Significance Of Gene Therapy In Psoriasis

Pande V.V.

The replacement gene therapy of a particular disease is powerful tool to treat a genetic disorder by giving patient functional gene in place of defective gene.  Primary  candidate  for  replacement  gene  therapy  are  hereditary  disease  like  Adenosine  Deaminase  (ADA)  deficiency. 

The  disorder  result  from  a  mutation  in gene  that  code  for  the  enzyme  ADA. Gene Therapy  has   proved  to  be  simpler  in  theory  than  it  is  in  practice.  Getting  replacement genes into appropriate  cells  inserting  them  into  proper  site  within  the  genome  of  those cells  and  getting  them  to  function  and  response  normal  physiological  signal.  This  results  into need  to  investigate  gene  to  treat  various  genetic  disorders.  We  can  get  sequence  of  gene  or  chromosome  searching  gene  responsible  for  the  particular  disease  and  blasting  gene  sequence  of  crude  drug  which  is  used  clinically  to  treat  that  particular  disease.  In  this  literature  the  Psoriasis  hereditary  disorder  is  considered  for  study  and  gene  sequence  of  Lithospermum  crude  drug  is  used.  After  alignment  of  gene  sequence  of  psoriasis  with  the  gene  sequence of  lithospermum  it  is  found  that  63%  score  index  is  obtained.  It  is  generally  consider  that  score  index  from  50% to 70%  is  good  for  gene  therapy  of  a  particular  disease.

Introduction:-

The ability to isolate and clone specific genes gives us the power to do far more than simply replace missing or dysfunctional proteins. Through gene therapy, we will be able to treat genetic disorders by giving patients functional genes in place of defective ones. Only certain inherited genetic disease are amenable to correction via replacement gene therapy. Primary candidates for replacement gene therapy are hereditary disease like adenosine deaminase (ADA) deficiency,or the “Bubble Boy” disease. This disorder results from a mutation in gene that codes for the enzyme ADA. When ADA is not produced, intracellular toxins build up an kill cells of the immune system. Successful gene therapy experiments have been conducted on children who suffer from ADA deficiency and systic fibrosis, another inherited genetic disorder¹. Gene therapy has proved to be simpler in theory than it is in practice. Our initial enthusiasm for the extraordinary promise of the replacement gene therapy has been tempered with a large dose of reality. Enormous technical barrier must overcome before replacement gene therapy can live up to its potential to cure inherited genetic disorder. Getting replacement genes into the appropriate cells, inserting them into the proper site within the genome of those cells, and getting them to function and response to normal physiological signals². Even though these technical impediments may have tempered ouroptimism for using replacement gene therapy for inherited genetic disorder, our enthusiasm for the potential of more transient gene therapy as a tool for treating other disease has grown. Leading scientist are investigating the use of briefly introduced genes as therapeutics for a variety of cancer, autoimmune disease, acquired immune deficiency syndrome (AIDS), haemophilia, and other diseases³.

Psoriasis: -

Psoriasis is a non-infectious, chronic inflammatory disease of the skin characterized by well-defined erythematous plaques with silvery scales, which have a prediction for the extensor surfaces and scalp, and by a chronic fluctuating course. Psoriasis is come at any age but it is unusual between the age of 5, the oldest record onset was in a patient aged 107. There appear to be two epidemiological pattern of psoriasis. The first shows an onset in the teenage and early adult years, such individuals frequently have a family history of psoriasis, in a second epidemiological grouping disease onset in an individual fifties or sixties, a family history is less common. The clinical course of psoriasis is very variable. As a general rule the earlier the age of onset and the more severe the initial presentation, the more severe the lifetime course of the disease ^{4, 5}.

Clinical features:

Stable plaque psoriasis:

This is the most common type. Individual lesions are well demarcated and range from a few millimeters to several centimeters in diameter. The lesion are red with dry silvery white scaling, whish may be obvious only after scraping the surface. The elbows, knees and lower back are commonly involved. Other site of predilection include :

Scalp:

scalp is involved in approximately 60% of patients with psoriasis. Temporary hair loss is not uncommon and rarely permanent focal hair loss may occur.

Nails:

Involvement of the nails is the common, with “thimble pitting”, onycholysis (separation of the nail from nail bed) and subungual hyperkeratosis.

Flexures:

Psoriasis involving the natal cleft, and submammary and an axillary folds is not scaly, but red, shiny and symmetrical.

Palms:

Psoriasis here is often difficult to recognize, as individual plaques may be poorly demarcated and barley erythematous. It is often impossible to differentiate between psoriasis and eczema of the palms⁶.

Signs and Symptoms:

Irregular patches from pinpoint size to several inches in diameter, circular in shape.,Painful fissures in scalp, reddish lesions covered with silvery scales., Palms and soles are also affected, Lesions are dry., A white powder sloughs off after washing and  drying., Persistent itching.,The affected part of skin become rough., Lesion spread.

Avoid these foods and behaviors:

Milk, curd, sugarcane products, new rice right after harvesting, fish, meat, too much salt in diet, acid fruits and foods, vinegar, too much oily foods and food preparations, raw radish, over eating, sleeping during the day especially right after meal. Withholding the natural urges, swimming right after sun bath

Recommended diet:

Barley whole-wheat bread, honey, eggs, brown rice, beans, orange, meat of kada a wild bird, green vegetables, sweet and astringent fruits(not sour), ghee, butter and cheese, boiled and filtered water to drink, tea, coffee, etc⁷.

Prevention of psoriasis :

¨ Cleanliness of hands, nails and washing hands after every work is must. Contamination of eatables with insects or rats should be taken care of and avoided.

¨ Incompatible foods e.g. milk taken together with fish or acidic food should be prohibited.

