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Journal of Dermatological Treatment
ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: https://www.tandfonline.com/loi/ijdt20
Randomized controlled trial on a PRP-like
cosmetic, biomimetic peptides based, for the
treatment of alopecia areata
Fabio Rinaldi, Barbara Marzani, Daniela Pinto & Elisabetta Sorbellini
To cite this article: Fabio Rinaldi, Barbara Marzani, Daniela Pinto & Elisabetta Sorbellini (2018):
Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based, for the treatment
of alopecia areata, Journal of Dermatological Treatment, DOI: 10.1080/09546634.2018.1544405
To link to this article: https://doi.org/10.1080/09546634.2018.1544405
© 2019 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group.
Accepted author version posted online: 04
Dec 2018.
Published online: 03 Feb 2019.
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RESEARCH-ARTICLE
Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based,
for the treatment of alopecia areata
Fabio Rinaldi, Barbara Marzani, Daniela Pinto and Elisabetta Sorbellini
International Hair Research Foundation, Milan, Italy
ABSTRACT
Background: Alopecia areata (AA) is a non-scarring auto-immune hair disorder. Recent researches
explained the role of growth factors (GFs) in hair follicle cycling. The main reservoir of GFs are alpha-gran-
ules of platelets and novel procedures have been implemented aimed at collecting platelet-rich plasma
(PRP). PRP has been safely implemented in many medical applications and has also been successfully
used as alternative cell-based therapy for the treatment of hair growth disorders, among which also AA.
Objectives: By means of a randomized double-blinded, placebo and active-controlled, parallel group
study we have studied the efficacy of a cosmetic product (named TR-M-PRP plus) comprising biomimetic
peptides specific for hair growth, mimicking PRP composition for the treatment of AA. Subjects were
treated for three months and evaluated, at the end of the study and after one month of follow-up, as
regards hair growth using SALT score.
Results: TR-M-PRP plus-like topic produced a statistically significant (p<.001) clinical improvement in
SALT score after 3 months of therapy, compared to baseline. Hair growth results further improved after
1 month of follow-up.
Conclusions: This clinical investigation suggests that the biotechnological designed PRP-like cosmetic
could represent a valid and safer alternative to autologous PRP for the treatment of AA.
Abbreviations: PRP: Platelet-rich plasma; ; AGA: Androgenetic alopecia; ; AA: Alopecia areata; GFs: growth
factors; VEGF: vascular endothelial growth factor; EGF: epidermal growth factor; FGF: fibroblast growth
factor; IGF: insulin-like growth factor; ADP: Adenosine diphosphate; SALT: Severity of Alopecia Tool;
bFGFs: Basic Fibroblast Growth Factor
ARTICLE HISTORY
Received 13 August 2018
Accepted 27 October 2018
KEYWORDS
PRP; biomimetic peptides;
alopecia areata; AA
What’s already known about this topic?
Platelet-rich plasma (PRP) PRP has been successfully used as
alternative cell-based therapies for the treatment of hair
growth disorder such as Androgenetic alopecia (AGA) or
Alopecia areata (AA).
What does this study add?
We have studied a topical formulation (named TR-M-PRP
plus) comprising biomimetic peptides specific for hair growth
mimicking PRP composition.
The results obtained with the present clinical investigation
suggest that the biotechnological designed PRP-like cosmetic
we investigated could represent a valid and safer alternative
to autologous PRP for the treatment of AA.
Introduction
Alopecia areata (AA), is a non-scarring auto-immune hair disorder
(1,2). Even though AA ethiology is not completely understood,
many clinical evidence suggested a role of immunity in the devel-
opment of such disease (3–5). Therefore, genetic predisposition,
environmental factor, psychological stress, hormonal unbalance,
concomitance with other skin disorders and gut dysbiosis can
contribute to autoimmune mechanism of AA (1,6,7). More
recently, a role of scalp microbiome has also been hypothesized
(8). AA is the second most common type of alopecia with an inci-
dence higher than 2% and a lifetime risk of 1.7% both in men
and women (9).
Currently, available treatment options for AA included: topical
(10), intra-lesional (11) or systemic (12) steroids, and immunother-
apy or systemic immuno-modulators.
Recent researches (13–16) explained the role of growth factors
(GFs), especially polypeptide in the life-long cyclic transformation of
the hair follicle, and their activity in control of immune privilege (in
particular IGF-1) (17). GFs act by stimulating cell proliferation and
differentiation and inhibiting apoptosis on dermal papilla cells and
stimulate stem cells of bulge area (18–20). This activity will result in
anagen prolongation and catagen delaying (21,22).
