When diseases aren’t caused by chemicals, external allergens or other living organisms like viruses or bacteria, surely the symptoms are limited? Wrong. Painful and dangerous, inflammation can arise out of the blue, and treatment is difficult.
The body’s immune system can be equally as toxic to foreign organisms as it can to its own tissues. A hyperactive immune system, or having certain over-sensitive types of antibodies, can wreak havoc on the body.
We discuss many well-known autoimmune diseases on a regular basis, such as multiple sclerosis, resulting from the attack of the myelin sheath of nerve cells; diabetes mellitus type 1, where the immune system destroys insulin-producing pancreatic cells; rheumatoid arthritis, in which the joints suffer from inflammation; and lupus erythematosus, when the whole body is under attack.
There are many other less well known autoimmune diseases that also take a great toll on patients. We’ve reviewed seven of these conditions that biotech is also fighting to treat. It is often the case that these diseases occur together, as different symptoms arise in different organs which are afflicted by the same set of antibodies.
Various types of autoimmune antibodies can cause inflammation of the thyroid gland, which in response causes deregulation, such as under- or oversecretion, of the hormone thyroxine. Grave’s disease occurs when antibodies activate TSH receptors, which induce the thyroid to secrete too much thyroid hormone.
Typically this condition requires ablation of the gland and then life-long hormone replacement therapy, which can have the opposite effect and induce hypothyroidism. Generally, you don’t hear about thyroid disorders in biotech unless it’s in relation thyroid cancer. The production of synthetic thyroxine (e.g. Levothyroxine) seems to make the search for a cellular therapy for this disease less of a priority.
This is understandable to an extent, as once patients with Grave’s have had the thyroid gland removed, treatment of hypothyroidism is considerably easier than treating certain cancers. Still, Endocrinology is an incredibly complex and nuanced field, and there is an increasing number of patients for which ‘synthroid’ treatment does not work.
This has therefore led to the search for other sources of hormone extract that work better than the traditional pig extract, which contains both types of thyroxine hormone and is dubbed ‘armour’ by Forest Pharmaceuticals.
One common misconception of dermatological conditions like psoriasis is that it’s mostly just cosmetic damage and discomfort the skin plaques cause. Like in burn victims, during flare-ups the skin damage can be very serious, leaving patients unable to regulate their body temperature normally and vulnerable to life-threatening infections.
Today, palliative care is available, while biotech and pharma look for effective treatments. The Danish LEO Pharma has already received approval for its antibody Kyntheum (brodalumab), whereas MorphoSys is working on guselkumab, an antibody that could outperform the best-selling drug, AbbVie’s Humira, in many inflammatory conditions including psoriasis.
Meanwhile, Samsung Bioepis has launched a biosimilar of Janssen’s Remicade (infliximab), driving down the high price tag of psoriasis treatments. Other companies working in this field include Delenex Therapeutics, Sweden-based Affibody, and Switch Biotech in Germany. You can read more on the National Psoriasis Foundation.
Responsible for 10-15% legal blindness in developed countries, uveitis is used as a general term for the inflammation of the uvea, optic nerve and vitreous of the eye. Its general treatment of uveitis is anti-inflammatory corticosteroid eye drops. The disease can be caused by a variety of other autoimmune diseases including Crohn’s disease and sarcoidosis.
Novartis’ secukinumab, an antibody that binds to interleukin (IL)-17A, is being investigated for uveitis as well as psoriasis. AbbVie, on the other hand, has a Phase III trial ongoing with its candidate adalimumab. TxCell, from Nice, France, has been granted EU and US Orphan Drug Designation for its T-cell based therapy for autoimmune uveitis. Then there is Apitope in the UK, which has a T-cell immunotherapy which is also being investigated for psoriasis and Grave’s disease.
Sarcoidosis is a poorly understood inflammatory condition in which inflammatory cells build up in certain tissues, particularly the lungs, to form granulomas. These most commonly cause respiratory problems and chest pain, although they can also occur in any other tissues, including the brain.
Janssen has investigated Remicade (infliximab) for pulmonary sarcoidosis, and acquired Centocor, which had its own antibodies, ustekinumab and golimumab, in Phase II).
Celgene, in the US, has also had a rich history of investigating therapeutics for sarcoidosis, although most trials were withdrawn for various reasons. This included an effective Phase III small-molecule inhibitor, CC-100004, which although it managed to reduce inflammation in sarcoidosis, also had various adverse effects limiting its use.
AbbVie’s Humira (adalimumab) was also proposed for a trial in sarcoidosis by the University of Chicago, but terminated due to the failure to recruit enough patients in 2011.
Addison’s disease is another example of endocrine deregulation, caused by the attack of the enzyme 21-hydroxylase in the adrenal cortex, which impairs its function. This can cause a range of symptoms including weakness (due to a lack of adrenaline and cortisol), pain, low blood pressure (due to salt loss) and hyperpigmentation of areas of the skin. Crises can also occur when the hormone levels drop too low.
Although treatable with regular hormone replacement therapy to replace cortisol, life-long treatment can be cumbersome and similarly to diabetics, patients have to carry around syringes of cortisol for emergency use. Addison’s seems to face the same situation as for thyroiditis and Grave’s disease: although hormone replacement therapy is life-long, finding an antibody therapy to help manage the disease is less of a priority compared to other autoimmune indications.
Vitiligo is often mistaken for hyperpigmentation of the skin, but is in fact the opposite — the loss of skin pigment. Phototherapy and topical agents such as corticosteroids are normally prescribed, but there is still no effective and safe treatment for this disease.
Fashion model Chantelle Brown is known for speaking up about her vitiligo and how the disease affects the health of sufferers as well as the social problems people with vitiligo have to face.
Leaving aside short term side effects such as erythema and sunburn, which are reversible and infrequent, the main problem with phototherapy is represented by the cumulative long term effects of UV therapy. This can cause premature aging of the skin and risk of skin cancer. Therefore, the aim is to get the best results from phototherapy whilst limiting its length.
The University of Navarra is one example of an institution looking at grafting of autologous (patient derived) melanocytes into afflicted areas of skin in a Phase I/II trial. Otherwise, the Australian biopharma Clinuvel Pharmaceuticals has a candidate called SCENESSE, a chemical analog of α-MSH which was recently granted EMA authorization.
Granulomatosis is a type of vasculitis which encompasses many syndromes and diseases, some of which are poorly understood and have no clinical trials in place, e.g. Cogen’s syndrome. Caused by the inflammation of blood vessels, the symptoms can arise in multiple tissues and cause many knock-on pathologies. You can read more about these diseases on Vasculitis UK.
The US biotech Kineta and the University of Groningen, in the Netherlands are researching a drug derived from sea anemones that was found to have a positive effect on the complications derived from granulomatosis. The NIAD has also run multiple trials for the disease, including a Phase I trial for rituximab in patients with relapsed cases as well as with daclizumab for Wegener’s granulomatosis.
Obviously, these are just a few examples, there are plenty more conditions worth writing about, from Sjögren’s syndrome to Hashimoto’s thyroiditis. But instead, what I found when writing this short review, was that it surprising how large a gap in the biotech field there was for endocrine disorders like Addison’s and Grave’s. It would be interesting to hear some of your thoughts on this!
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