Transfidelity for Protein Stability

FIDEL

Neurosciences

Neurodegenerative diseases such as Alzheimer's Disease are devastating conditions that impact millions globally. These diseases are driven by the misfolding and aggregation of proteins, which lead to brain cell death and cognitive decline. To make matters worse, as we age our cells become more error-prone, resulting in more errors during protein printing, causing proteins to clump together and form aggregates. Project Transfidelity aims to solve this by improving the accuracy of protein printing, preventing toxic aggregates from forming. Led by Dr. Dimitri Scherbakov and Dr. Rashid Akbergenov, with over 50 years of combined experience in the lab, we have identified two molecules that may improve the efficiency of protein production, potentially preventing protein aggregates, hypothesized to cause dementia. Despite the significant research funding allocated to neurodegenerative diseases, current therapies continue to treat the symptoms caused by the protein aggregates, with little progress made to stop or reverse disease. We’re trying to go after a potential root cause - rather than trying to clear aggregates once they are there, we aim to prevent them from forming in the first place by reducing the production of faulty proteins. With a clear path towards developing novel intellectual property (IP) and an ever-growing target market, we believe we are poised to make an impact on neurodegenerative disorders and the way we age.

Owned by

0x907Bb…35680

Contract:

0x23121…BbE1e

Description

Project Transfidelity aims to solve this by improving the accuracy of protein printing, preventing toxic aggregates from forming. Led by Dr. Dimitri Scherbakov and Dr. Rashid Akbergenov, with over 50 years of combined experience in the lab, we have identified two molecules that may improve the efficiency of protein production, potentially preventing protein aggregates, hypothesized to cause dementia.

Despite the significant research funding allocated to neurodegenerative diseases, current therapies continue to treat the symptoms caused by the protein aggregates, with little progress made to stop or reverse disease. We’re trying to go after a potential root cause - rather than trying to clear aggregates once they are there, we aim to prevent them from forming in the first place by reducing the production of faulty proteins. With a clear path towards developing novel intellectual property (IP) and an ever-growing target market, we believe we are poised to make an impact on neurodegenerative disorders and the way we age.

Team

0xa1bb8…1791c

Owner

Organisation

University of Basel

Experiment Cost

$242,540.00

Project Score

Technology Readiness Level

PRE-TRL

TRL 1

TRL 2

Price of FIDEL

$0.00187

Project Progress

All updates

All categories

Timeline

Activity

Time	Type	$FIDEL	USD	ETH	From

Transfidelity for Protein Stability

FIDEL

Neurosciences

Owned by

0x907Bb…35680

Contract:

0x23121…BbE1e

Description

Team

0xa1bb8…1791c

Owner

Organisation

University of Basel

Experiment Cost

$242,540.00

Project Score

Technology Readiness Level

PRE-TRL

TRL 1

TRL 2

Price of FIDEL

$0.00187

Project Progress

All updates

All categories

Timeline

Activity

Time	Type	$FIDEL	USD	ETH	From

Rationale

The project has conducted substantial in vitro experimental work, including dual-reporter assays, polysome profiling, aggregation assays, and cell-based toxicity assessments in HEK293 cells, clearly advancing it beyond TRL 1 (pure concept). However, all experiments have been performed in standard immortalized cell lines (HEK293) using reporter constructs rather than disease-relevant models. No experiments have been conducted in disease-relevant systems such as iPSC-derived neurons, patient-derived organoids, or in vivo animal models—the iPSC-derived Parkinson's neuronal model is under development but not yet completed, and compound validation in that model is planned for early 2026. This firmly places the project at TRL 2.

