Novel and Emerging Therapies Safeguarding Health of Humans and Their Companion Animals: A Review
Mohd. Yaqoob Wani,
Amit Kumar Verma,
Modern medicine has helped to a great extent to eradicate and cure several diseases of mankind and animals. But the existence of incurable diseases like cancer, Acquired Immunodeficiency Syndrome (AIDS), diabetes or rheumatoid arthritis, side effects of allopathic medicine, increasing trend of antibiotic resistance and chemicals and biopesticides causing dietary risk have made the situation more critical than ever before. Thus, it has become a matter of concern for the scientists and researchers to develop novel therapies. Bacteriophage therapy to treat pathogenic bacterial infections, virophage therapy for conservation of global system and avian egg yolk antibody therapy for designing prophylactic strategies against Gastrointestinal (GI) diseases are interesting approaches. Others include the use of cytokines as adjunctive immunomodulators, gene therapy focusing on diseases caused by single gene defects, RNAi technology to suppress specific gene of interest and apoptins for cancer treatment. Stem cell therapy against several diseases and ailments has also been discussed. The use of nanoparticles for better drug delivery, even though costly, has been given equal importance. Nevertheless, immunomodulation, be it through physiological, chemical or microbial products, or through essential micronutrients, probiotics, herbs or cow therapy prove to be cost-effective, causing minimum adverse reactions when compared to allopathy. Development in the field of molecular biology has created an enormous impact on vaccine development. The present review deals with all these novel and emerging therapies essential to safeguard the health of humans and companion animals.
to cite this article:
Kuldeep Dhama, Sandip Chakraborty, Mahima , Mohd. Yaqoob Wani, Amit Kumar Verma, Rajib Deb, Ruchi Tiwari and Sanjay Kapoor, 2013. Novel and Emerging Therapies Safeguarding Health of Humans and Their Companion Animals: A Review. Pakistan Journal of Biological Sciences, 16: 101-111.
Received: November 23, 2012;
Accepted: February 12, 2013;
Published: March 16, 2013
The state of underdevelopment can be studied in the limelight of its relation
with infectious diseases that has a negative impact on the production of industrial
goods and animal proteins, especially in underdeveloped countries (Astudillo
and Rosenberg, 1983). In this context, infectious diseases act as factors
contributing to the state of underdevelopment especially in country like India.
The impact of animal and poultry diseases like foot and mouth disease (Verma
et al., 2008a, 2012), brucellosis (Kumar
et al., 2009), mycoplasmosis (Kumar et al.,
2011, 2012a), chicken infectious anaemia (Dhama
et al., 2002; Bhatt et al., 2011)
is also very important, mostly because of animal health restrictions based on
these endemic diseases. Loss of health in pet animals due to diseases like canine
parvovirus (Singh et al., 2013), campylobacteriosis
(Kumar et al., 2012b, c),
salmonellosis (Verma et al., 2007), canine distemper
or Feline Infectious Peritonitis (FIP) hearts the sentiment of owners. Moreover,
the lethal diarrhoea caused by colibacillosis (Malik et
al., 2012), rota viruses, corona virus, the H5N1 avian influenza and
the zoonotic disease like campylobacteriosis, salmonellosis (Verma
et al., 2008b) rabies are quiet noteworthy in the context of safeguarding
public health (Dhama et al., 2005a; Brownlie
et al., 2006; Lambey et al., 2009;
Dhama et al., 2009; Pawaiya
et al., 2009; Singh et al., 2009;
Verma et al., 2011a, b;
Patyal et al., 2011; Hansa
et al., 2012; Deb et al., 2012).
Modern medicine has done much to eradicate and cure disease, but it has failed
in some areas due to the existence of incurable diseases like cancer, AIDS,
diabetes and rheumatoid arthritis. Cancer affects one in every three persons
born in developed countries and is a major cause of sickness and death throughout
the world and therapeutic approach is critical due to critical immune response
(Cavallo et al., 2011; Mahima
et al., 2012a). HIV infection and AIDS are disproportionately afflicting
Third World countries, where substantial adult communities and villages are
literally being annihilated as because there is no known cure for HIV/AIDS and
due to involvement of high costs of current antiviral therapy (Livingston,
1993). Similarly, therapeutic approaches against diabetes and rheumatoid
arthritis are critical (www.cimzia.com).
Long term life regimen of allopathic medicine has potential side effects. Uncontrolled
and inappropriate use of antibiotics that have promised much in elimination
of major diseases of humans and animals, result in resistance, critical for
the future of antimicrobials (Raghunath, 2008; Kumar
et al., 2012b; Taddele et al., 2012).
Systemic pesticides used in genetically modified crops like Bt corn, account
for 60% (approx.) of dietary risk in domestic crops, ultimately proving troublesome
to human health (Monosson, 2005).