The main reservoir of growth factors in the body are alpha-
granules of platelets (23) and growth factors involved on hair fol-
licle cycling are mainly vascular endothelial growth factor (VEGF)
(24) epidermal growth factor (EGF) (25), fibroblast growth factor
(26,27) and insulin-like growth factor (IGF) (28). Adenosine diphos-
phate (ADP), serotonin and calcium are also released from dense
granules and are important in the recruitment of new platelets
and coagulation cascade (29).
Fabio Rinaldi fabio.rinaldi@studiorinaldi.com International Hair Research Foundation, Viale BiancaMaria 19, Milano 20122, Italy.
ß2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in
any way.
JOURNAL OF DERMATOLOGICAL TREATMENT
https://doi.org/10.1080/09546634.2018.1544405
Novel procedures have been implemented aimed at collecting
platelet-rich plasma (PRP) (30–34) releasing growth factors after
platelets degranulation (29).
PRP derived from autologous blood has a 1,000,000/UL plate-
lets concentration, which is 3–8 folds higher than normal periph-
eral blood (range 150,000–350,000 UL) (35,36).
First used in 1987 by Ferrari et al. (37) in transfusion proced-
ure, PRP has then been safely implemented in many application
fields, such as orthopedics and sports medicine, dentistry, neuro-
surgery, ophthalmology, urology, and wound healing (38,39). PRP
has also been successfully used as alternative cell-based therapies
for the treatment of hair growth disorder such as AGA (36,40)or
AA (41,42).
In a randomized, double-blind, placebo and active-controlled,
a half-head study on AA subjects, Trink and collaborators investi-
gated, for the first time, the safety and efficacy of PRP on hair
regrowth and dystrophy, burning or itching (43).
During the time, attempts have been made to standardize pro-
cedures for PRP preparation in order to reduce variation in the con-
centration of platelets and differences in manufacturing procedures
(44). With a view to the above limitations, the use of biomimetic
peptides, mimicking growth factors normally encountered in PRP,
could represents a valid alternative. They can be implemented in
an topical formulation and used for the treatment many conditions
in which modulation by growth factors is involved.
Normally, a biomimetic peptide is an oligopeptide (10–15 aa)
that provides similar efficacy of natural or recombinant growth
factors but reduce cost and owns more stability. By mean of bio-
technological development, a wide range of biomimetic peptides
has been developed since the beginning of 2000. Since their
birth, these novel discovered molecules represented a very prom-
ising application with regard to skin and dermatological applica-
tions (45). Several kinds of biomimetic peptides are currently
available on the market. They include signal peptides (46,47), car-
rier peptides (48,49) and also specific peptides targeting hair such
as tripeptide-copper complex (50), 5-aminolevulinic acid-GHK
(ALAVAX) (51) Octapeptide-2 (52,53), Decapeptide P3 (54) and Sh-
polypeptide 9 (55). In a previous randomized trial on 40 women
affected by chronic telogen effluvium, we have evaluated the effi-
cacy of a pool of selected mimicking growth factors (IGF 10%,
EGF 10%), included in a topical formulation, in preventing dermal
papilla apoptosis, prolong anagen phase and delaying catagen
and telogen (56).
More recently we have also evaluated in vitro the efficacy of a
mix of biomimetic peptides, the same used in the product cov-
ered by the present study, for hair growth stimulation (submitted
for publishing). Starting from the previously reported evidence we
have developed a cosmetic product (named TR-M-PRP plus) for
the treatment of AA, comprising biomimetic peptides specific for
hair growth and mimicking PRP composition.
Material and methods
Study design and patients
The study was structured in the form of a randomized double-
blinded, placebo and active-controlled, parallel group study. 60
subjects with AA of both sex, aged between 18–60 years, were
enrolled. For each AA patient, essential background data were col-
lected at baseline according to the guidelines of the National
Alopecia Areata Foundation (57,58). AA-grade was assessed accord-
ing to Severity of Alopecia Tool (SALT) (57) score (S0 ¼no hair loss;
S1 <25% hair loss; S2 ¼25%–49% hair loss; S3 ¼50%–74% hair
loss; S4 ¼75%–99% hair loss; and S5 ¼100% hair loss). Efficacy of
TR-M-PRP plus treatment was assessed as percentage hair regrowth
and the grading of overall improvement, calculated from change in
baseline SALT score. Absolute change in SALT score ¼SALT score
at baseline –SALT score at T2. Percentage of hair regrowth was
calculated as follows: 100 (Baseline SALT score SALT score at T1
or T2)/Baseline SALT score. Assessment of percentage hair regrowth
was graded into following 6 grades: A0 ¼no change or further loss
of hairs; A1 ¼1–24% regrowth; A2 ¼25–49% regrowth;
A3 ¼50–74% regrowth; A4 ¼75–99% regrowth; A5 ¼100%
regrowth. Subjects had also to accepting to not receive any other
drug/cosmetic treatments during the study and had not be
involved in a similar study during the previous 6 months. Exclusion
criteria included known sensitivity to any compound of the investi-
gational product, pregnancy or breastfeeding, any other medical
condition or other scalp or hair disorders.
