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