Due to advancement in the field of science, field of molecular biology and
biotechnology along with nanotechnology are enriched which have led to the generation
of many novel therapies (Bartol et al., 1999;
Chakravarthi and Balaji, 2010; Shirley
et al., 2011). Therefore, the present review discusses these novel
technologies involving bacteriophage, virophage, avian egg antibody, cytokine,
gene, siRNA, apoptins, stem cells, nanomedicine, immune system, vaccines, probiotics
and herbs safeguarding human and animal health.
Bacteriophage therapy: Bacteriophages can be used for checking bacterial
contamination food materials, controlling water-borne infections and food-borne
pathogens and remarkably for a variety of severe infections. These are magical
viruses that kill bacteria by lysing them and are particularly very useful for
treating antibiotic-resistant infections in animals and humans (Tiwari
et al., 2012). Oral administration or topical application of phages
have been attempted for a wide range of bacterial infections, caused by wounds
or surgical intervention (Mathur et al., 2003;
Tiwari et al., 2011, 2012)
including inflammation of larynx, gums, teeth, sinuses, conjunctiva, infections
of skin, gastrointestinal tract, urinary tract, skin infections, burns, boils;
and interestingly, cocktailed against some bacteria viz., P. aeruginosa,
Staph. aureus and E. coli (Sulakvelidze
et al., 2001; Hanlon, 2007; Rhoads
et al., 2009; Lu and Koeris, 2011; Sulakvelidz,
2011). Bacteriophages can be particularly very effective in treating drug-resistant
bacterial infections in humans and animals including poultry. Therapeutic applications
include treating various bacterial infections, viz., E. coli, P. aeruginosa,
K. pneumoniae, S. aureus, S. pyogenes, Bacillus anthracis, Salmonella spp.,
Campylobaeter jejuni, C. coli, Listeria monocytogenes and others (Tiwari
et al., 2012).
Virophages: Virophages/satellite viruses depend on the coinfection of
their host by another virus inhibiting or damaging the reproduction of the auxiliary
virus, examples include Sputnik, Mavirus and Organic Lake phages (Krupovic
and Cvirkaite-Krupovic, 2011; Fischer, 2011; Fischer,
2012; Desnues et al., 2012). Sputnik can
have major effects on ocean nutrient cycles and climate and may play a crucial
role in conservation of global systems by regulating the host virus interaction,
carbon influx in organic lake, growth and death of planktons (La
Scola et al., 2008; Monier et al., 2008).
Yolk antibody therapy/avian egg antibody therapy: Now-a-days, there
is progress to use chicken egg as source of antibodies for the prevention and
treatment of gut associated infections (Michael et al.,
2010), wherein, after immunization, the specific antibodies, otherwise known
as IgY are transported to the egg yolk and they can then be separated without
sacrificing the bird. Oral administration of IgY has been tried and found useful
in treatment of man and animals against microbes including viruses like rotaviruses,
bovine coronavirus; bacteria like enterotoxigenic Escherichia coli, Campylobacter
jejuni, Yersinia ruckeri, Salmonella spp., Pseudomonas, Edwardsiella
tarda and Staphylococcus aureus (Mine and
Kovacs-Nolan, 2002; Kovacs-Nolan and Mine, 2004).
The Egg Yolk Antibody (EYA) therapy has also shown promising therapeutic results
in cases of infectious pathogens/diseases of poultry viz., infectious bursal
disease (IBD), New Castle disease (ND), avian influenza subtype H9N2, salmonellosis,
campylobacteriosis, and Pseudomonas aeruginosa, Salmonella enteritidis,
Staphylococcus aureus and Eimeria tenella or E. maxima (Yegani
and Korver, 2007; Rahimi et al., 2007; Da
Silva and Tambourgi, 2010; Dhama et al., 2011a).
Cytokine therapy: The cytokines are used as adjunctive immunomodulators
in a variety of infectious diseases (Hafler, 2007;
Dhama et al., 2008a). The classical examples
include the use of recombinant α-interferons and nucleoside analogs for
hepatitis B virus (HBV), pegylated interferons and ribavirin for hepatitis C
virus (HCV) (Forton and Karayiannis, 2006; Trapero-Marugan
et al., 2006), HIV-associated cryptococcal meningitis (Antachopoulos
and Roilides, 2005) and Crohns disease (Pizarro
and Cominelli, 2007). The immunoglobulin Fc fragment based cytokines provides
superior therapeutic approach (Jazayeri and Carroll, 2008).
Nevertheless, the development of new vaccines necessitates the development of
new types of adjuvants to ensure an appropriate immune response (Nicholls
et al., 2010), examples include the use of cytokines like IL-7, 12
and 15 as mucosal vaccine adjuvants, Granulocyte-macrophage Colony-stimulating
Factor (GM-CSF) along with Monocyte Chemotactic Proteins (MCPs) and Macrophage
Inflammatory Proteins (MIPs) to increase recruitment of blood-borne dendritic
cells and monocytes to interstitial sites of vaccine delivery etc.
