Discovery of novel skin hypo-/hyperpigmentation active molecules

Achievements at Scientis Pharma have resulted in the breakthrough discovery of novel skin re- and depigmentation active ingredients :

  • Pyridines (picolinamide)
  • Thiols (odorless cysteamine)
  • Azoles (methimazole)
  • Hydrazides (isonicotinic acid hydrazide)

Discovery projects at Scientis Pharma are focused on three fields:

  • New melanogenesis inhibitors and inducers. Novel active molecules to serve as skin hypo- and hyperpigmentation treatment;
  • New melanocytotoxic molecules. Novel active molecules to serve as anti-melanoma agents;
  • Diagnostic and therapeutic devices in the field of dermatology and skin pigmentation.

by Dr. Ferial Fanian, MD Dermatology, Research and Development 

Clinical management of patients with pigmentary conditions

Patients with skin pigmentary conditions can visit our dermatologists at Scientis Dermatology Center, Geneva, Switzerland, specialized in the management of skin pigmentary diseases such as vitiligo or melasma.

by Dr Behrooz Kasraee, MD Dermatology, CEO

Hyperpigmentation: Melasma

Melasma can be epidermal, dermal or mixed.  Epidermal melasma is brownish in colour and results from an excessive amount of pigment in the superficial part of the skin, the epidermis.  Dermal melasma is rather grayish in colour. In this type, melanin pigments are also present in the deep part of the skin, i.e.  in the dermis. The mixed type melasma has both epidermal and dermal components.

Melasma is a hyperpigmentation disorder that results from the hyperactivity of melanocytes. Although it is also called the mask of pregnancy, many melasma patients develop this skin disease without any relation to pregnancy and the disease also exists in men.  Contraceptive pills, sun exposure and certain medications such as phenytoin can induce melasma, however, in most cases, the cause of melasma remains uncertain.

The treatment of melasma is principally based on the application of skin depigmentation products.  Several depigmenting molecules have been used for the treatment of melasma. The most effective treatments have been based on products that contain hydroquinone. Hydroquinone, after being applied onto the skin, is absorbed by the melanocytes and is metabolized within the (hyper-functioning) melanocytes to produce a toxic radical (quinone) that causes the abnormal melanocyte to die.  This causes the melasma area to become normal in colour, as hydroquinone has little or no effect on the normally functioning melanocytes.

Although hydroquinone is considered to be the most effective treatment for hyperpigmentation, its use has become more and more restricted in recent years due to reports on the cancer-producing effect of this agent. Hydroquinone has thus been banned in several countries including Europeen countries and Japan.

After hydroquinone ban, several products have been developed and put on the market for hyperpigmentation treatment. These products contain depigmenting agents such as kojic acid, azelaic acid, arbutin, glabridin, and more recently developed molecules as 4-butyl resorcinol or 4-ethyl-phenyl resorcinol.  However, experience has shown that the majority of these molecules and fractional laser treatments are far less effective than hydroquinone for the treatment of hyperpigmentation. The research for finding a new depigmentation therapy that can truly replace hydroquinone does continue.

Five decades ago, a group of researchers led by Dr. Chavin discovered a very potent depigmenting agent called Cysteamine. Cysteamine is a natural product present in minute concentrations  in human body cells as well as in human milk. These researchers found that the injection of Cysteamine into the black goldfish skin causes its skin to turn white. Later, other researchers such as Dr. Pathak and Dr. Bleehen confirmed the efficacy of topical Cysteamine as a depigmentation therapy and Dr. Pathak showed that Cysteamine cream was significantly more effecive than hydroquinone cream in producing skin depigmentation. However, all efforts for making cysteamine into a cosmetic cream for human use failed at that time. The reason was that cysteamine produced a very unpleasant odor when made into a cream. The odor, described as « skunk odor», could not be covered by any perfumes and thus the idea of making cystemaine into a cream was finally  abondoned despite its high efficacy and safety profiles.

Fifty years later, in October 2010, a young researcher using cysteamine in his research laboratory had an amazing accidental finding. He found that one of the cysteamine solutions he had prepared through combination of cysteamine with certain substances, had become odorless.

The odor-less cysteamine solution was later tested to verify if it had any skin depigmentation activity. Surprisingly, the comparison of the odor-less cysteamine product with the mal-odorous one, showed the same skin depigmenting efficacy for both products. Cysteamine cream that became utilisable as such, showed considerable skin depigmenting efficacy in human and was developed for the first time by Scientis pharma company as a new skin depigmentation product.  Scientis Pharma is the sole company in the wotld that has access to the technology of developing odor-less cysteamine cream.

Hypo-pigmentation: Vitiligo

Vitiligo is a skin disease that causes white patchy areas on the skin.

Human skin color is principally determined by the amount of a pigment called melanin present in the skin. Melanin is produced by specialized skin cells which are called melanocytes. Melanocytes are also present in hair follicules and are thus responsible for giving colour  to human hair.