¨ Very heavy meal and opposite of it, hot drink right after cold drink and vice-versa (we could note usually that the people drink cold water after a cup of hot tea or coffee) is not good for the skin diseases ^9,10.

Treatment:

Treatment can be classified into four categories:

¨ Easily applied topical agents such as emollients, corticosteroids, vitamin D agonist or ‘weak’ tar or dithranal preparations.

¨ Ultraviolet therapies such as PUVA and ultraviolet B.

¨ Systemic agents such as retinoids or immunosuppressive such as cyclosporin.

¨ Intensive inpatient or day patients care with topical agents and ultraviolet radiation under medical supervision ^{11, 12}.

Lithospermum: -

The genus Lithospermum belonging to the family Boraginaceae contains plants with hormonal activity. The seeds of the European.L.officinale (groom well) were formely official in several pharmacopoeias. The reported constituents of the herbs are shikonin, a naphthoquinone derivative; scyllitol, a cyclitol; a cyanoglucosides lithospermoside; caffeic, chlorogenic and ellagic acids; and catechin-type tannins. Shikonin, the enantiomer of alkannin (found in Anchusa Root) is also a constituent of L.erythrorhizon root and is produced for the cosmetic and pharmaceutical industries in Japan by cell culture of the plant. The structure of an endogenously produced oligogalacturonide necessary for the induction of shikonin biosynthesis in the culture. For investigations relating to the biosynthesis of shikonin from P-hydrobenzoic acid and geranyl pyrophosphate in Lerythrorhizon.¹³

In the Far-East, preparations of the purple roots have long been used for the treatment of burns, inflammations, wounds and ulcers. In Europe, alkanna root has been similarly employed and it has now been shown in laboratory tests that Shikonin and alkannin have no significant difference in anti-inflammatory activity. The occurrence of these naphthoquinones is of interest, since similar compounds occur in the related families Rubiaceae (Galium, Rubia), Verbenaceae and Bignoniaceae. Lithospermum arvense is used as an oral contraceptive in central Europe, as it suppress the oestrus cycle. The North American Lithospermum ruderale has similar hormonal activity.

Disorders For Which Gene Therapy Is Being Tested: -

Brain tumors, Haemophilia, Liver cancer, Prostate cancer, Hemoglobin disorder, Hyperlipidemia, Metabolic storage disorders, AIDS, Colon cancer, Melanoma, Solid tumors, Graft vs., host in bone marrow transplant for leukemia Point mutations in bone marrow cells., Head and neck cancer., Asthma, Focal muscle atrophy., Graft vs. host disease, Breast and ovarian cancer, Cardiovascular disease, Non-small scale lung cancer, Hypercholesterolemia, Infectious disease Neurodegenerative disease^{5, 6, 7}

Application Of Bioinformatics14 : -

Nowadays, the biological data is available on computer by connecting our computer with

Internet opening the NCBI website. We can get the sequence of gene or chromosomes. We can search for genes responsible for particular disease and also gene available in plant or crude drugs. We also know that the particular crude drug is used to treat the particular disease for e.g. Vinca rosea is used in the treatment of cancer. This is clinically proved and we get the possible result. Similarly we also know that lithospermum is used in treatment of psoriasis. If we find out the genes sequences available in lithospermum using the science of Bioinformatics and also the gene responsible for psoriasis and if blasting is done in gene of psoriasis and lithospermum so we will get result of blasting and alignment (homology) of gene sequences which should be between 50% to 70%. If we get the alignment between this range that means the genes present in lithospermum can be used to treat psoriasis effectively. In this literature we have done blasting of gene of lithospermum with gene of psoriasis & the result of blast were found to be 63%. On the basis of available data we can extrapolate that Lithospermum can used in the treatment of Psoriasis.

Conclusion: -

From the above information and result obtained after the blast we can say that, the gene sequence of Lithospermum will be successful to treat the patient suffering from psoriasis.

References: -

1. Recombinant  DNA  and  Biotechnology  (A  guide  for  teachers)  by  Kreuzer  and  Massey., 2003; 112-115.
2. Recent Advances in Psoriasis: The Role of the Immune System by Barbara S Baker – Medical, 2000; 144.
3. Therapy of Moderate-To-Severe Psoriasis by Gerald D Weinstein, Alice B Gottlieb - Medical – 2003; 384.
4. Dermatologic Therapy in Current Practice by James G Marks, Ronald Marks, James J Leyden – Medical; 2001, 67.
5. Psoriasis Pocketbook by Griffiths, Christopher E.M., Kirby, Brian – 1999; 64.
6. Brief Therapy by Jeffrey K Zeig - Psychology 1990; 467.
7. The Future Factor: Forces Transforming Human Destiny by Michael G Zey - Social Science 2004; 51.
8. Dermatology at the Millennium by Delwyn Dyall-Smith, Robin Marks - Medical 1999; 802.
9. Clinical Trials of Genetic Therapy With Antisense DNA and DNA Vectors edited by Eric Wickstrom - Medical – 1998; 21.
10. Molecular Genetics and Gene Therapy of Cardiovascular Disease by Stephen C Mockrin -  Medical 1996;
11. Ayurved line  (cover story skin care, page no 30-33)
12. Pharmacognosy by Trease and W.C.Evans, 15^th Edition.
13. http//www.ncbi.nlm.nih.gov.

About Authors:

Pande V.V.

MAEERS, Maharashtra Institute of Pharmacy, Kothrud, Pune-38

Chandorkar J.G

Innovassynth Technologies Ltd. Khopoli.

Tekade A.R

Siddhant College of Pharmacy, Sudumbare, Pune.

Dubey Sonal

KLE’s College of Pharmacy, Rajajinagar, Bangalore-10.

Chandewar A.V.

P. Wadhwani College of Pharmacy, Girija Nagar, Yavatmal –445001.