Finances

The SDS Alliance understands how rare disease research is most efficiently conducted.  Instead of passively soliciting researchers for ideas, giving them our hard-earned money, and hoping somehow this exercise will benefit our patient community someday, the SDS Alliance actively identifies projects that are key to therapy development, seeks out the best experts to do the work, and coordinates the efforts to deliver results. The investments we make are highly strategic. The SDS Alliance appreciates how precious your donations are — we will invest only in critical projects that can lead to significant leverage of NIH grant funding and enable additional projects that are essential for therapy development. In fact, our mouse project is already leveraging substantial NIH funding through the Jackson Laboratory. We believe that this strategy will be most effective at generating results that matter to us, the patient community.

SDS Therapies and Cures Roadmap.png
Roadmap to Therapies and Cures for SDS

1. Build humanized mouse and other SDS models

  • that has the most common and relevant human mutation

  • is viable and shows relevant phenotypes

  • designed for testing a wide range of therapeutics
     

2. Characterize the models

  • how does the humanized gene behave in the model

  • what symptoms can be observed (what, when, where)

  • develop measurable biomarkers for testing therapies
     

3. Test and optimize therapies on the model

  • gene editing, base editing, and prime editing therapies

  • antisense oligonucleotide (ASO) and other RNA therapies

  • small molecules and repurposed drugs
     

4. Safety and Efficacy Studies

  • test efficacy and safety of discoveries on suitable models to prepare for clinical trials
     

5. Patient Clinical Trials

  • present results of model work to the FDA and international regulatory agencies to proceed with clinical trials in human patients

  • seek FDA and international approval
     

Goal: SDS Therapies and Cures

​Estimated Timelines and Costs of Projects and Initiatives

 

Our SDS therapy development roadmap includes a wide range of initiatives and projects driven by the SDS Alliance and the research community. We welcome researchers, patient organizations, and biotech companies to join our efforts toward developing therapies for SDS. This is a living document that we update and refine on an ongoing basis.  Costs and timelines are estimates.

MOUSE MODELS –  ACTIVE 
  • Need: a mouse model that reflects the genetics of human SDS and reproduces SDS phenotypes, to enable therapy development based on various strategies, such as gene-targeted approaches, small molecules, and drug repurposing. The initial focus is a mouse model humanized with the splice site mutation and flanking regions.

  • Time frame: 1-2 years for building and initial characterization, 3-4 years for characterization of malignancy predisposition

  • Cost: $250,000
    ($100,000 covered by The Jackson Laboratory/NIH funding).
     

iPSC AND OTHER PATIENT DERIVED CELL LINES (BIOBANK) –  IN PROGRESS ​​
  • Need: Renewable patient cell lines available to researchers anywhere in the world, to test and develop various SDS therapies.

  • Cell line types include Lymphoblastoid Cell Lines (LCLs), fibroblasts, and Induced Pluripotent Stem Cells (iPSCs). De-identified clinical information associated with the samples. Samples are processed, stored, and distributed by the Coriell Institute. Goal of 25-50 patients enrolling, covering various ethnic backgrounds, and the whole range of SDS mutations.

  • Time frame: 2-4 years

  • Cost: $130,000
    ($80,000 covered by Corielle Institute/NIH funding). 

GENE TARGETED THERAPY DISCOVERY AND DEVELOPMENT –  IN PROGRESS 
  • Gene editing, base editing, prime editing. Testing and optimizing lead candidates on mouse model from above. (Drs. Brendel and Baurer at Boston Children's Hospital, USA) 

  • Stop-codon read-through / nonsense suppression (Drs. Cipolli and Bezzerri, Verona, Italy)

  • ASOs (Antisense Oligonucleotide Therapies) and other RNA-based therapies. Discovery, testing, and optimizing of lead candidates on mouse model from above.

  • Time-frame: 3-5 years (from discovery to pre-clinical and proof-of-concept work)

  • $2 million
    (funded in large part by the Principal Investigators (PI) through NIH funding and biopharma industry)
     

DRUG DISCOVERY AND DEVELOPMENT –  IN PROGRESS 
  • Small-molecule screening to find compounds that counteract the ribosome assembly defect in SDS. Test and optimize lead candidates on the mouse model from above. (Dr. Allan Warren, Cambridge, UK) 

  • Drug repurposing (high-throughput screening). Test and optimize lead candidates on the mouse model from above.

  • Time frame: 3-5 years (from discovery to pre-clinical and proof-of-concept work)

  • $2 million
    (funded in large part by the Principal Investigators (PI) through NIH funding and venture capital)

GLOBAL DATABASE / PATIENT DATA HUB –  IN PROGRESS 
  • Need: Critical for determining Therapeutic Endpoints for Trials; Global participation and access to data

  • Genotype/phenotype correlation and identification of new SDS genes and mutations using Whole Exome and Whole Genome Sequencing (WES/WGS)

  • Diagnostics support for patients (through cost assistance, a global network of knowledgable physicians, and inclusion of SDS on all relevant panels).

  • Cost: $100,000 per year
    ($50,000 data collection platform cost covered by RARE-X; $10,000 diagnostics support covered by charity partners)
     

CLINICAL TRIAL READINESS –  PLANNING ​ 
  • Obtaining and promoting ICD-10 (and ICD-11) codes for SDS

  • Engaging with regulatory agencies (i.e. FDA)

  • Continued patient community building

  • Time frame: 2-3 years

  • Cost: $100,000 (likely leveraging PCORI and industry funding)

DOWNSTREAM TARGET IDENTIFICATION
  • Identifying additional downstream targets using proteomics

  • 1-2 years

  • $50,000 (leveraging NIH and industry funding)

 
PHASE I (DRUG) CLINICAL TRIAL
  • 2 years

  • $250,000 (leveraging NIH and industry funding)

PHASE II (PILOT) CLINICAL TRIAL
  • 1.5 years

  • $1.8 million (leveraging NIH and industry funding)

PHASE III CLINICAL TRIAL
  • 3 years

  • $8 million (leveraging industry funding)