Rare Diseases Knowledge

The definition of rare disease differs from country to country, but it generally refers to diseases with between one to eight patients for every 10,000 people.^[1]
The government of Hong Kong has not established any official definitions of rare disease. The lack of definition denies many patients of a timely diagnosis, publicly funded medication and adequate social support.

^[1] Aronson, J. K. (2006). Rare diseases and orphan drugs. British Journal of Clinical Pharmacology, 61: 243-245. doi:10.1111/j.1365-2125.2006.02617.x

There are between 6,000 and 8,000 rare diseases that are now recognised by the international community, among which 467 were identified in Hong Kong as of 2016. New types of rare diseases continued to be discovered every year worldwide.^[1]

^[1] Chiu, A., Chung, C., Wong, W., Lee, S. L., & Chung, B. (2018). Healthcare burden of rare diseases in Hong Kong – adopting ORPHAcodes in ICD-10 based healthcare administrative datasets. Orphanet journal of rare diseases, 13(1), 147. doi:10.1186/s13023-018-0892-5

Nearly all rare diseases are caused of genetic defects or mutation.^[1] These can be passed onto one generation from the other.
A very small minority of rare diseases can be caused by a variety of reasons including but not limited to rare forms of infection, allergies and environmental factors.
In many cases, the exact cause remains unknown.

^[1] Abbott, A. (2011). Rare-disease project has global ambitions, 472: 17. doi:10.1038/472017a

Some rare diseases identified in Hong Kong include Mucopolysaccharidosis, Pompe Disease, Infantile Cutaneous and Articular Syndrome, Tuberous Sclerosis Complex, Myelofibrosis, Marfan Syndrome, Rett Syndrome, Spinocerebellar Ataxia, Fabry Disease, Gaucher Disease, Achondroplasia, various forms of Osteochondrodysplasias, C9ALS/FTD, Myotonic Dystrophy and Huntington’s Disease.

Most rare diseases are unfortunately without treatment. For a lot of pharmaceutical companies, the number of patients of specific rare diseases is too small for the research and development of orphan drugs to be cost effective. The development of treatment therefore relies on public funding, government initiatives and private donations, which makes it an uphill battle. Although most rare diseases cannot be cured, for many cases an early diagnosis and proper medication can help control the disease and drastically slow down deterioration.

Developing patient registry is the cornerstone of all medical research studies. Patient registries gather essential data for theoretic and clinical research. Since 2010, NRND has put in considerable effort in establishing a patient registry for SCA. Through the patient registry, dozens of patients obtained a definite diagnosis and new mutations have even been identified (See Our Research Project). The registry also gives researchers access to a larger gene pool, with which much research can be done to better understand the diseases. NRND hopes to expand the patient registry to other diseases, which will extensively aid researchers to study the underlying causes of rare diseases.

Another important facet of the work of NRND is of course the research and development of novel drug candidates. Apart from P3, AQAMAN and BIND , members of NRND have also discovered the following drug candidates and are assisting in their drug development:

For C9ALS/FTD:
– BIND

For myotonic dystrophy type 1:
– Oligomer 4  
– PLG50-1/5, PDG50-1/5, PDLG50-1/5
– 1a and 2a
– Ligand 3  
– Ligand 5, 6 and 9  

For multiple polyQ diseases, such as Huntington’s disease and several types of spinocerebellar ataxias
– DB213

Developing a new drug from conception to approval for marketing takes around 15 to 16 years.

Upon finding a novel drug candidate, which takes several years of research, pre-clinical studies are initiated to evaluate its potential effectiveness. These studies are carried out in vitro (within the laboratory) as well as in animals and would normally take 5-6 years.^[1] This stage is called “pre-clinical studies” and makes up the everyday work of NRND. Once various parameters are assessed (safety, carcinogenicity etc), clinical studies will begin.

Clinical studies are phases of studies on human that focus on different pharmaceutical aspects. Phase 1 focuses on the safety of the drug candidate, its performance and effects on the body, and the determination of dosage. Phase 1 may take several months or more. Phase 2 focuses on the effectiveness of the drug, whether it does what it intends to on patients with the targeted disease and with what kind of side effects. This phase can take up to a few years. The third phase of clinical studies is to confirm the drug’s efficacy, evaluate safety and prove that regulatory requirements are met. It is an extensive process that typically takes several years, in multiple medical institutions and with as many patients as possible.^[2] This drug can be marketed when the third phase clinical test is passed, and the drug approved. All three phases of clinical trials take eight to ten years on average.^[3] Some drugs are required to undergo on-going post-market surveillance.

From initial discovery to the marketplace, introducing a new medicine successfully takes therefore 15 to 16 years. Many studies come to a halt during clinical studies because of scientific or bureaucratic hurdle. Indeed, only around 13.8% of drug development programmes make it from Phase 1 Clinical Studies to marketing, not to mention those that fail pre-clinical studies before clinical studies even begin.

^[1] Coloma, Preciosa. (2013). Phase 0 clinical trials: Theoretical and practical implications in oncologic drug development. Open Access Journal of Clinical Trials. 5. 119-126. 10.2147/OAJCT.S32978.

^[2] Institute of Medicine (US) Committee on Accelerating Rare Diseases Research and Orphan Product Development; Field MJ, Boat TF, editors. Rare Diseases and Orphan Products: Accelerating Research and Development. Washington (DC): National Academies Press (US); 2010. 5, Development of New Therapeutic Drugs and Biologics for Rare Diseases. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56179/

^[3] Coloma, Preciosa. (2013). Phase 0 clinical trials: Theoretical and practical implications in oncologic drug development. Open Access Journal of Clinical Trials. 5. 119-126. 10.2147/OAJCT.S32978.

An early diagnosis of inherited rare diseases often means a timely treatment and improved care for patients of rare diseases and their family. If you have family members who have histories of rare diseases, genetic testing can ensure an early diagnosis.