The results of a Phase 2 clinical trial recently published in the Orphanet Journal of Rare Diseases opens new avenues for the development of effective therapies for rare diseases, a field where unmet needs are common.

Thousands of rare diseases have been identified to date and only a handful of them benefit from targeted therapies developed for them specifically, despite favourable regulations and incentives set up to motivate Industry.

Drug development is insufficient not just because of the modest size of each market; there are many other factors complicating the R&D process. These include the lack of knowledge of the natural history of each disease, the scarcity of clinical data, the small number of patients possibly involved in trials and the rarity of professional experts. These areas are also often considered by research funders as too specific and with low potential impact, creating further difficulties for funding basic and preclinical research.

Given these factors, it is highly unlikely that we will see the development of specific innovations for every rare disease. And those treatments that finally overcome these challenges are often too costly to be financially acceptable for health care systems.

The objective for the rare disease community is to find ways to re-purpose already known drugs on the basis of what is now known about these diseases. Today our knowledge is increasing quite quickly in this domain thanks to genetic sequencing efforts.

This is the approach which was chosen to find a therapy for Charcot-Marie-Tooth disease, a rare genetic condition that leads to loss of nerve fibers, muscle wasting and weakness. The researchers combined three compounds, each of them likely to act on the pathway involved in the production of different symptoms.

The concept of using a combination of products is, in a sense, an old one, used by physicians every day when treating patients with common diseases. But it is totally new to test, as a basic concept, the effect of combining products that were selected for their potential action on individual elements of the biological pathway. This approach combines all compounds with top level research discoveries.

There are plenty of rare diseases which could benefit from such an approach. Access to databases on compounds, biological pathways and genetic information, together with appropriate calculations, allows researchers to identify targets and potential compounds able to interact with them.

Many researchers were looking for the one compound likely to have a major effect. They now should look at all possible compounds and combine them, as each of them individually may have a limited effect, but used together they could provide significant benefits for the patient. This is the outcome that is now sought.

Image credit: e-Magine Art. Licensed under CC 2.0