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Aptamers for the early detection and monitoring of neurodegenerative diseases

A novel approach for ALS and FTD using single-stranded RNA aptamers to selectively identify TDP-43 protein aggregates

A new detection method for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) using single-stranded RNA aptamers to selectively detect TDP-43 protein aggregates.


  • Early detection
  • Disease monitoring
  • Histological staining
  • Microscopy

Development Status

  • Undergoing validation

IP Status

  • Priority patent application 2022 (PCT/EP2023/062203)

Commercial Offerings

  • Licensing or co-development/collaborative research


ALS is a highly debilitating and fatal neurodegenerative disease affecting motor neurons, leading to the loss of voluntary limb function, and breathing and swallowing problems. Early detection of ALS neurodegeneration can provide a chance for an early treatment to delay further progression of the disease.

Currently, there are no approved diagnostic tests available for ALS and the disease often goes undetected until late-stage symptom onset. For diagnosed ALS patients, disease progression tracking mainly involves subjective patient self-assessment and the use of muscle strength tests. While the muscle strength test is a quantitative measurement, it can only be used in very late-stage disease progression.

Edinburgh’s technology has the potential to increase the possibility of early detection, diagnosis and intervention by helping to identify and follow treatment effectiveness in clinical trial participants. The technology has been shown to detect TDP-43 aggregates of different sizes, indicating its potential to be used in disease progression tracking as well as early detection of ALS.


TDP-43 is known to accumulate in non-central nervous system tissues prior to symptom onset in neurodegenerative diseases such as ALS and FTD. A common pathological feature observed is the depletion of TDP-43 in the cell nucleus and the accumulation of TDP-43 in the cytoplasm of affected neurons. These toxic aggregates will gradually increase in size and have been proposed to be an early indication of the disease.

The TDP-43 RNA aptamers are capable of binding to and detecting TDP-43 aggregates of different sizes, allowing the identification and quantification of all TDP-43 aggregate species, from the smallest oligomers (20 nm) to the largest aggregates (1-2 micrometres). These aptamers show the potential to be used as molecular probes for the early detection of TDP-43 protein aggregates and the subsequent diagnosis of TDP-43-related neurodegenerative diseases, such as ALS and FTD.


  • Able to detect small and different sizes of TDP-43 aggregates species, showing strong potential for application in early diagnosis and disease progression tracking
  • High affinity and selectivity towards TDP-43 aggregates, less off-target binding than antibodies
  • Offers cost-effective and easier synthesis processes than antibodies
  • Applicable to standard histological staining, standard light microscopy, and super-resolution microscopy, giving a wider range of end users easier access to the technology
  • Improved tissue penetration, cellular uptake and thermostability compared with the use of antibodies or other prior art aptamers due to shorter sequences


Zacco, E et al. Probing TDP-43 condensation using an in silico-designed aptamer. Nat. Commun. 13(1):3306. doi: 10.1038/s41467-022-30944-x (2022).

Please note, the header image is purely illustrative.

Quote: TEC1104423

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Dr Nessim Kichik

Senior Technology Transfer Executive
College of Science and Engineering
College of Medicine and Veterinary Medicine