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Strategy & Roadmap

child with SDS riding a bike with a winding road in the background to illustrate the Shwachman-Diamond Syndrome Alliance

Collaboration is not enough.

Therapy development needs coordination to achieve results. That's how we drive progress, together.

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Unlike foundations in the past, we understand how rare disease research is most efficiently conducted. Instead of passively soliciting researchers for ideas or funding a favorite without a plan, we invest strategically.

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  • We actively identify projects that are key to SDS therapy development,

  • find the best experts to do the work, and

  • coordinate the efforts to deliver results.

 

We value your donations more than the face value, as we know it's personal. We invest only in critical projects that have the potential to accelerate therapy development and leverage large NIH and other grant funding whenever possible. For example, our mouse project is leveraging substantial NIH funding through the Jackson Laboratory and will provide a critical tool for a wide range of therapy development projects.

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We believe that this strategy is the most effective way to generate results that matter to us, the patient community.

Your support has impact.

See the progress with timelines and costs. 

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Our SDS therapy development roadmap includes a wide range of initiatives and projects driven by us, with your support. We welcome researchers, patient advocates and organizations, and biotech companies to join our efforts toward developing therapies for SDS. This is a living document that we update and refine regularly. Costs and timelines are estimates.

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MOUSE AND OTHER PRECLINICAL MODELS –  IN PROGRESS 

  • Goal: a mouse and/or other models 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.

  • ​Programs/Activities:

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

  • Cost: $300,000
    ($150,000 covered by The Jackson Laboratory/NIH funding)

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iPSC AND OTHER PATIENT DERIVED CELL LINES (BIOBANK) –  IN PROGRESS 

  • Goal: Patient cell lines available to researchers anywhere in the world, to test and develop various SDS therapies.

  • ​Programs/Activities:

    •  LIVE  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: $150,000
    (Leveraging $75,000 covered by Corielle Institute/NIH funding, and a grant from UPenn ODC)

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GLOBAL DATABASE / PATIENT DATA HUB –  IN PROGRESS 

  • Goal: Critical for determining therapeutic endpoints for clinical trials; Global participation and access to data

  • ​Programs/Activities:

    • Survey Platform for patient-reported data and collaboration.

    • 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 knowledgeable physicians, and inclusion of SDS on all relevant panels).

  • Cost: $100,000 per year
    (leveraging grants; $10,000 diagnostics support covered by charity partners)
     

NETWORK DEVELOPMENT AND CLINICAL TRIAL READINESS –  IN PROGRESS  

  • Goal: Facilitating clinical trial planning, initiation, and regulatory agency engagement

  • ​Programs/Activities:

    • Obtaining and promoting ICD-10 (and ICD-11) codes for SDS.

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

      •  DONE  FDA CBER OTAT Patient-Focused Drug Development Listening Meeting

      • Additional meetings are in the planning

    • Continued patient community and research network building

  • Time frame: 2-3 years to build, then ongoing

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

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GENE TARGETED THERAPY DISCOVERY AND DEVELOPMENT –  IN PROGRESS 

  • Goal: Getting pre-clinical work ready for translation into clinical application (therapies for patients)

  • 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)

  • Antisense Oligonucleotide Therapies (ASOs) 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 

  • Goal: Getting pre-clinical work ready for translation into clinical application (therapies for patients)

  • 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)

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NEW TARGET IDENTIFICATION –  PLANNING 

  • Identifying additional downstream targets using proteomics and other -omics

  • 2-4 years

  • $500,000 (leveraging NIH and industry funding)

 
PHASE I (DRUG) CLINICAL TRIAL

  • 1-2 years

  • $1 million (leveraging NIH and industry funding)

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PHASE II (PILOT) CLINICAL TRIAL

  • 1-2 years

  • $5 million (leveraging NIH and industry funding)

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PHASE III CLINICAL TRIAL

  • 3-5 years

  • $10 million (leveraging industry funding)

Why do we need models for SDS?

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Model systems, such as mouse models, are developed to replicate a disease in an organism other than humans. That way, researchers can investigate various aspects of disease without having to burden a human patient. Different research questions need different types of models, from yeast cells to worms to flies to mice and more.​​

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For therapy development, we need a model system that is as close as possible to humans but is practical to work with in order to save time. Mouse models have become the gold standard in research.

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Unfortunately, developing a mouse model for SDS has proven historically difficult, because the gene responsible for most cases of SDS, SBDS, is essential. Mice with too little SBDS are not viable, and mice with some have no SDS symptoms (phenotype). As one of our first major projects, we sat out to try all options to create a mouse model for SDS. This work is still ongoing and we are committed to leaving no stone unturned.

SDS Therapies and Cures Roadmap graphic from model systems to clinical trials in people
Roadmap to Therapies and Cures for SDS
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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​

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