Niemann-Pick type C
What is a clinical trial?
Clinical trials are investigations to evaluate new ways to prevent, diagnose or treat diseases in human patients or healthy volunteers. They test medical devices, products or techniques, or they explore new ways of using existing treatments, or combinations of different treatments. Based on the results of clinical trials, scientists can evaluate treatments in relation to both safety and effectiveness. Clinical trials are launched when there is good evidence from laboratory (or other preliminary) studies to suggest that the intervention being tested is an improvement on the current best practice.
Clinical trials are sometimes referred to as ‘clinical studies’, ‘medical research trials’ or simply ‘trials’. Almost all the pharmaceuticals that we use today can be traced back to the results of clinical trials conducted in the past.
Normally, there are four phases in the clinical trial process, referred to as Phases I-IV. Each phase of a clinical trial has a different purpose and helps scientists to find answers to various questions.
is to test the safety and possible side effects of a new treatment or intervention, and to identify the best dose to administer.
is to test if the treatment or intervention is effective against the disease and to find out more about the safety and dosage.
is to compare the new treatment with the current best practice and identify if it’s more effective. Phase III trials usually recruit large numbers of patients from many different sites because it can be difficult to compare the two categories of treatment with small groups. Patients are usually randomised, which means they are assigned to a treatment category (new treatment or current best practice) at random.
is usually carried out after an intervention has been approved for use. Phase IV trials are typically used to study if a treatment works for a wider range of uses, or to understand its long-term effects.
Arimoclomol is an ‘investigative medicinal product’, meaning it is not an approved medicine. We are conducting clinical studies to investigate how effective arimoclomol is as a treatment for a number of diseases. To be approved, all new therapies must be effective and must not cause undue harm. We have studied arimoclomol’s effects thoroughly in the laboratory and are now investigating its effects and safety in patients.
Arimoclomol is a small molecule, which readily distributes around the body, including crossing the blood-brain barrier. It is soluble, and has almost no taste or smell, which means it can easily be dissolved in a drink or suitable food.
Many lysosomal storage diseases are caused by mutations in a protein involved in lipid digestion and transportation. This causes an accumulation of lipid in compartments of the cell called lysosomes, which in turn leads to cell stress and toxicity. When stressed cells are treated with arimoclomol, they are stimulated to produce a natural chaperone called Heat Shock Protein 70 (HSP70), which helps to fold the digestive enzyme into a functional conformation, allowing the cell to process the accumulated lipid.
In rare circumstances, some proteins are vulnerable to aggregation, meaning they clump together and don’t get recycled properly. Aggregations of misfolded proteins cause cell stress, and eventually cell death. When stressed cells are treated with arimoclomol, they are stimulated to produce a natural chaperone called Heat Shock Protein 70 (HSP70), which helps to guide aggregated proteins into the recycling pathway and prevents newly-built proteins from aggregating.
The safety profile of arimoclomol has been extensively explored and confirmed in multiple pre-clinical and phase I clinical studies. The compound has been investigated in pre-clinical toxicity studies, in extensive Phase I studies in healthy adults as well as in Phase II studies in ALS. A total of more than 200 patients have been exposed to arimoclomol for up to a year. No major safety concerns were observed in any of the patients as a result of arimoclomol.