An impossible mission
On this question of concern to people in Taiwan, Chen says that while 15 years ago it might have been impossible, Taiwan now possesses sufficient sophistication in the biomedical field to develop new drugs. However, the key is that there is a long road that must be traversed from successful development to introduction on the mass market. So unless a total commitment exists, the effort is wasted.
The main obstacles are the numerous restrictions on human trials that currently exist in the laws governing medicines. Human trials are an unavoidable step in the process of bringing a new drug to market. After a drug has passed animal trials, but before human trials commence, an application must be made to the Center for Drug Evaluation (CDE). However, there is an unwritten rule in Taiwan that drugs that have been certified for use in humans by the US Food and Drug Administration will be quickly approved by the CDE, upon which the Department of Health's Bureau of Pharmaceutical Affairs will grant approval for human trials. If such an "endorsement" does not exist, the CDE will examine the effectiveness, risks, ethics and other factors of human trials, expending much time in the process.
At a press conference launching Myozyme in early May, Academia Sinica president Lee Yuan-tseh stated that while in the past Taiwan lacked the ability to develop new drugs, dictating that it rely on foreign certification, the capabilities of the country's academic institutions and industry have already improved to the point that the government's regulatory system needs to be adjusted.
In addition, current medical laws specify that as well as civil liability, doctors face the possibility of criminal prosecution in cases of dispute over medical treatment. For human trials of new drugs, whose results are difficult to predict, such laws undoubtedly present a formidable risk to the physician. If the treatment should happen to fail, the patient can sue, and the doctor faces the possibility of not only having to pay out compensation, but even spending time in prison.
Under such unfavorable circumstances, it is understandable that Taiwan's physicians are reluctant to cooperate with R&D teams and perform human trials. This situation has greatly hindered the development of biomedical technology in Taiwan.
Goal: gene therapy
After the successful development of a treatment for the once-untreatable Pompe disease, National Taiwan University Hospital has led the way in screening newborns for Pompe disease.
Chen points out that recently Dr. Hu Wu-liang of NTUH has discovered two babies with Pompe disease was discovered using this screening process. Fortunately, on the 20th day after birth, both children began to receive treatment so that the adverse effects of the disease could be minimized.
Chen's part of the work in developing a treatment for Pompe disease is complete, yet the final objective has not been reached. He points out that though a drug to treat patients now exists, they must still continue their treatment for their entire lives. Even if Taiwan's National Health Insurance scheme currently covers part of the cost, the time and monetary burdens on patients and their families are still formidable. The only hope for eliminating this burden is developing a workable gene therapy in the future.
Like research on gene therapies for other diseases, research for such a treatment for Pompe disease faces the twin dilemmas of short persistence times and poor therapeutic effectiveness after genes are introduced into the patient's body.
"Current animal experiments show that healthy genes can be successfully introduced to replace defective genes. The problem is that after outside genes are introduced, they are attacked by the patient's own immune cells, so that their therapeutic effect is maintained for only around six months before weakening and then disappearing," Chen explains, admitting that there is still a long way to go before gene therapy for Pompe disease is available.
Besides its efforts in finding treatments for Pompe disease, the Academia Sinica's Institute of Biomedical Sciences, led by Chen, is also working with universities and medical centers on research programs on diseases caused by non-single-gene defects and affected by environmental factors--including diabetes, bipolar disorder, early-onset hypertension, degenerative arthritis of the hand, and obesity, as well as 12 types of adverse drug reactions. The population affected by these conditions is large and represents an enormous potential market. The diseases themselves are likely to have a lasting impact, and will be the institute's focus over the next few years.
Myozyme is simply a beginning. It heralds the arrival of Taiwan's biomedical technology as a force to be reckoned with, and in the future advances can be anticipated.
Pompe disease
Pompe disease is a rare and serious genetic disorder also known as acid maltase deficiency or glycogen storage disease. Because those afflicted lack an enzyme needed to break down glycogen, an excess accumulates in the body, damaging muscular function throughout the body.
The exact prevalence of Pompe disease is unknown, and racial groups differ in their susceptibility. Roughly one in every 40,000 newborns has Pompe disease.
There are two types of Pompe disease: infantile, and late-onset. Infantile Pompe disease is the more serious, and often fatal. Because the young victims do not have the muscular strength to move normally, they are called "floppy babies".
Late-onset Pompe disease may occur at any time from childhood to old age, and progresses more slowly. The course of the disease in different patients varies widely, with some suffering only muscle weakness, while others need a wheelchair or respirator.
Symptoms of infantile Pompe disease include severe muscle weakness, enlarged heart, swollen tongue, enlarged internal organs, and difficulty in breathing. Death usually occurs within one year after symptoms appear, with the immediate cause being cardiopulmonary failure.
The main symptoms of late-onset Pompe disease are muscle weakness, and difficulty in walking or breathing. Heart function is usually normal.
Future research directions for the Institute of Biomedical Sciences
The primary research focus at the Academia Sinica's Institute of Biomedical Sciences is disease affecting humans, with research conducted by eight teams:
Cancer
Cardiovascular
Infectious Disease and Immunology
Neuroscience
Epidemiology and Genetics
Structural Biology
Cell Biology and Signal Transduction
Bioinformatics
The institute's future efforts will be directed toward drawing on the results of many years of accumulated research findings, and coordinating efforts in pathology and genetic research. In the next five years, the institute's genomic medicine research program will focus on three steps:
Screening for new genes and markers for diseases
Determination and analysis of genetic causes of disease
Exploring genes as tools for treating disease