AUGUST 25 • 2022 | 41

HEALTH

R

esearchers at Tel Aviv
University, led by Prof.
Illana Gozes from
the Department of Human
Molecular Genetics and
Biochemistry at the Sackler
Faculty of Medicine and the
Sagol School of Neuroscience,
have unraveled a mecha-
nism shared by mutations in
the genes that cause autism,
schizophrenia and other con-
ditions.
The researchers also found
that an experimental drug
previously developed in Prof.
Gozes’ lab is effective in lab
models for these mutations
and may lead to effective
treatment for a range of rare
syndromes that impair brain
functions, including neuro-
degenerative diseases like
Alzheimer’s.
Participants in the study
recently published a paper that
was in the scientific journal
Molecular Psychiatry.

“Some cases of autism are
caused by mutations in various
genes. Today we know of more
than 100 genetic syndromes
associated with autism, 10 of
which are considered rela-
tively common (though still
extremely rare),” Gozes said.
“In our lab, we focus mainly
on one of these, the ADNP
syndrome, caused by muta-
tions in the ADNP gene,
which disrupt the function of
the ADNP protein, leading to
structural defects in the skele-

ton of neurons in the brain. In
the current study, we identified
a specific mechanism that
causes this damage in muta-
tions in two different genes:
ADNP and SHANK3 — a gene
associated with autism and
schizophrenia. According to
estimates, these two mutations
are responsible for thousands
of cases of autism around the
world.”
Gozes, who is also director
of the Adams Super Center for
Brain Studies at TAU, explains:

“We discovered that in some
mutations, a section added
to the protein protects it and
reduces the damage by con-
necting to a control site of the
neuron’s skeletal system. We
know that this same control
site is found on SHANK3 — a
much-studied protein, with
mutations that are associated
with autism and schizophrenia.
“We concluded that the abil-
ity to bond with SHANK3 and
other similar proteins provides
some protection against the
mutation’s damaging effects.”
At the next stage of the
study, the researchers found
additional sites on the ADNP
protein that can bond with
SHANK3 and similar proteins.
One of these sites is located on
NAP, a section of ADNP that
was developed into an exper-
imental drug (Davunetide) by
Prof. Gozes’ lab.
Moreover, the researchers
demonstrated that extended
treatment with Davunetide sig-
nificantly improved the behav-
ior of model animals with
autism caused by SHANK3.
Prof. Gozes: “In previ-
ous studies we showed that
Davunetide is effective for
treating ADNP syndrome
models. The new study has led
us to believe that it may also be
effective in the case of Phelan
McDermid syndrome, caused
by a mutation in SHANK3, as
well as other syndromes that
cause autism through the same
mechanism.”
The experimental drug
Davunetide was recognized
by the FDA as an orphan and
rare pediatric drug for future
treatment of the developmen-
tal syndrome ADNP and is
protected by patents through
Ramot, the technology transfer
company at Tel Aviv University
and exclusively licensed to
ATED Therapeutics Ltd.

An experimental drug developed at a Tel Aviv University
may be suitable for treating a range of rare syndromes
that impair brain functions.

HEALTH NEWS FROM ISRAEL

Breakthrough
in Brain Research

Professor
Illana Gozes