All patients were evaluated and enrolled in the study by the RS
Dermatologic Clinic, Milan, Italy, after signed an informed consent.
The study was under the approval of the Ethical Independent
Committee for Clinical, not pharmacological investigation in
Genoa (Italy) and in accordance with the ethical standards of the
1964 Declaration of Helsinki.
Treatment
AA enrolled subjects were randomly divided into 2 groups: group I
included 30 AA patients treated with TR-M-PRP plus; group II
included 30 AA patients treated with Placebo. Both groups applied
the product twice a week (15 ml) for 3 months. Biomimetic peptides
used were: Copper Tripeptide-1, Octapeptide-2, Oligopeptide-20,
and Acetyl Decapeptide-3. Lactoferrin, lactoglobulin, and melatonin
were also included as an anti-inflammatory, ATP stimulator and cir-
cadian rhythm regulator agents, respectively.
Assessment of the response
Subjects have been visited three times: at the Randomization Visit
(Baseline T0), at the End of Treatment Period Visit at Month 3 (T1,
90 days), and at the Follow Up Visit, one month after treatment
end (T2, 120 days). Photography Digital photos were taken for the
scalp before therapy and during subsequent visits. Hair regrowth
in AA subjects has been evaluated using the SALT score which
expresses hair regrowth as a percentage from baseline (59–61). At
the end of the study (T1) and at the Follow up Visit (T2), each vol-
unteer has also filled out a questionnaire regarding the perceived
efficacy of the treatment and product compliance.
Statistical analysis
A two-sample Student’st-test was used for comparison at base-
line and during the study. p-values less than .05 were considered
clinically significant.
Results
A total of 60 subjects (37 men and 23 women) were enrolled and
received treatment (Table1). The TR-M-PRP plus-treated group and
Table 1. Subjects demographic characteristics.
Demographic AA
N¼60
Men (n, %) 37 (61.67 %)
Women (n, %) 23 (38.33%)
Age (y, mean ± DS) 54.32 ± 8.17
2 F. RINALDI ET AL.
placebo group had comparable baseline demographics and dis-
ease characteristics.
Hair-growth measured after 3 months of treatment and a fol-
low up of one month with TR-M-PRP plus (Group I) were com-
pared with values registered at the baseline and compared to
Placebo group (Group II).
Enrolled AA subjects presented a mean of 4.35 symmetrically
distributed patches of hair loss and had the last relapse 1–2 years
before (mean 1.2). They were no responsive to any other previous
treatment including systemic and topical immunosuppressant
therapies and phototherapy. Therefore, they received no treat-
ment for at least one year.
Absolute change in the baseline SALT score was calculated.
Mean value of the absolute change in SALT score was 18.30 and
8.49 for Group I and II, respectively. Percentage scalp hair
regrowth was derived from the absolute change in the baseline
SALT score for all the patients. After three months of treatment
(T1) the mean values were 57.07% for Group I and 27.96% for
Group II (Table 2). At T2 a further significative (p<.0001) improve-
ment was found for Group I (68.12% vs 28.89% in Group II).
In Group I, 53.33% cases showed complete regression (A5
grade) (Table 3). A partial regression was also seen in 13.33% of
population of Group I, but we did not consider that result as rele-
vant for the present study. 33.34% of subjects from Group I
showed no response at all (Table 3). Only 3.33% of population of
Group II reported a complete regression (Table 3).
No adverse effects were reported after TR-M-PRP plus or
Placebo administration. Therefore, all patients under investigation
reported a good compliance of the tested product.
Explicative photographic images showing hair regrowth effect
of TR-M-PRP plus were reported in Figure 1.
Discussion
The prevalence of hair loss in the population and its impact on
self-esteem and depression (62,63) poses the need of therapies
targeted to reduce the appearance of thinning by delaying, arrest-
ing, or reversing hair growth disorder. The synthesis of biotechno-
logical compounds mimicking growth factors opens to novel
therapeutic approaches.
The clinical study presented in the current work showed the
efficacy of a PRP-like cosmetic product to stimulating hair growth
in patients affected by AA.
In this study, a total significant improvement of SALT score
was reported for all 30 subjects enrolled and treated with TR-M-
PRP plus. The results show significant changes in the objective
parameters tested to evaluate the effectiveness of the treatment.
Indeed, the results indicate that the application of biomimetic
peptides in patients with AA leads to a decrease in hair loss prob-
ably due to prolongation of the anagen phase (probably acting
on WNT/b-catenin pathways and via exosomes stimulation) and,
consequently, due to the reduction of the telogen phase and pos-
sibly, by immunological control.
