 |
Publications
The World’s First Myoblast
Study of Type II Diabetic Patients
a report by
PeterK Law, PhD, Danlin Min Law, MD, Lu Ping, MD, Guo Jie,
MD, Lu Ying, MD, Xue Yan Feng, MD and Li Xun, MD
Cell Transplants Asia Limited
and Chinese Association of Medicinal Biotechnology, Southern
Center of Biologic Diagnosis and Therapy, China
Type II diabetes, also called
non-insulin-dependent diabetes mellitus (NIDDM), is characterized
by high blood glucose resulting from the genetic defect of
the GLUT4 genome. The latter is manifested in the diminished
glucose uptake into skeletal muscles. In normal human beings,
insulin combines with insulin receptors to change the membrane
conformation of skeletal muscle fibers, allowing blood glucose
to move down its concentration gradient into the fibers for
metabolism. A disorder called ‘insulin resistance’
exists in Type II diabetic patients in which normal or even
elevated levels of plasma insulin would not elicit normal
glucose uptake into the muscle fibers. This article hypothesizes
that these diabetic fibers exhibit less insulin receptors,
or that these receptors exhibit abnormal molecular conformation,
or both. Considering that highly metabolic muscle fibers constitute
more than 50% of the human body by volume and weight, failure
of blood glucose to gain entry would undoubtedly lead to high
blood glucose and result in various organ failures sequentially.
This is not the only defect, but it is likely the primary
and significant one.
A potential genetic treatment
of the disease involves myoblast transfer therapy (MTT) which
is a platform technology of cell transplantation, genome therapy
and tissue engineering.1,2 It consists of culturing immature
muscle cells called myoblasts, derived originally from a 2g
skeletal muscle biopsy from a healthy, young, male donor,
and implanting them into the major muscle groups of the upper
and lower extremities of the diabetic patients. The myoblasts
exhibit natural cell fusion, and transfer their nuclei carrying
the normal human genome into the host skeletal muscle fibers
to effect genetic repair. Others fuse among themselves to
form new myofibers that exhibit normal insulin receptors of
donor origin. Through both mechanisms, new insulin receptors
of donor origin that are genetically normal, will be produced
in the skeletal myofibers of the host.
The survival, development, and
functioning of the implanted allogeneic myoblasts have previously
been demonstrated in studies involving about 240 muscular
dystrophy subjects and two chronically myocardial infracted
heart subjects with 100% safety and substantial efficacy results.3,4
Immunorejection was minimized using two months of cyclosporine
following MTT. In addition, over 120 ischemic heart patients
have received autologous myoblasts in their hearts in 10 countries.
Mortality rate has been less than 10% traversing the last
four years, with efficacy data being collected in Phase II
clinical trials in Europe. Reported here are the world’s
first genetic transplants of two Type II diabetic patients
using allogeneic myoblasts.
|
