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ORPHA:100070

Progressive non-fluent aphasia

high confidenceDisorder

Also known as: Agramatic variant of PPA · Agramatic variant of primary progressive aphasia · Non-fluent variant PPA

Publications

1,189

85.2th percentile

Trials

6

Interventional, condition-specific

Researchers

1,267

Distinct authors in sample

Gene link

—

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

non-fluent aphasia (PNFA) is a form of frontotemporal dementia (FTD), characterized by agrammatism, laborious speech, alexia, and agraphia, frequently accompanied by apraxia of speech (AOS). Language comprehension is relatively preserved.

How rare: 1-9 / 100 000 — about one to nine people per hundred thousand.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (2)

Primary Progressive Nonfluent aphasia · non-fluent variant PPA

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.”

4/6 stages with a signal

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

  1. Gene identifiedNot found

    No GenCC disease–gene assertion in this build

  2. LiteraturePresent

    1,189 matched papers (634 in last 10 years) Source

  3. Phenotype characterisedPresent

    60 HPO annotations (e.g. Frontotemporal dementia; Aphasia; Deficit in grammar) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationPartial

    1 EMA designation (none yet with FDA orphan-indication approval) — e.g. Methylthioninium Source

  6. Interventional trialPresent

    6 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?

Not yet — the cause hasn't been pinned down in GenCC.

No strong gene–disease assertion joined for this Orphanet entity.

Phenotypes (Monarch / HPO)

60

Associated phenotypes · MONDO:0015059

  • Frontotemporal dementia
  • Aphasia
  • Deficit in grammar
  • Depression
  • Alexia

Showing 5 of 60 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

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)

1

Designation · no FDA orphan-indication approval yet

  • EMA Methylthioniniumtreatment of progressive non-fluent aphasia · 26/11/2010 · PositiveEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

1,189

1,189 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

1,189 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).

634 in the last 10 years · high confidence · 85.2th percentile (publications denominator)

Phrase hits: 1,189 · MeSH hits: 7

Open Europe PMC search

Who's working on it?

1,267

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
    Piguet O16 papers · 2026

    The University of Sydney, School of Psychology, Sydney, Australia; The University of Sydney, Brain and Mind Centre, Sydney, Australia.

    Papers in Europe PMC
  2. 02
    Ahmed RM10 papers · 2026

    The University of Sydney, Brain and Mind Centre, Sydney, Australia; Royal Prince Alfred Hospital, Sydney, Australia.

    Papers in Europe PMC
  3. 03
    Hodges JR8 papers · 2021

    The University of Sydney, Brain and Mind Centre, Sydney, Australia.

    Papers in Europe PMC
  4. 04
    Burrell JR7 papers · 2025

    Prince of Wales Medical Research Institute, University of New South Wales, Sydney, Australia.

    Papers in Europe PMC
  5. 05
    Irish M7 papers · 2026

    The University of Sydney, School of Psychology, Sydney, Australia; The University of Sydney, Brain and Mind Centre, Sydney, Australia. Electronic address: muireann.irish@sydney.edu.au.

    Papers in Europe PMC
  6. 06
    Foxe D6 papers · 2025

    Brain and Mind Centre, The University of Sydney, Sydney, NSW 2050, Australia.

    Papers in Europe PMC
  7. 07
    Warren JD6 papers · 2025

    Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.

    Papers in Europe PMC
  8. 08
    Kumfor F5 papers · 2025

    The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia; The University of Sydney, School of Psychology, Sydney, NSW, Australia. Electronic address: fiona.kumfor@sydney.edu.au.

    Papers in Europe PMC
  9. 09
    Rohrer JD5 papers · 2025

    Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.

    Papers in Europe PMC
  10. 10
    Thompson JC5 papers · 2025

    Manchester Academic Health Sciences Centre, Cerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Salford, Manchester, UK; Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

6

interventional trials for this specific condition

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

Data as of 11 September 2026

6 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 90.1th percentile).

high confidence · 90.1th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

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

Observational and natural-history studies

1 observational study matches 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 Progressive non-fluent aphasia — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

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.

"Progressive non-fluent aphasia" OR "Agramatic variant of PPA" OR "Agramatic variant of the PPA" OR "Agramatic variant of primary progressive aphasia" OR "Agramatic variant of the primary progressive aphasia" OR "Non-fluent variant PPA" OR "Primary Progressive Nonfluent aphasia"

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Primary Progressive Nonfluent Aphasia

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

"Progressive non-fluent aphasia" OR "Agramatic variant of PPA" OR "Agramatic variant of the PPA" OR "Agramatic variant of primary progressive aphasia" OR "Agramatic variant of the primary progressive aphasia" OR "Non-fluent variant PPA" OR "Primary Progressive Nonfluent aphasia"

Interventional trials matched via: both, 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: 6 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

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

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-27T06:59:38.767Z