Development and Characterization of an NGLY1 Deficiency Disorder Human-on-a-Chip Model

SOURCES SOUGHT NOTICE

1. Sources Sought Number: 75N95019Q00284

2. Title: Development and Characterization of an NGLY1 Deficiency Disorder Human-on-a-Chip Model

3. Classification Code: 99- Miscellaneous

4. NAICS Code: 541714 - Research and Development in Biotechnology (except Nanobiotechnology)

5. Description:
This is a Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential requirement.

This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.

6. Statement of Need and Purpose: The National Center for Advancing Translational Science (NCATS) Therapeutic Development Branch (TDB) program of the National Institutes of Health has a need to to establish in vitro phenotypic models of the NGLY1 deficiency disorder for the TRND NGLY1 Retrophin study. The TDB program requires this service because the program currently does not have the equipment nor the expertise to conduct the experiments at NCATS laboratories.

7. Purpose and Objectives: This acquisition will help to characterize the morphology and physiology of the diseased iPSC motor neurons compared to the wild type iPSC motor neurons, as well as to test each line for neuromuscular junction formation and physiology. This work will be completed using the multi-organ, human-on-a-chip screening platform. This highly customizable model will enable us to use our patient-derived iPSC and create a precise model for a rare disease.

1. Project requirements:

Summary:
Contractor will receive 4 lines of frozen iPSCs, provided by TDB biology, that were derived from patients with a NGLY1 deficiency disorder:
iPSC Lines (To be provided to contractor by NCATS TBD program):
1. Wild Type (WT) Control
2. Isogenic NGLY1 knockout
3. NGLY1 patient 1 sample
4. NGLY1 patient 2 sample

Shipping:
Cells will be shipped to contractor from NCATS via FedEx overnight shipping on dry ice. The program is responsible for sample/package preparation. TDB POC will inform vendor POC via email when cells have been shipped out. Upon receiving iPSCs lines, vendor will inspect vials and make certain cells arrive in proper conditions and will take necessary steps for proper storage of cells until project start date.

Project:
Project will be divided into two main phases followed by statistical analysis with specific steps outlined below:
Milestone 1: Characterize the morphology and physiology of the diseased iPSC-MNs compared to the WT iPSC-MNs:
1. Phase imaging
a. Contractor will look for axonal varicosities (protein agglomeration) using phase contrast microscopy
b. Specific differences in morphology, e.g. axon length and axon branching
2. Immunocytochemistry
a. Contractor will look for axonal varicosities (protein agglomeration) using confocal microscopy
i. Neurofilament or β-III tubulin
ii. Islet-1 (MN specific marker)
b. Specific differences in morphology, e.g. axon length and axon branching
3. Patch-clamp electrophysiology
a. Ion channel currents (Including Na+ and K+)
b. Single firing or repetitive firing action potential waveform

Milestone 2: Test each line for neuromuscular junction formation and physiology:
Determine the effects of NGLY1 deficiency on neuromuscular junction (NMJ) formation, stability and physiology (synchronous muscular contraction at increasing MN stimulation frequencies) in diseased iPSC-MN NMJ systems compared to WT control iPSC-MN NMJ systems.
NMJ system analysis:
1. Test ability to form NMJs by measuring the number of NMJs formed: total number of NMJs in each system.
2. Stability of NMJs: NMJ stability is defined as the ratio of total number of NMJs per system post-stimulation to the number of NMJs pre-stimulation.
3. Synchronous firing of a specific NMJ: One NMJ tested at five different frequencies (0.3, 0.5, 1, 2, and 4 Hz). The percentage of successful muscle contractions driven by electrically-induced MN action potential generation will be quantified.
4. Characteristic morphology of NMJs determined by immunocytochemistry
i. Acetylcholine receptor clustering (alpha-bungarotoxin) and colocalization with MN axons visualized by neurofilament (NF-H) staining
Statistical analysis:
The data generated will be analyzed using a multiple comparison test to determine statistical significance of changes in mutated lines compared to each other for degree of severity as well as to control. Subsequent analytical tests will be run to determine the significance of changes between groups.

Support:
Scientists will be available to consult with TDB scientists throughout the project period. Support will be provided by email, phone, or web meeting per the sponsor preference.

LEVEL OF EFFORT:
• Milestone 1: 2-4 weeks
• Milestone 2: 8-12 weeks
• Statistical Analysis: 1-2 weeks
Data Rights:
All data used and analyzed is sole property of the government. Contractor has no right to any analyzed iPSCs lines provided by TDB
Anticipated period of performance: NCATS expects to issue a purchase order in FY19 (no later than September 30, 2019). The period of performance is estimated to be 120 days ARO.

8. REQUESTED RESPONSE:

The intent of this sources sought notice is to define the procurement strategy (e.g. set-aside, sole source, unrestricted) for a solicitation that NCATS intends to post soon. Interested contractors are requested to respond by (1) identifying how their proposed product meets or exceeds each of the seven salient charactistics listed above, by number; and (2) providing product literature, white papers, or capability statements that demonstrate their bona fide ability to supply such an instrument within the time frame described above.

In addition, please state your business size status and whether you are the manufacturer or authorized distributor of the device you propose.

Please note that NCATS is particularly interested in small business sources. If you are a small business, please state the type of small business (small business; HUBZone; service-disabled, veteran-owned; 8(a); veteran-owned; woman-owned; or small disadvantaged businesses) and your size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible.

Please note that if no responses to this notice are received from either authorized distributors or providers of potentially equivalent items, then this action will be sole-sourced to the provider cited above.

Please provide your DUNS number, organization name, address, point of contact, other information described above, and any other information that may be helpful in developing or finalizing the acquisition requirements.

The information submitted must be must be in an outline format that addresses each of the elements of the project requirement. A cover page and an executive summary may be included but is not required.

The response must include the respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses.

9. All responses to this notice must reference number 75N95019Q00284 and be submitted by email to Jessica Adams, Contract Specialist at jessica.adams@nih.gov.

Responses must be received on or before August 6, 2019, at 5:00pm. Eastern Standard time.

10. Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation.

Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).

.