Following our previous work (43) several published works have
been reported as regards efficacy of autologous PRP in AA
(64–69). The product under study represents the first biotechno-
logical designed PRP able to reproduce the efficacy of autologous
PRP. Many biomimetic peptides are currently available on the
market but few reported a well-characterized action on hair
growth. We settled up a mix of biomimetic peptides able
together to simulate autologous PRP but avoiding its intrinsic lim-
itations (cost, interpersonal variation, invasiveness of the proced-
ure, and reported side effects).
All subjects under investigation well tolerated the treatment
and no side effects were identified. Therefore, all used biomimetic
peptides are protected by micro-encapsulation to avoid pepti-
dases and proteases degradation and these results in higher sta-
bility. Tripeptide-1 (GHK) (Glycyl-l-histidyl-l-lysine) is a biomimetic
peptide that is physiologically released during inflammation and
wound healing process (48). This peptide shows a high affinity for
copper ions, forming a complex (70): Copper Tripeptide-1 (GHK-
Cu). It possesses a diverse multiplicity of actions being able to
activate many remodeling related processes. Indeed, GHK-Cu is a
powerful anti-inflammatory agent in wound-healing (71–74). It
also acts on metalloproteinases and on extracellular matrix pro-
teins (70,75–77) and also stimulates angiogenesis (71,78). Most
interesting GHK-Cu is able to counteract hair loss through the
stimulation of stem cells, increasing hair follicle size (79,80).
We implemented in the formulation also Octapeptide-2 (Thr-
Ala-Glu-Glu-His-Glu-Val-Met). It is a mimetic of thymosin-b4
growth factor, a well-known stimulator of hair growth that acts
on angiogenesis and promotes the migration of stem cells and
their progeny to the base of the follicle. It also stimulates differen-
tiation and extracellular matrix remodeling (53,54).
Acetyl Decapeptide-3 is a Basic Fibroblast Growth Factor
(bFGFs) biomimetic whom efficacy has been largely proven in
skin regeneration. As biomimetic of bFGFs, it is involved in normal
skin growth, healing and wound repair. Most interesting, bFGFs
have been shown to be involved in hair development (27,28).
Oligopeptide-20 (8H-Cys-Arg-Lys-Ile-Pro-Asn-Gly-Tyr-Asp-Thr-
Leu-OH) is another peptide involved in hair growth mechanisms.
It’s supposed to act as an enzyme inhibitor leading to an increase
of the synthesis of collagen and glycosaminoglycans. The involve-
ment of collagen, in particular, collagen IV in hair cycling has
been recently reported (81). Reduced levels of collagen had also
been related to hair follicle aging (82).
We can postulate that the above-reported oligo-peptides may
simulate together the efficacy of autologous PRP (43) acting by
promoting hair follicle growth probably via stimulation of cell pro-
liferation. Further in vitro experiment could help in confirming
mechanism behind their mechanism.
The cosmetic product investigated contained also: (i) lactofer-
rin that is a potent anti-inflammatory agent (83) for helping in
Table 2. Percentage changes in baseline SALT (Severity of Alopecia Tool) score in Group I and Group II patients (per-
centage scalp hair regrowth).
Percentage changes
in baseline SALT score
After 3 months
of treatment (T1)
After 1 months
of follow-up (T2)
Statistical analysis
T0 vs T1 T0 vs T2 T1 vs T2
Group I 57.07 ± 5.91 68.12 ± 5.97 <0.0001 <0.0001 <0.0001
Group II 27.96 ± 8.51 28.89 ± 8.35 0.060 0.6136 1.039
Table 3. Grading of overall improvement in Group I and II.
Overall improvement Group I Group II
A0 (no hair regrowth) 10 8
A1 (1–24%) 1 11
A2 (25–49%) 0 6
A3 (50–74%) 1 4
A4 (75–99%) 2 0
A5 (100%) 16 1
JOURNAL OF DERMATOLOGICAL TREATMENT 3
counteract inflammation mechanisms of AA; (ii) lactoglobulin
helpful for stimulating mitosis and ATP production (84); (iii) mela-
tonin for clock gene regulation (85), a process strictly involved in
hair growth regulation.
Conclusion
The results obtained in the present clinical investigation suggest
that the biotechnological designed PRP-like cosmetic we investi-
gated could represent a valid and safer alternative to autologous
PRP for the treatment of AA. Further in vitro and in vivo studies
may help into better underline the mechanism behind its efficacy.
Disclosure statement
R.F. and S.E. serve as a consultant for Giuliani S.p.A. P.D. and M.B.
are employed by Giuliani S.p.A.
Funding
This study was supported by Giuliani SpA.
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