2001 - Mark Babizhayev MA, PhD, Live Interview
In this interview, Pharmacist Phil Micans, interviews Dr. Mark Babizhayev,
MA, Ph.D, ExecutiveDirector
of Innovative Vision Products and Senior Research Investigator at the
prestigious Helmholtz Research Institute of Eye Disease in Moscow, about
the research and development of this new breakthrough in the non-surgical
treatment of age related cataracts.
"Dr. Babizhayev thank you for being kind enough to undertake this interview.
Babizhayev: "You're welcome."
"Perhaps I could start by asking you to please tell our readers how many
years you have been involved in the research with NAC?" [Ed.- n-acetylcarnosine].
Babizhayev: "We started our work on N-acetylcarnosine as
a potent ophthalmic drug in 1991, after we concluded the contract relations
with the executives Dr. Edoardo Bozzo Costa and Mr. Ovidio Caveri of Bruschettini
S.r.l., Genoa, Italy."
Treatment of human cataract with 1% n-acetylcarnosine eye
drops over period of 5 months.
image shows that this opacity has disappeared after the cited
period after treatment with n-acetylcarnosine is completed. The lens
has become clearer.
image shows the appearance of cataract which resembles a bat
in its form.
"In all that time, when did you first realize that NAC was something special
for the treatment of cataract?"
Babizhayev: "We initially realized that NAC was promising
for the treatment of human cataracts when the first pharmacokinetic studies
were completed. They showed that NAC can act in-vivo as a pro-drug of L-carnosine
in ophthalmic application, as an antioxidant." [Ed.- Clin. Chim. Acta 1996,
"Presumably, your first experiments were undertaken with animals? Would
you like to elaborate on some of the results you obtained?"
Babizhayev: "The NAC anti-cataract eye drops have been carefully
tested in animals. We have processed the treatment of age-related cataracts
in canines and experimental models of cataract in rabbits. The most striking
results have been obtained using a 1% NAC instillation in canines with age-related
cataracts. We have determined the efficacy of cataract treatment, and we have
revealed a new phenomenon of melting snow upon the instillation of NAC, for
the chronic treatment of cataract within only 1-month [Ed.- see photos]. The
cortical appearance of cataract reversal starts from the periphery and then
the lens becomes more transparent. This is then accompanied by the improved
visual behavior of the animal. Rigorous computerized image analysis have been
supplied to support the evidence of the cataract treatment in rabbits [Ed.-
see photos]. The striking results of reversing cataract and the prevention of
the lens opacities are clear, and have been revealed in traumatic and liposome-induced
types of modeling cataract.clinical
"Later of course, you were also involved with NAC eye-drops in human trials,
what kind of results did you get there?"
Babizhayev: "First we developed sensitive measurements for
the lens opacities in humans. These were original techniques of glare tests
[Ed.- see figure]; they are very sensitive to even tiny changes of the lens
opacities and we also tested the macular function, which is the vision behind
the cataract. We have also utilized stereocinematographic slit-image and retro-illumination
photography, with subsequent interactive digital image analysis and 3D computer
graphics for the lens light scattering, or absorption. The intra-reader reproducibility
of the measuring techniques for cataractous changes was good. One group of patients
were the control reference group, they demonstrated the variability in densitometric
readings of lens clouding and they had negative advance in glare sensitivity
at 6 months, and a gradual deterioration of visual acuity and gross transmissivity
of lenses at 24 months, these results were compared at baseline and 6-month
follow-up examinations. However, when compared with baseline examination at
6 months, 41.5% of the eyes treated with NAC eye drops presented a significant
improvement in visual acuity of 7-100% and 88.9% of the eyes ranged a 27-100%
improvement in glare sensitivity. Topographic study demonstrated less density
and corresponding areas of opacification in posterior subcapsular and cortical
morphological regions of the lens. That is consistent with visual acuity up
to 0.3. The total study period was over 24 months and it revealed that the beneficial
effect of NAC is sustainable. Image analytical readings of lenses indicated
that no cases resulted in a worsening of visual acuity for the NAC-treated group
of patients, and in most of the patients drug tolerance was good. Statistical
analysis revealed significant differences between 6 and 24 months as an overall
cumulative and positive change of the characteristics of cataracts in the NAC-treated
group, when compared to the control group. The synthesized N-acetylated
carnosine eye drops are therefore proposed as an effective and physiologically
acceptable drug for non-surgical treatment of age related cataracts."
"Were there any side-effects noted in the human trials?"
