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Contract Research

Working with Hooke | Capabilities | Models Offered

Hooke Laboratories is a full-service pre-clinical contract research organization (CRO) specializing in rodent models of inflammation and autoimmune diseases. Our motto is "First-class science at competitive prices". We focus on long-term customer relationships, aiming to minimize waste and overhead while generating robust, repeatable results for maximum scientific return from your investment.

Hooke was founded by immunologist Suzana Marusic, MD, PhD in 2007.

Customers come to Hooke not only to run their studies, but also for expertise and advice. Our scientists can help with model selection, study design, and interpretation of results, including investigating the mode of action of your compounds.

All work is performed at our Massachusetts facility, 30 minutes north of Boston/Cambridge (USA). Our customers include leading international pharmas, venture-funded biotechs, universities, and small startups. We’re proud that our focus on efficiency brings us customers from low-cost countries including China, India, and Mexico, while our study quality attracts customers from Kendall Square to California, Europe, and Asia.

Within our specialty, we believe we're the most active and respected CRO in the world.

Working with Hooke

We try to make working with Hooke as comfortable and flexible as working with your own in-house staff. We can do as much, or as little, work as you need.

For customers who need quick turnaround, we can usually start your project within two to four weeks of commitment. We report interim results during your study, so you can make changes or decide on analysis while your study is still running.

Our CRO FAQ outlines how to get started, and answers common questions. Please contact us at or with questions or for a quotation.

Capabilities

This a partial list; if you need an analysis not listed, please contact us at or . Also, see our EAE Analysis Options page.

Models offered

We run all the following models regularly. Each was established at Hooke by a scientist with extensive experience in the relevant research area. We can also work with you - in some cases sharing costs - to develop new or optimized models.

Disease models (in vivo)

Short-term assays and mode of action models

For a quotation, questions, or information about models not listed, contact us at or .

Models and Assays

Listed alphabetically. Click links for additional detail and typical results.

Atopic dermatitis induced by MC903 in C57BL/6 mice

MC903-induced atopic dermatitis (AD) in C57BL/6 mice is an excellent model of human AD (eczema), a chronic inflammatory disease that causes itchy skin lesions.

Model Description
Atopic dermatitis induced by MC903 in C57BL/6 mice Atopic dermatitis is characterized by Th2-dominated skin inflammation and immunoglobulin E (IgE) hypersecretion in both humans and mice.

Collagen-induced arthritis (CIA, rheumatoid arthritis model)

CIA is the most commonly used animal model of human rheumatoid arthritis (RA). The CIA model is usually run in DBA/1 mice, but the disease can also be induced in B10.R111 mice, B10.Q mice, and Lewis rats.

Model Treatment regimen Pros/Cons
Collagen-induced arthritis (CIA) in DBA/1 mice Prophylactic Treatment from immunization. Evaluates efficacy both during and after development of immune response.
Semi-therapeutic Treatment starts when collagen booster is administered. Evaluates effects on B cell expansion, antibody production, and disease development.
Therapeutic Treatment starts at CIA onset. Evaluates efficacy after development of immune response. Least expensive, most stringent.

Cytokine production by innate immune cells

These short term assays evaluate effects of compounds on cytokine production.

Model Description
LPS-induced cytokine production in vivo Mice are injected with E. coli LPS after receiving test compound. Measures TNF, IL-6, and IL-10 serum concentration. Short & inexpensive; good large-scale screen for RA treatments prior to testing in CIA.
Ex vivo whole-blood LPS stimulation Short ex vivo assay, suitable for drug screening.

Delayed-type hypersensitivity (DTH)

Evaluates compound effects on Th17 and Th1 cellular immune responses. Good predictive ability for EAE and CIA. Short.

Model Description
Delayed-type hypersensitivity (DTH) Mice are immunized with mBSA emulsified in CFA, then challenged in footpad with soluble mBSA. Primary readouts are paw swelling and weight vs. PBS negative control. MPO activity and cytokines can be measured as well.

Diabetes in NOD mice

The most commonly used mouse model of type 1 diabetes.

