Laron Syndrome (Dwarfism) caused by IGF-1 Deficiency Protects People from Cancer and Diabetes, and Prolongs Life Span.

Dr. Jamie Guevara of the Ecuador Institute of Endocrinology measures the
height of patients with Laron Syndrome (Dwarfism). They all share the same
genetic mutation that blocks the growth hormone (GH) receptors in their
bodies. This mutation eventually causes IGF-1 (insulin-like growth factor)
deficiency.

Guevara first began working with the patients from Southern Ecuador
in the 1980s. After 10 years of research he began to notice a pattern:
None of the Laron dwarfs seemed to get cancer or diabetes.
(Jeffrey Kofman/ABC News)


Hormones (Athens). 2008 ;7 :24-7.

The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency.

Zvi Laron

Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center
of Israel, Petah Tikva, Sackler Faculty of Medicine, Tel Aviv University,
Israel. laronz@clalit.org.il

Inactivation of the IGF1 gene or of the GH receptor in both invertebrates
(nematodes-C. elegans, flies-Drosphila) and rodents (mice and rats), leading to IGF1
deficiency, prolong life, particularly in females.

In man, evaluation of the 2 largest cohorts of patients with Laron syndrome
(inactive GH receptor resulting in IGF1 deficiency) in Israel and Ecuador
revealed that despite their dwarfism (and marked obesity), patients are
alive at the ages of 75-78 years, with some having reached even more advanced
ages. It is assumed that a major contributing factor is their protection
from cancer, a major cause of death in the general population.


IGF1-PAK1-Foxo Signaling Pathways Controlling both Cancer and Life Span

According to recent study in the nematode C. elegans, IGF-1 activates the
oncogenic kinase PAK1 that normally inactivates Foxo, a tumor suppressing
transcription factor, which normally blocks malignant growth of cells and
prolongs life span. Thus, IGF-1 deficiency in Laron Syndrome would inactivate
PAK1, leading to the reactivation of Foxo, thereby suppressing cancer growth and prolong life span.

So if we treat cancer patients (adults) with anti-IGF-1 drugs or anti-PAK1
drugs, we could cure cancers and prolong their life span, without causing
such a dwarfism. Thus, several anti-PAK1 drugs have been developed or identified
among antibiotics. Among them, a unique ring peptide called FK228 is so
far the most potent, that blocks the oncogenic PAK1 by inhibiting HDAC (histone
deacetylase). However, FK228 is still in clinical trials (phase 2) mainly
for CTCL (cutaneous T-cell lymphoma), and not available on the market. 

We have recently found that two propolis extracts, Bio 30 from New Zealand
(NZ) and GPE (green propolis extract) from Brazil, block selectively PAK1
signaling pathways, and almost completely suppress the growth of PAK1-dependent
tumors such as NF, pancreatic and breast cancer, and glioma xenografts in
mice. Both Bio 30 and GPE are now available on the market (internet sale)
from Manuka Health in NZ and Yamada Bee Farm in Japan, respectively.

It is now clear that more than 70% of all human cancers require PAK1 for
their growth. These PAK1-dependent cancers include breast and prostate cancers,
colon, pancreatic and ovarian cancers, glioma, melanoma, and MM (multiple-myeloma)
.

Common in Beekeepers and Laron Dwarfs

Very interestingly, like Laron Dwarfs, honeybee keepers never catch cancer,
or only one in 3,000 keepers, far less than general population (one in
3-4 people). It is most likely that propolis protects beekeepers from cancers.
For none of other bee products such as honey, royal jelly, and bee venom has
any anti-cancer activity. Bio 30 is CAPE (caffeic acid phenethyl ester)-rich
propolis, whereas GPE is ARC (artepillin C)-rich propolis. Both CAPE and
ARC are anti-cancer polyphenols that block PAK1.


The highest in the world

Late Sir Edmund Hillary (1919- 2008), who scaled Mt. Everest (8850 m) for
the first time with his Sherpa, Tenzing Norgay in 1953, never got cancer,
though he was very "tall" (and slender). He used to keep honey bees near
Auckland in NZ.

CAPE comes mainly from young buds of poplar trees. The CAPE content of NZ
propolis such as Bio 30 is the highest among propolis samples around the world.

Continued