Difference between revisions of "Alopecia - Hair Loss"

Revision as of 04:27, 1 November 2007

Rationale

• "Medication for men plagued by hair loss has become a topic of interest in Japan since a drug company began marketing it at the end of last year." March 5th, 2006 – source

• "An increasing number of companies are apparently turning the Chinese fear of a bald spot into big bucks with some doing so well they are branching out into other countries." February 16, 2006 – [1]

"There is something in the air, or should we say in the hair, these days. Scientific research into hair loss remedies has never been more active or more exciting." June 7, 2006 - [2]

Introduction

Hair basics

• Hair is a complex and delicate part of the body.
• Keeping it healthy and beautiful is a challenge.
• Hair grows everywhere on the body with the exception of lips, eyelids, palms of the hands and soles of the feet.
• Hair is basically a form of skin.
• Hair is made up of a protein called keratin.
• Each shaft of hair is made of two or three inter-twined layers of keratin which grow from a follicle beneath the skin.
• Hair Structure - [3]
• Hair Cycle - [4]

What causes hair loss?

• Decrease in growth of hair
• Increase in shedding of hair
• Breakage of hair
• Conversion of thick terminal hairs to thin vellus hairs

Survey results from Japan

Both men and women lose hair for similar reasons. Hair loss in men is often more dramatic, and follows a specific pattern of loss, one of which has been termed “Male Pattern Baldness" or "Androgenetic Alopecia".

Types of alopecia

• Alopecia Areata (AA): Hair loss occurring in patches anywhere on the body.
• Alopecia Totalis (AT): Total loss of the hair on the scalp.
• Alopecia Universalis (AU): Total loss of all hair on the body.
• Alopecia Barbae: Loss of facial hair (for a man) especially in the beard area.
• Alopecia Mucinosa: A type of alopecia which results in scaley patches.
• Androgenetic Alopecia (AGA): Also known as male pattern baldness. It is a thinning of the hair to an almost transparent state, in both men or women. It is thought to be a hereditary form of hair loss.
• Traction Alopecia: Traction alopecia is usually due to excessive pulling or tension on hair shafts as a result of certain hair styles. It is seen more often in women, particularly those of East Indian and Afro-Caribbean origin. Hair loss depends on the way the hair is being pulled. Prolonged traction alopecia can stop new hair follicles from developing and leads to permanent hair loss.
• Anagen Effluvium: This hair loss is generally caused by chemicals such as those used to treat cancer. Initially it causes patchy hair loss, which often then leads to total hair loss. The good news is that when you stop using these chemicals the hair normally grows back (usually about 6 months later). Other drugs also can cause hair loss. Many medicines used to treat even common diseases can cause hair loss.
• Scarring Alopecia: A form of alopecia which leaves scarring on the area of hair loss.
• Telogen Effluvium: A form of hair loss where more than normal numbers of hair fall out. There is a general 'thinning' of the hair. Unlike some other hair and scalp conditions, it is temporary and the hair growth usually recovers. (Source)

Androgenetic alopecia

• Gradual onset
• Transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, non-pigmented vellus hairs in the involved areas
• Characterized by a receding hairline and/or hair loss on the top of the head

Main causes

• Genetic predisposition
• Hormonal effect of androgen
• Reduction of blood circulation around hair follicle
• Deactivation of hair matrix cells

Some facts from Japan

• Market size: ¥ 30 Billion
• Number of products: more than 100

(JICST-EPlus - Japanese Science & Technology)

IP activity over the years

The graph indicates:

• Number of patents filed every 5 years (except for first 7 years).
• First solution proposed in 1973
• Filing trend indicates steep rise in activity recently.

IP Activity over years

Major players

Assignees with more than 20 patents

Assignees with fewer than 20 patents

• Active assignees

Assignees currently active with more than 5 patents to their credit during 2000-2005.

• Warner with 9 patents,
• Bristol with 6 and
• Abbott with 5.

Active Assignees

Treatment Approaches

Composition of treatment for causes are identified and categorized as follows:

• Anti-androgens (Finasteride) source
• Vasodilators (Minoxidil) source
• Double action (Anti-androgen + Vasodilator)
• Hair matrix cells activator

Anti-androgens

• Anti-androgens are used in hormone therapy.
• Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect leading to hair loss.

What causes hair loss?

