The term rare applies to those diseases that affect a limited number of people, and have a prevalence lower than a legislatively determined threshold in each country. In the EU, this threshold is set at 0.05% of the population, i.e. one case per 2,000 inhabitants. (In the United States a disease is considered to be rare when it has been diagnosed in fewer than 200,000 individuals in the population, i.e. approx 0.08%)
Rare diseases create particular problems because they are rare, serious, frequently chronic and sometimes progressive, and have an onset often at birth or during childhood.
Many who suffer from rare diseases find it difficult to be diagnosed, to obtain information or to be given a referral to qualified specialists. They also have difficulty obtaining access to effective treatment, social and medical care for the disease, coordinating basic treatment with that provided at hospitals, preserving their autonomy, and participating in the labour market as well as in social and community life.
We are dedicating our efforts to the treatment of three rare diseases.
Lipoprotein lipase deficiency, LPLD
Lipoprotein lipase, or LPL, is an enzyme which occurs naturally in the body, in particular in the capillary endothelial cells, and is involved in triglyceride metabolism. These fat molecules, which are a source of energy for the body's cells, are in turn derived from VLDL lipoproteins and chylomicrons.
Lipoprotein lipase deficiency is a rare disease in which patients have a defect in the gene for lipoprotein lipase, the enzyme responsible for fat degradation. People with this condition accumulate very high fat levels in the blood (hyperchylomicronaemia). Patients with this disease have to be on a strict, low-fat diet and risk having recurrent bouts of pancreatitis (inflammation of the pancreas), which is a serious and life-threatening
Limbal stem cell deficiency (LSCD)
The transparency of the cornea is essential to ensure the ability to see properly. Corneal cell renewal and repair are dependent upon the cells present in the limbus, which is found in a small area of the eye between the cornea and the conjunctiva.
Thermal or chemical burns on the eye can destroy the limbus and cause a lack of limbal cells. If this happens, the cornea becomes covered by a different kind of epithelium via an invasion of cells from the conjunctiva. This makes the cornea opaque and leads to vision loss, a condition that cannot be effectively treated with conventional corneal transplantation.
Our therapy is based on cultures of limbal cells taken from the patient, which, once they have successfully grafted, regenerate the corneal epithelium and restore its functions. Limbal cell cultures even allow the possibility of treating patients with a loss of corneal epithelium in both eyes, provided that a small portion of limbus remains in one of the eyes.
Alpha-mannosidosis is a rare and serious hereditary genetic disease resulting from an enzymatic deficiency which causes a build-up of lysosomal enzymes. The disease is generally found in two forms which differ in severity of symptoms and age of onset, and appears either at birth or during early childhood. Its incidence stands at about 1 case for every 500,000 newborns.
Some children are already born with malformations or develop them in their first year, whereas others often do not appear to have problems at birth, but their condition then progressively worsens. The main symptoms of the disease include immunodeficiency, skeletal abnormalities, deafness, gradual impairment of mental and linguistic functions and, often, episodes of psychosis.
Through the acquisition of Zymenex, a Scandinavian biotech company, we intend to provide an answer to this serious condition with a therapy which replaces the missing enzyme, thus acting upon the cause of this disease.
Kidney and liver failure: Organ transplantation
Organ failure means that an organ loses the ability to perform its physiological functions, and this creates a potential threat to the patient's quality of life and survival.
The kidneys have a number of physiological functions, from filtering blood to removing waste products to maintaining electrolyte balance and regulating the production of red blood cells via the hormone erythropoietin. The severity of the renal insufficiency is usually quantified by laboratory analyses, from minor (stages 1–2) to severe chronic renal failure (stage 5). With chronic kidney failure, there are two treatment options, either dialysis or transplantation. The first option is a palliative treatment which involves the use of an external machine that takes over the kidneys’ filtration function. Dialysis is an effective method, although for most patients the frequent hospital visits are time consuming and the treatment is stressful. Transplantation involves an operation in which a new and functioning kidney (transplant) is implanted so that the patient recovers the lost function.
For patients with liver failure, the situation is even more complex. A functioning liver is vital for survival, and for patients with severely impaired liver function, there is no palliative treatment corresponding to kidney dialysis. The only treatment option is therefore transplantation. Unlike kidney transplants, the old liver is removed and replaced with a new one.
Two important limiting factors for transplantation are their availability, which is still much lower than the demand, and the biological and immunological compatibility between the graft and the recipient. Physiologically, the immune system protects the body from external pathogens by being able to distinguish between the host (own tissue) and all that is not (foreign tissue). Though critical in defending a healthy individual, in a transplanted patient receiving a graft from a donor (thus, strictly speaking, non‑self), this mechanism results in the immune system attacking the transplanted organ (rejection).
The current standard treatment to prevent organ rejection comprises a combination of immunosuppressive drugs that lowers the immune system’s reactivity in order to avoid rejection, but not so much as to increase the risk of opportunistic infections. Treatment is maintained as long as the transplanted organ works. The mean survival of a transplanted kidney is about 10 years, while it is slightly shorter for a transplanted liver.
The standard of care currently in use is based on a triple combination of immunosuppressant agents, of which tacrolimus represents the main pillar.