Model Description
Diabetes in NOD mice NOD mice spontaneously develop diabetes, with elevated blood glucose concentration normally detectable at 12 to 30 weeks of age. Primary readouts are blood glucose and histological analysis of pancreata.

Experimental autoimmune encephalomyelitis (EAE, multiple sclerosis model)

EAE is the most commonly used animal model of human multiple sclerosis (MS). Click here for an overview of EAE and a comparison of the models below.

EAE model Duration
(days)		 Description
Adoptive transfer EAE
(in SJL or C57BL/6 mice)		 35 to 40 Sensitive and robust. Can be made Th1 or Th17 dominant. Permits study of cell trafficking (in C57BL/6 mice). Isolates EAE induction phase from effector phase.
Glatiramer acetate (GA)/Copaxone API sameness models 28 Equivalency testing for Teva Copaxone/generic glatiramer acetate per FDA guidance for generic GA sponsors. Hooke routinely performs these assays.
gpMBP69-88/CFA-induced EAE in Lewis rats 16 to 20 Shortest EAE model, used when PK data favors rats.
MOG/CFA-induced EAE in C57BL/6 mice 25 to 30 MOG35-55 model – Least expensive EAE model. Short, very robust. May be used to test neuronal regeneration. Strong demyelination. Excellent therapeutic window.

MOG1-125 model – Similar to MOG35-55 model, but sensitive to B cell targeting.
[Ser140]-PLP139-151/CFA-induced EAE in SJL mice 35 to 60 Relapsing-remitting model. Highly synchronized EAE onset. Very mild demyelination.
Spinal cord homogenate (SCH) induced EAE in Biozzi mice 80 Secondary progressive EAE. Treatment typically starts ~50 days after immunization.
MOG35-55 induced EAE in NOD mice 60 Secondary progressive EAE. Treatment typically starts ~35 days after immunization.

Ex vivo T cell function analysis

Evaluates effect of compounds on T cell function, measured after in vitro antigen (re-) stimulation of spleen or LN cells. Provides insight into mechanism of action.

Variant Description
After restimulation with glatiramer acetate (GA) Cells from mice immunized with glatiramer acetate are restimulated with GA. Compares ability of different GA lots to stimulate IL-2 production.
After restimulation of antigen-primed T cells Immunized (antigen-primed) or naïve mice are treated in vivo. Cells from these mice are then (re-) stimulated in vitro, and cytokine production and proliferation measured. Cells can also be stimulated in the presence of test compounds.
After stimulation of naïve T cells

Graft-versus-host disease in mice

Acute or chronic GvHD is induced in mice using allogeneic or xenogeneic grafts with or without irradiating recipient mice. The severity of GvHD is influenced by the number of cells transferred and the dose of irradiation used to facilitate donor cell engraftment.

Model Description
Acute xenogeneic GvHD in NOG mice NOG (NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac) recipient mice may optionally be irradiated, and injected with human peripheral blood mononuclear cells.
Chronic allogeneic GvHD in mice - under development (2023) Cells from donor mice with mismatched major histocompatibility complex (MHC) or minor histocompatibility antigens are injected into recipient mice. Recipients may be irradiated before cell transfer to prevent graft rejection.

Gut homing of cultured T cells

This six day gut homing assay tests effects of compounds or antibodies on cultured T cell homing.

Model Description
Gut homing of cultured T cells T cells from CD45.1+ donor mice are enriched, cultured with anti-CD3/CD28 beads +/− a gut homing inducer (ATRA), and expanded.

The two sets of cells are labelled and transferred 1:1 into CD45.2+ recipient mice. One day later cells from spleens, Peyer's patches, and lamina propria of the small intestines are isolated and the ratio of ATRA-treated CD45.1+ cells to untreated CD45.1+ cells (both originating from donor mice) is determined by flow cytometry.

Inflammatory bowel disease (IBD) models (colitis, Crohn's disease)

IBD is an inflammation of all or part of the gastrointestinal (GI) tract. The most common forms of IBD are ulcerative colitis, which affects the colon, and Crohn's disease, which can affect any part of the GI tract (but most often colon and terminal ileum).

