s.mole@ucl.ac.uk.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

5

interventional trials for this specific condition

5 interventional trials matched this specific condition name; 1 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

5 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 89.2th percentile).

low confidence · 89.2th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

5 interventional trials matched after quoted-phrase search and title/condition post-filter.

Observational and natural-history studies

5 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 1 · after dedupe 1 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 1 · dropped 0 · fetched 2026-07-30

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Uncertain / not reviewed (1)

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for CLN2 disease — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Neuronal ceroid lipofuscinosis as a category (Group 3), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 3 — high-cost / lifelong therapy with careful selection

Up to ₹50 lakh per patient

Financial support at notified Centres of Excellence is the figure commonly cited in recent MoHFW/PIB statements. Many Group 3 patients also use the MoHFW voluntary-contribution / crowdfunding portal.

Eligibility and patient selection rules change. Verify with a CoE; the crowdfunding portal is a separate mechanism from CoE funding. Verify

Centres of Excellence (15)
  • All India Institute of Medical Sciences (AIIMS) — New Delhi, Delhi
  • Maulana Azad Medical College — New Delhi, Delhi
  • Sanjay Gandhi Post Graduate Institute of Medical Sciences — Lucknow, Uttar Pradesh
  • Post Graduate Institute of Medical Education and Research (PGIMER) — Chandigarh, Chandigarh
  • Centre for DNA Fingerprinting & Diagnostics with Nizam’s Institute of Medical Sciences — Hyderabad, Telangana
  • King Edward Memorial Hospital — Mumbai, Maharashtra
  • Institute of Post-Graduate Medical Education and Research (IPGMER) — Kolkata, West Bengal
  • Centre for Human Genetics with Indira Gandhi Hospital — Bengaluru, Karnataka
  • Institute of Child Health and Hospital for Children (ICH & HC) — Chennai, Tamil Nadu
  • All India Institute of Medical Sciences (AIIMS) — Jodhpur, Rajasthan
  • Sree Avittam Thirunal Hospital (SAT), Government Medical College — Thiruvananthapuram, Kerala
  • All India Institute of Medical Sciences (AIIMS) — Bhopal, Madhya Pradesh
  • Regional Institute of Medical Sciences (RIMS) — Imphal, Manipur
  • All India Institute of Medical Sciences (AIIMS) — Patna, Bihar
  • Assam Medical College & Hospital — Dibrugarh, Assam

Voluntary contributions / crowdfunding (separate from CoE funding): https://rarediseases.mohfw.gov.in/

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("CLN2 disease" OR "Neuronal ceroid lipofuscinosis type 2" OR "TPP1 neuronal ceroid lipofuscinosis" OR "ceroid lipofuscinosis, neuronal, type 2" OR "neuronal ceroid lipofuscinosis caused by mutation in TPP1") OR ("TPP1" OR "TPP1 syndrome" OR "TPP1-related" OR "CLN2" OR "CLN2 syndrome" OR "CLN2-related")

Run this search on Europe PMC

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"CLN2 disease" OR "Neuronal ceroid lipofuscinosis type 2" OR "TPP1 neuronal ceroid lipofuscinosis" OR "ceroid lipofuscinosis, neuronal, type 2" OR "neuronal ceroid lipofuscinosis caused by mutation in TPP1"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 5 interventional · 5 observational · 1 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase; with hits: phrase

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: NCL2; CLN2

Confidence reasoning

  • Preferred label is short or not clearly distinctive
  • 2 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (7911) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T10:08:00.157Z