Babizhayev: "For most of the patients treated, drug tolerance
was good and no side effects were associated with the application of 1% NAC.
What is more, no recurrence of cataract development occurred during the period
of NAC application."
shows the reduction of cataract in canine eyes.
picture: Shows canine cataract before treatment with n-acetylcarnosine
picture: Shows results of the treatment after only 1 month. Already
we begin to see the break-up of the impaired proteins - an effect that for obvious
reasons has been described as "melting snow".
"Have you drawn any conclusions on why NAC is able to treat cataract so
successfully? Is NAC breaking existing cross-links of proteins as well as inhibiting
them? Or are there other forces at work here too?"
Babizhayev: "The therapeutical indication for NAC to treat
senile cataract can lead to diminishing of light-scattering units in the lens,
probably by prevention of the oxidative modification of crystallins and utilization
of lipid peroxides that promote lens opacities.
biological antioxidants that can prevent oxidative damage to biological molecules
show some specificity in their mechanism of action, and so they can provide
only one type of protection. N-acetylcarnosine and its bioactivated analog L-carnosine
may exert their antioxidant properties by removing high reactive peroxide compounds
from the lipid phase of the lens, i.e. the fiber cellular membranes. We assume
the advantage of NAC is as a universal antioxidant, which relates to its ability
to give efficient protection against lipid peroxidation, both in the lipid phase
of biological membranes and in the aqueous environment. We maintain the hypothesis
that NAC assists the proprietary lens antioxidant systems including glutathione,
and the enzymatic antioxidant systems of the lens, to provide their operation
most effectively. Glutathione in conjunction with glutathione-related systems,
like glutathione reductase, can partially reduce the S-S bonds in the cross-linked
lens proteins. NAC can essentially prevent and reverse
the cross-linking of the lens proteins, including crystallins induced by lipid
hydroperoxides and their secondary breakdown molecular products, like aldehydes.
This mechanism can be prominent to reverse and prevent lens opacification that
is related to the glycation reactions of the lens proteins, and as you know
they are also associated with complications of diabetes."
"To-date what is the longest period that anyone has been continuing to
receive NAC eye-drops?"
Babizhayev: "Usually, we only provide well-controlled randomized
trials. Accordingly, we have no personal experience of clinical evaluations
lasting more than 2 years of therapy. We have always avoided any substance materials
that have originated from uncertain sources, so recently we developed the precise
cGMP manufacturing procedure for NAC."
"So are the benefits of NAC eye-drops being preserved in these long-term
Babizhayev: "Again, the total study period over 24 months
revealed that the beneficial effect of NAC is sustainable."
"I appreciate that your work has focused on the treatment of patients with
cataract, but do you envisage that NAC may also have a role to help prevent
Babizhayev: "Oh yes! We usually pursue the following therapeutical
strategy for the treatment of human cataracts with NAC. Firstly, we expect to
obtain the maximal effect of improvement of visual acuity within the first 3-5
months of therapy, then the clinical strategy is to maintain the received visual
outcome for a lasting period. In this connection,
NAC does indeed help to prevent human cataracts."
showing human cataract and normal human eye lenses.
is caused by the nuclear matter of the elderly human lens hardening and taking
on a yellowish/ brown color as shown here.
"Of course it has also been documented that L-carnosine, the sister to
NAC, is able to help prevent cross-links from occurring, yet I believe you do
not advocate L-carnosine as an eye-drop. Could you please explain to our readers
Babizhayev: "Topical administration of pure L-carnosine to
the eye does not lead to accumulation of this compound in the aqueous humor
within a reasonable amount of time, or in a concentration exceeding that of
the placebo-treated eye. Exogenous L-carnosine entering the organism topically
to the eye, intravenously, intraperitoneally, or with food is not accumulated
by the tissues, but is excreted or destroyed by carnosinase, a dipeptidase enzyme
that is present in blood plasma and in the aqueous humor of the anterior chamber
of the eye. With a topical eye application, L-carnosine releases the toxic compound,
histamine, which can severely promote oxidation reactions. Compared to L-carnosine
and due to its relative hydrophobicity, NAC appears to penetrate through the
cornea gradually, thus maintaining a longer active therapeutic concentration
of L-carnosine in the aqueous humor and the lens of the treated eye. Importantly,
NAC is highly resistant to hydrolysis by carnosinases. Different techniques
of ocular administration with NAC prove its efficacy for the treatment of cataracts,
combined with excellent tolerability to the eye, safety, and the lack of possible
showing the reduction of cataract in rabbit eyes.