Model Pros/Cons
CD4+CD45RBhigh-induced colitis in SCID mice Closest rodent model to IBD in humans. Good correlation to clinical efficacy in humans; excellent disease development in our hands.
Anti-CD40-induced colitis in RAG2KO mice Short-term model dependent on the innate immune response. Rapid development of proinflammatory cytokines in serum and histopathology in the colon.
DSS-induced colitis in C57BL/6 mice - Effective April 2022, Hooke no longer runs or recommends this model. Click link for details. Similar clinical observations and histopathology to human IBD. Short, robust, inexpensive.

Maximum tolerated dose (MTD)

This seven day assay evaluates compound tolerance in mice or rats. It is used to establish tolerated doses prior to in vivo testing in disease models.

Model Description
Maximum tolerated dose (MTD) Mice or rats are administered test compounds at a range of doses, and observed for side effects.

Passive cutaneous anaphylaxis (PCA)

Short-term assay evaluates effect of test compounds on FcεRI (high-affinity IgE receptor) crosslinking and release of pro-inflammatory mediators.

Model Description
Passive cutaneous anaphylaxis (PCA) PCA is induced in ear by sensitization with anti-DNP IgE monoclonal antibodies, followed by challenge with DNP-HSA (human serum albumin). Usually run in BALB/c mice.

Readouts are ear thickness 1 hour after challenge injection, and Evans blue dye extravasation.

Pharmacokinetics (PK)

Short-term assay used prior to compound testing in vivo to optimize dose, route, and frequency of compound administration.

Model Description
Pharmacokinetics (PK) Mice or rats are administered one dose of compound. Plasma and tissue are collected at multiple timepoints after administration.

Psoriasis models

Commonly used models of human psoriasis.

Model Description
IL-23 induced epidermal hyperplasia in C57BL/6 mice Ears are injected with IL-23 for 4 days. Readouts are ear thickness, cytokine concentration in ear tissue, and histology.
Imiquimod-induced psoriasis in C57BL/6 mice Imiquimod is applied to mouse backs and/or ears for 4 days. Readouts are skin thickness, cytokine concentration in skin tissue, histology, and flow cytometric analysis of ear tissue cells.

Sjögren's syndrome models

Mouse models of Sjögren's syndrome, an autoimmune disease that affects both salivary and lacrimal glands, resulting in dry mouth and dry eyes.

Model Description
Primary Sjögren's syndrome in NOD mice Sjogren syndrome-like disease, characterized by development of inflammation in salivary and lacrimal glands. The disease develops spontaneously in NOD mice by 12 weeks of age.
Secondary Sjögren's syndrome in (NZB x NZW)F1 mice (NZB x NZW)F1 (also called NZBWF1) mice spontaneously develop inflammation in salivary and lacrimal glands by 35 weeks of age.

Systemic lupus erythematosus (SLE) models

SLE is a systemic autoimmune disease which can affect almost any organ. It is characterized by acute and chronic inflammation and the presence of circulating antinuclear antibodies.

Model Pros/Cons
SLE in MRL/lpr mice Relatively short - typically only 6 to 8 weeks of treatment. Caused by a single mutation (unlike SLE in humans).
SLE in (NZB x NZW)F1 mice Disease is polygenic and spontaneous, very similar to SLE in humans. Excellent predictive value for efficacy. Long model (18 to 20 weeks of treatment). Mice also develop inflammation resembling secondary Sjögren's syndrome.

T cell dependent antibody response (TDAR) assay

This assay tests effects of potential therapeutics on B cell activation and differentiation, and antibody production.

Model Description
T cell dependent antibody response (TDAR) assay Tests effects of compounds on antibody production without the use of adjuvant. The assay is also used for immunotoxicity assessment. Treatment starts at time of immunization.

Please contact us at or with questions or for a detailed quotation.

Also, see our CRO FAQ for answers to common questions about doing business with Hooke.