• Testosterone is reduced to its active metabolite, Dihydrotestosterone (DHT) by the enzyme 5 alpha reductase.
• DHT attaches to androgen receptor sites at the hair follicle.
• DHT causes gradual miniaturization of the follicle, which eventually results in hair loss.

How do anti-androgens treat hair loss?

• Anti-androgens compete with DHT to bind to the androgen receptor.
• Upon binding of anti-androgen in place of DHT, follicle miniaturization is lowered and hair loss prevented.

Functions of Anti-androgen

Anti-androgen

Functions of Anti-androgen

IP Map for anti-androgen

Minoxidil (Vasodilators)

• Minoxidil is a "potassium channel opener" that leads to vasodilation.
• The drug is available in two forms. Oral minoxidil is used to treat high blood pressure and the topical solution form is used to treat hair loss and baldness.

What causes hair loss?

• A thick network of tiny veins and arteries line the outer wall of the follicle. Blood pumps through the bulb and hair via this network.
• DHT accumulates in the hair follicles and roots, constricting the blood supply of oxygen and nutrients to the hair roots; which is also seen to possibly contribute towards hair loss.

How does Minoxidil treat hair loss?

• Minoxidil is applied to the scalp topically, where it dilates blood vessels in the scalp and sustains the hair follicles for longer period of time.
• Minoxidil is thought to have a direct mitogenic effect on epidermal cells, as has been observed both in vitro and in vivo. Though the mechanism of its action for causing cell proliferation is not very clear, minoxidil is thought to prevent intracellular calcium entry. Calcium normally enhances epidermal growth factors to inhibit hair growth, and Minoxidil by getting converted to minoxidil sulfate acts as a potassium channel agonist and enhances potassium ion permeability to prevent calcium ions from entering into cells. (Source)
• Minoxidil sulfate (MS) appears to be the active metabolite responsible for hair growth stimulation.

Functions of Vasodilators

Functions of Monoxidil source

IP Map for Vasodilators

Double action (Anti-androgen + Vasodilator)

• Combination of Vasodilator + Anti-androgen (double action) composition for effective treatment of Male-Pattern Baldness.

What is the problem with using only Anti-androgen therapy?

• Anti-androgen is not effective in addressing the issue of vasocontriction around hair follicles due to sebum oil build up.
• Anti-androgen only prevents binding of DHT to androgen receptors. However, the effects of improper oxygen and nutrient supply to the brain due to vasocontriction still remains and gradually causes hair loss.

What is the problem with using only Vasodilator (or Minoxidil only) therapy?

• Vasodilator or Minoxidil-based products are generally not effective in stopping hair loss as vasodilators (or Minoxidil) do not block the harmful effects of DHT in the scalp and hair follicles.
• Vasodilators or Minoxidil simply dilate blood vessels in the scalp. However, the harmful DHT still gets produced in the body, enters the scalp and hair follicles causing hair loss.

How is the combination of Anti-androgens and Vasodilator (or Minoxidil) effective?

• Anti-androgens target the problem of DHT binding to androgen receptors and prevents follicle miniaturization.
• Vasodilators like Minoxidil cause vasodilation and therefore improve supply of oxygen and nutrients to the hair follicle and roots.
• Combination therapy therefore proves to be much more effective than individual therapy.

Functions of (Anti-androgen + Vasodilators)

Anti-androgen and Minoxidil

Functions of (Anti-androgen + Vasodilators)

IP Map for (Anti-androgen + Vasodilators)

Hair matrix cell activator

Hair matrix cell activator is a substance that acts at the matrix cells in the hair follicle preventing their degradation.

What causes hair loss?

• Stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge.
• Stem cells migrate to hair matrix where they start to divide and differentiate, under the influence of substances produced by cells of the dermal papilla.
• Perifollicular matrix cells undergo slow degradation which prevents follicle stimulation.
• Hair follicle activation is required for hair growth and thus inhibition of follicle activation eventually leads to hair loss.

How does hair cell matrix activator treat hair loss?

• Hair cell matrix activator slows down and inhibits degradation of the perifollicular matrix.
• This leads to an increase in hair follicle matrix cells that differentiate from progenitor stem cells.
• Matrix activator allows activation of hair matrix cells and therefore follicle stimulation leading to hair growth.

Functions of Hair matrix cell activator

Hair matrix cell activator

Functions of Hair matrix cell activator

IP Map for Hair matrix cell activator

Technology mapping based on patents analyzed

IPMap: Composition nature matrix

Focus of patents

Technology focus

Technology focus