Amyotrophic Lateral Sclerosis
ALS is a neurodegenerative disease characterised by progressive muscular paralysis. It is a devastating disease that leads to muscle weakness, difficulty in swallowing, talking and eventually paralysis and death. Most people who develop ALS are between the age of 40 and 70, with an average age of 55 at the time of diagnosis. However, there are cases of the disease striking persons in their twenties and thirties. Overall, there is a slight male prevalence (M:F ratio~1.5:1).
Currently there is only one drug therapy approved in ALS, which extends life by 3 months only. However, with increasing scientific knowledge and potential to translate this in ALS therapy, we foresee a revolutionary change in ALS treatment.
Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to muscle weakness and wasting, where the symptoms may start in the upper and lower limbs. Gradually, spasticity may develop, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present difficulties in speech and swallowing. Limb symptoms can occur almost simultaneously with bulbar symptoms and in the vast majority of cases will manifest within 1–2 years. Paralysis is progressive and leads to death, due to respiratory failure, within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases.
Incidence of ALS – an orphan disease
Most of the research on prevalence and incidence numbers of ALS has been performed in Europe. It appears that the diversity of ALS epidemiology is related to the population demographics. Also, ALS is more common among the elderly, thus in light of the global trend of increasing life expectancy the incidence numbers may increase. Other factors that have been considered to be related to the occurrence of ALS are environmental risk factors, geographical differences and genomic epidemiology.
A review of published incidence and prevalence literature in Europe and the US revealed that the median incidence rate in Europe is 2.7/100,000 person years resulting in 15.355 estimated cases. Median prevalence is 5.4/100,000 person years corresponding to 39.863 cases (Chiò, et al., 2013). In the US these numbers are similar as the incidence is 10.131 cases annually and the prevalence is 36,480 cases (Borlongan, et al., 2013). Thus, in the Western world approximately 75,000 patients are currently eligible for new drug therapy.
Given its prevalence, ALS is an orphan or rare disease. From a regulatory perspective rare (or orphan) diseases are defined as those affecting less than 200,000 patients in the US or no more than five out of 10,000 of the general population in the EU. Nowadays, a number of unique clinical, regulatory and commercial challenges are associated with the development of therapies for rare diseases.