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Applied Design

Overview

Product design has been at the front of our project since we came up with our initial ideas. We wanted to spend our summer creating a solution to a real world problem that affects a large proportion of the world’s population. In creating a realistic therapeutic product we have looked into current treatments, safety, manufacture, accessibility and the next stage for the product, throughout each stage we have had the patient at the forefront of our minds. After a range of ideas we have settled on a final design for a new therapeutic to treat IBD.

Autoimmune Disease Survey

We received 48 responses from members of the public suffering from autoimmune diseases from a range of age groups. The responses gave us a greater understanding of the current treatments, the problems with them and what patients would like from a treatment. We were astounded by the positivity towards GE and for our project. There is a great deal of belief from the public in the potential of GE in medicine.

They survey told us the public wanted a treatment that treats “a condition at its source rather than masking symptoms.” that was also “less invasive and less dangerous”. They also showed support of a device that was able to provide personalised doses according to the patient. From these results we were able to begin the design of our treatment.

Safety

Safety of the product was the main concern raised in the survey. The majority of people are not highly knowledgeable about genetic engineering so we believe it is especially important to make safety a priority due to the apprehension towards the topic. We aimed to promote the safety of GE probiotics and make it clear that the patient's genome will be unaffected.

Concern on what we would engineer lead to greater investigation into species and strains of bacteria we would engineer with a focus on the safety. We also were directed into investigating how our product would alter the natural balance of the microbiome and how we can reduce any possible negative interactions. This is also why we began our initial research into how to test the safety of the product, we realise this is an important issue and aimed to create a plan to ensure the efficacy and safety to the patient and environment.

This led to us modifying our device to include a kill switch for biosafety.

Autoimmune Diseases

Our survey was completed by people suffering from a range of autoimmune conditions. We realised that our initial idea of a general treatment was over ambitious. Many of the responses said that they would feel more comfortable if the treatment was designed with a greater focus on select conditions.

We have specifically designed our treatment with Crohn’s disease and Ulcerative Colitis in mind, however, we also found how closely related other autoimmune diseases are and decided to look into which conditions we have the potential of treating if we were to develop our treatment further. Our treatment has a huge range of applications. For our initial market we would focus on IBD but the range of diseases affected by the intestinal immune system allows our product to be modified for trials on other relevant autoimmune conditions.

Autoimmune enteropathy, Coeliac disease, Rheumatoid Arthritis, Multiple sclerosis, Psoriasis and Type 1 diabetes have all been shown to linked to the balance between intestinal Th17 and Treg populations (or IL10 concentration) in the gut. For Coeliac disease we may also need to combine our system with a mechanism to digest or modify gluten. Other conditions, such as Microscopic colitis, Lupus and Hashimoto’s thyroiditis, also relate to at least one of these populations but more research will be needed to find how they are connected to the gut. As well as this, specific probiotics have been shown to be beneficial in a range of these conditions. Our device may act as an appropriate treatment with some minor modifications for these conditions. An imbalance in the immune cells in the gut has been shown to cause an autoimmune condition in the kidneys due to migration of Th17 cells showing the importance of population control in the gut.

Types of epilepsy have also been found to relate autoimmunity in the gut. The gut-brain axis may connect autoimmunity in the gut to nervous system diseases and promote Th17 cells in the CNS, similar to what has been found with multiple sclerosis. 80% of cases of epilepsy are in the developing world, this is thought to be due to the influence of bacteria, such as segmented filamentous bacteria (SFB), from water sources influencing the gut microbiome and immune cells. The recent and sharp increase in cases shows the necessity of a simple and effective treatment. If the condition is confirmed to be linked to autoimmunity in the gut then our product can offer an easily administered treatment that stops the disease at its source.

We created table to illustrate which autoimmune diseases have been found to be linked to immune cell balance in the gut:

Condition	Linked to the microbiome	Linked to increased intestinal Th17	Linked to decreased intestinal IL10	Reference
Crohn's Disease	✔	✔	✔	A
Ulcerative Colitis	✔	✔	✔	A
Autoimmune Enteropathy	✔	✔	✔	B
Coeliac Disease	✔	✔	✔	C, D
Microscopic Colitis	✔	✔		E
Rheumatoid Arthritis	✔	✔	✔	F, G
Psoriasis	✔	✔	✔	H, I
Multiple Sclerosis	✔	✔	✔	J, K
Lupus	✔	✔		L, M
Graves' Disease	✔	✔	✔	N
Hashimoto's Thyroiditis	✔	✔	✔	N
Type 1 Diabetes	✔	✔	✔	O
Myasthenia Gravis	✔	✔	✔	N, P

Current Treatments

To ensure the necessity of a novel treatment we looked into what is currently available and the efficacy and side effects of current therapies. We had already learnt a lot about treatments out of our survey for autoimmune patients. The survey told us that the majority of patients use a combination of treatments and highlighted the problems with their treatments.

Treatment Delivery Action Success Side Effects

Aminosalicylates (5-ASAS) Oral/suppository/enema Reduces Inflammation Works for 7 out of 10 mild cases. Ineffective for severe IBD or in maintaining remission Rarely Serious

Immunosuppressants Tablet Reduces the activity of the immune system Effective after 2-3 months Vulnerable to infection, low red blood cell production

Corticosteroids Oral/suppository/enema/IV Reduces Inflammation Short term: acne, weight gain, mood changes,insomnia Long term: osteoporosis, cataracts

Ciclosporin Tablet/7 day infusion Strong immunosuppressant Short term: tremor, hair growth, swollen gum, feeling/being sick, diarrhoea Long term: High blood pressure, reduced kidney/liver function

Biologics Infusion/injection Block receptors for inflammation stimulating proteins Increased risk of infection, vertigo, dizziness, allergy-like reaction

Surgery Colectomy/ileostomy Relieve symptoms but they usually come back Patient spends a week in hospital and a few months recovering

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