Assessment

Low Confidence

RecommendationSUPPLEMENT

Total Score3.60

Overall Assessment

The Transfidelity project achieves a final weighted score of 3.60 out of 5.00, indicating solid performance for a TRL 2 project with notable strengths and identifiable gaps. The project's strongest dimension is therapeutic relevance (score 4, weighted 1.80), driven by a scientifically compelling and novel mechanism of action—enhancing ribosomal translation fidelity to prevent protein misfolding upstream—supported by statistically significant early experimental results and published literature. The safety profile is also encouraging (score 4, weighted 0.60), with no toxicity observed and the critical demonstration that protein synthesis rates are maintained. The utility of candidates (score 3, weighted 0.60) and intellectual property position (score 3, weighted 0.45) are at moderate levels appropriate for this stage: two hit compounds have been identified and chemically evaluated, and the first-in-class positioning is strong, but hit-to-lead optimization and IP formalization are still pending. Therapeutic optionality (score 3, weighted 0.15) shows promise given the broad mechanism but lacks experimental validation beyond the primary indication. Key risks and gaps include: (1) all efficacy data is from HEK293 cells with reporter constructs—disease-relevant iPSC neuronal validation is the critical upcoming milestone; (2) no disclosed IP filing strategy despite having patentable assets; (3) candidates remain at hit stage without optimization. The project is executing ahead of schedule with a credible team (University of Zurich/Basel) and adequate funding ($254K), positioning it well for the planned December 2025 and early 2026 milestones that will be pivotal for advancing the score across multiple criteria.

Weighted Score

Therapeutic Relevance

Early experimental results strongly support the hypothesis. Two hit compounds demonstrate statistically significant reductions in translational errors in HEK293 cells, with maintained protein synthesis rates (polysome profiling) and reduced aggregation of reporter proteins. The biological relevance is reinforced by published literature linking enhanced translational fidelity to lifespan extension and reduced protein aggregation (e.g., RPS23 K60R studies). The mechanism—preventing misfolded proteins upstream at the ribosome rather than clearing aggregates downstream—is scientifically compelling and addresses a root cause of neurodegeneration. However, all results are in HEK293 cells (a non-neuronal model), and disease-relevant iPSC neuronal validation is still planned, not yet executed. This keeps the score at 4 rather than 5.

Therapeutic Optionality

There are emerging findings suggesting alternative applications. The project explicitly targets multiple neurodegenerative diseases (Alzheimer's, Parkinson's, and related conditions), and the proprietary dual-reporter assay platform is noted as potentially extensible to other proteostasis disorders and broader drug discovery applications. However, these alternative pathways remain conceptual—no concrete experimental data has been generated to validate applications beyond the primary alpha-synuclein/Parkinson's focus. The translational fidelity mechanism is inherently broad (affecting all protein synthesis), which is promising for optionality but also unproven in alternative indications. Score of 3 reflects moderate emerging optionality without substantive validation.

Intellectual Property

The project has several IP-strengthening elements: proprietary dual-reporter assays (stop-codon readthrough and amino acid misincorporation), two identified hit compounds with chemical evaluation completed, and a novel mechanism with no competing translational fidelity modulators in clinical development (first-in-class positioning). These early results could meaningfully strengthen IP filings. However, the project data provides no information on whether patent applications have been filed or formalized, and the compounds are still at the hit stage (not yet optimized leads), which limits the specificity and defensibility of composition-of-matter claims. The absence of any stated IP strategy or filing status is a notable gap at this stage.

Utility Of Candidates

Two potential drug candidates have clearly emerged from screening, and they show promising characteristics: statistically significant reduction in translational errors, maintained protein synthesis rates, reduced aggregation of reporter proteins, and no cellular toxicity in HEK293 cells. Chemical evaluation and red-flag analysis have been completed, which is encouraging for viability. However, the candidates are still at the 'hit' stage—hit-to-lead optimization is planned but not yet initiated. Therapeutic effects have only been demonstrated with reporter constructs (GFP, luciferase) in a non-disease-relevant cell line, not with endogenous disease-relevant proteins (e.g., alpha-synuclein) in neuronal models. The viability of achieving actual therapeutic effects in disease-relevant contexts remains unproven, warranting a score of 3.

Prospects For Safety

Early safety signals are encouraging. The compounds demonstrate improved proteostasis without cellular toxicity in HEK293 cells, and critically, they maintain overall protein synthesis rates while reducing errors—a balance that previous approaches failed to achieve. The red-flag analysis has been completed on both hit compounds, suggesting proactive safety evaluation. The mechanism of enhancing fidelity (rather than inhibiting a pathway) is conceptually lower-risk. However, safety data is limited to a single non-neuronal cell line, and no in vivo toxicity data exists. The impact on neuronal cells, potential off-target effects on normal translation, and long-term safety profiles are entirely unknown. Score of 4 reflects strong early safety indicators with the caveat that much broader safety characterization is needed.