picture: shows the cataract in the rabbit eye large in the center of
the eye, before treatment with n-acetylcarnosine eye drops.
picture: shows the cataract in the rabbit eye greatly diminished after
3 months of treatment with n-acetylcarnosine eye drops.
picture: shows the cataract even further diminished after 6 months
"Please allow me to recap. Your results indicate that
L-carnosine by itself when used as an eye-drop could be dangerous. However,
while some NAC eventually breaks down into L-carnosine, it does not cause any
side effects because it only breaks down into L-carnosine at a later stage;
which is at that point is not only, not dangerous but beneficial to the eye.
Is that basically correct?"
Babizhayev: "Yes that is correct. Specifically, L-carnosine
is first hydrolyzed with carnosinase and histamine and is released postponed
from its histidine moiety via the activity of histidine decarboxylases in tissues.
As the aqueous humor of the eye is a flow system, L-carnosine can be released
from the NAC ophthalmic vehicle in the eye and becomes active as an ophthalmic
antioxidant. L-Carnosine released in situ from its ophthalmic pro-drug NAC enters
the lens, which is not equipped with carnosinase activity and concurrently L-carnosine
is washed out with the aqueous humor flow, this then allows the chronical application
of NAC for the treatment of human cataracts over years." clinical
"I also understand that you have acquired the proprietary process of producing
a high-purity NAC for eye-drop use. Did you find that normal production of NAC
was in some way inferior?"
Babizhayev: "Thank you for this important question. The application
of NAC for the treatment of cataracts has been protected by the PCT patents
by our group."
are as follows: Babizhayev MA, Bozzo Costa E. Composizioni farmaceutiche contenenti
N-acetilcarnosina per il trattamento della cataratta. Italian Patent A61K gruppo37/00
20122 MI, Priority 15.10.1993 and Babizhayev MA, Bozzo Costa, E. Pharmaceutical
compositions containing N-acetylcarnosine for the treatment of cataract. Patent
PCT/EP 94/03340 SCB 238 PCT, 10.10.1994].
we advise competitors not to rush forward. There are many carnosines with little
or abandoned biological activities. This strongly varies with the content of
transition metals in the peptide moiety, admixtures of hydrazine and other impurities
dependent to the type of obtention and/or synthesis. We have developed the cGMP
manufacturing process for NAC which demonstrates its extraordinary biological
anti-cataract activity in humans. We have provided the chemical-functional correlation
of the NAC properties and ensured the clinical anti-cataract efficacy of the
product for human lenses. But if NAC is extremely pure this also abandons the
antioxidant and biological activities of the peptide product. Innovative Vision
Products, Inc., of Delaware, keeps proprietary the processing and permanent
biological and analytical controls, in order to manufacture the effective anti-cataract
NAC bulk material. This technology has been envisaged by cooperation and extensive
studies with a Japanese manufacturing facility."
"This is obviously an important breakthrough in anti-aging medicine and
I can foresee numerous attempts to copy your innovation. How can patients be
sure that they are getting your particularly pure NAC eye-drops when purchasing
Babizhayev: "The label carries the following statement, "N-acetylcarnosine
patented by Innovative Vision Products" [Ed.- IVP]. If it does not state
that, it isn't our NAC formula and will either be ineffective or possibly
even dangerous for eye-use."
"I congratulate you Dr. Babizhayev on your incredibly important work. It
certainly appears that NAC eye-drops are a major contribution to the control
and indeed the eradication of cataract, which by itself is clearly an age-related
disorder. Do you believe that NAC may be useful for any other eye disorders?"
Babizhayev: "We think that further attention should be directed
to ophthalmic application of NAC to treat cataract, ophthalmic manifestations
of diabetes, ocular inflammation, primary open-angle glaucoma, and retinal disorders
which involve the pathological mechanisms associated with oxidative stress."
"I think this is one of the most exciting anti-aging products to emerge
in recent years and I believe it is a clear example of anti-aging medicine at
its best. I wish you all success with this project and your future projects."
"Will you come back and tell the readers of the Anti-Aging
Bulletin about any further developments and breakthroughs you have?"
Babizhayev: "Of course, my pleasure."
ALL INFORMATION IS EDUCATIONAL. IT DOES NOT, AND SHOULD NOT, REPLACE THE ADVICE
OF YOUR PHYSICIAN. Last Updated: Friday, Thursday April 5th, 2007