White blood cells are responsible for protecting our body against infectious agents such as bacteria and viruses. However, sometimes our white blood cells can make a mistake in distinguishing our own body cells from infectious agents. In this case white blood cells might attack some of our own body cells and destroy them.  Diseases which are produced through such a mechanism are called « auto-immune diseases ».  Some auto-immune diseases include diabetes type II (where white blood cells attack and destroy the insulin producing cells of pancreas), or a type of hair loss that is called alopecia areata, where white blood cells attack and destroy the hair follicles.

In the case of vitiligo, white blood cells attack and destroy the pigment producing cells of the skin, melanocytes.  Since melanin pigment is no more produced in these areas of the skin, the skin becomes white in the areas where melanocytes are destroyed. Although vitiligo is responsible for important cosmetic (and thus emotional) disturbances, it is a benign disease and does not cause any serious health problems.

Complete and permanent cure is quite frequent through current treatments. The treatment of vitiligo has dramatically advanced during the past decade. The notion that « vitiligo can not be cured » is no more the case.

The treatment of vitiligo has two phases :

  • Blocking the white blood cells that attack and destroy melanocytes: this stops the progression of the disease.
  • Regenerating the destroyed melanocytes: this repigments the white patches.

Blocking white blood cells that attack melanocytes:

Non-cortisone topical creams have become available since about a decade ago and permit us to effectively block the white blood cells that are responsible for melanocyte destruction.  Tacrolimus and pimecrolimus are the two active ingredients used in such topical medications (Protopic and Elidel creams contain tacrolimus and pimecrolimus respectively).
These creams are applied daily on the depigmented (white) patches and block the white blood cells that kill melanocytes. Although this is an essential part for the treatment of vitiligo, this phase would only stop the progression of the lesions. The second phase of the treatment mentioned below is necessary to repigment the skin.

Regenerating the destroyed melanocytes

In general, the process of « repair » in our body occurs through the division of non-damaged cells and the migration of thus newly generated cells to the damaged areas.  In the case of melanocytes, such cell division and migration is hardly spontaneous and must be assisted by special treatments.
Norrow-band UVB treatment is a type of phototherapy that causes the non-damaged melanocytes to divide,  migrate and populate the vitiligo patches. These melanocytes then begin to produce melanin to repigment vitiligo areas. A type of laser called Excimer laser that emits narrow-band UVB light with a higher flow than the UVB lamps is currently used and is believed to be more effective than conventional UVB lamps.
It should be noted that, for an unknown reason,  only hair follicule melanocytes have the capacity to divide and migrate to vitiligo patches. That is why the presence of (pigmented) hair in the vitiligo patches is a determining factor for the response to narrow band UVB treatment. That is why areas of the skin which are completely devoid of hair (lips, palm of the hands and the distal part of fingers and toes) do not respond to UVB. It should be noted that, although not always visible by naked eyes,  most areas of our skin are covered by pilous hair  (fine soft hair) which are enough to repigment vitiligo after UVB stimulation.

The two treatment phases should be performed at the same time

This is a very important point. Without UVB, the creams (Protopic or Elidel) are not effective for repigmentation of vitiligo, as it is UVB that causes melanocyte regeneration. On the other hand, melanocytes regenerated by UVB would be readily destroyed by white blood cells if these creams are not used at the same time.  Both treatments should be done during the same period to produce successful vitiligo repigmentation.

Recalcitrant vitiligo

The above mentioned method has a very high efficacy on facial vitiligo and complete response is frequently seen. However, the efficacy of this method in much less on the vitiligo patches on the hands and the feet. Lack of response to treatment is also seen in vitiligo patches on the non-hairy areas of the body as well as vitiligo patches with white hairs.  Other methods such as melanocyte implantation can be used for the treatment of recalcitrant vitiligo lesions. In this method melanocytes are obtained from a biopsy performed on the normal skin and are then implanted to the vitiligo lesions. In newer methods melanocytes are obtained from the scalp hair before being implanted.
A new treatment option with Erbium laser associated with a medication called 5-FU has been recently reported to be successful in repigmenting recalcitrant hand vitiligo.

Depigmentation therapy

In the case of extensive vitiligo (vitiligo covering more than 50% of the body surface area), a treatment option is to whiten the normallly pigmented skin areas to obtain a « uniform » and permanent white skin colour. This is done through the daily application of a cream called Benoquin (containing 20% monobenzylether of hydroquinone). This treatment usually results in very satisfactory cosmetic results which are obtained after a few months of treatment. The colour of body hairs remain completely normal with this treatment and the patient appearance would be that of individuals with a natural white ethnicity.

Scientis experts practice all the newest methods in the world for vitiligo treatment.  Some of these methods include different Laser modalities, different melanocyte implantation methods, combination therapies and depigmentation therapy of extensive vitiligo.