Gene therapy: Gene therapy finds its application in various diseases
caused by single gene defect (Thalassemia, sickle cell anemia, cystic fibrosis,
haemophilia and muscular dystrophy). The various therapeutic approaches in this
context include somatic gene therapy, germ line therapy and use of both viral
and non-viral vectors. Transfection of the cell is achieved by electroporation,
gene gun, sonoporation, magnetofection, use of oligonucleotides, naked DNA injection,
lipoplexes, dendrimers and inorganic nanoparticles (Agha-Mohammadi
and Lotze, 2000; Goverdhana et al., 2005).
Gene therapy is used in case of lymphoma, retinitis pigmentosa, diabetes etc.,
(Woods et al., 2006; Cepko,
2012; Callejas et al., 2013).
siRNA therapy: Suppression of specific genes of interest by synthetic
dsRNA has made RNAi a valuable research tool. Short interfering RNA was easier
to introduce in comparison to long dsRNA strands into mammalian cells (Paddison
et al., 2002). This RNAi has been successfully used in treatment
of various viral infection like respiratory syncytial virus, herpes simplex
virus type 2 and measles infection. Apart from infectious diseases they are
also helpful in inhibiting virus induced cancerous growth, have receptor-knockdown
activity and plays role in gene silencing (Sah, 2006;
Jiang and Milner, 2002; Crowe,
2003; Kusov et al., 2006; Jia
et al., 2006; Li et al., 2006; Hu
et al., 2005; Raoul et al., 2006).
Apoptins: Drugs directed against defective apoptotic pathways (apoptins)
may act as a double-edged sword and forms an interesting target of cancer treatment
(Wong, 2011). Approaches for apoptin based therapy to
treat cancer include use of agents like oblimersen sodium Bcl-2 antisense oblimer,
oblimersen in myeloid leukaemia, use of mutant p53 in pancreatic cancer, silencing
of Bmi-1 in MCF breast cancer cells, use of XIAP antisense oligonucleotides
in lung cancer and transfection of anti-sense survivin in squamous cell carcinoma
(Rai et al., 2008; Morton
et al., 2010; Suzuki and Matsubara, 2011;
Ohnishi et al., 2006; Sharma
et al., 2005). Apart from that, chicken anaemia virus VP3 protein
is also used in treatment of cancer (Natesan et al.,
Stem cell therapy: Introduction of new adult stem cells into damaged
or injured tissue forms the basis of stem cell therapy (Lindvall
and Kokaia, 2006). Haematopoietic stem cell therapy is used for treating
cancer; other uses in human and veterinary medicine include treatment of neurological
damages viz. Parkinsons and Alzheimers disease, spinal cord injury,
treatment of equine tendinopathies, Crohns disease, heart damage, diabetes,
inhibiting acute pancreatitis, lung therapy, Acute Respiratory Distress Syndrome
(ARDS), corneal epithelial reconstruction etc (Androutsellis-Theotokis
et al., 2008; Cummings et al., 2005;
Centeno et al., 2008; Ribitsch
et al., 2010; Jiang et al., 2012;
Fryer et al., 2013; Wen et
al., 2013; Ardhanareeswaran and Mirotsou, 2013;
Cardenes et al., 2013; Menzel-Severing
et al., 2013). However, there are many barriers like biological,
technical and clinical that have to be crossed before using this therapy in
clinics (Ouyang and Yang, 2013).
Nanomedicines: Since 2000, there is boom of nanotechnology in science,
engineering, technology and even in society. This technology can be used in
medical and veterinary field for diagnosis, treatment, and prevention of various
diseases (Kato, 2013) especially through drug delivery,
imaging and vaccine adjuvant (Irache et al., 2011;
Underwood and van Eps, 2012). Nanomedicine forms the
application part of nanotechnology. The common nanomedicine vehicles are solid
drug nanoparticles, polymer-based carriers and nanoemulsions that can be used
for treatment of various infectious diseases including retroviruses (Siccardi
et al., 2013). Gold-conjugated nanoparticles improve the therapeutic
properties of drugs by selectively targeting certain organs based on their size
and charge (Minchin, 2008; Allen
and Cullis, 2004), especially anticancer agents. For example, use of carbon
nanoparticles (Hollmer, 2012) for paclitaxel or liposome
for doxorubicin (Garde, 2012); polymers and liposomes
for delivery of camptothecins and platinum (II) drugs (Kieler-Ferguson
et al., 2013) and so also use of polyethylene glycol for better delivery
of several antibiotics (Trafton, 2012).
Immunotherapy: The main objective of immunotherapy is to control an
immune response (Fraile et al., 2012). Use
of monoclonal antibodies is an interesting approach (Deb
et al., 2013), wherein, they are coupled with drugs (magic bullets)
(Nielsen et al., 1986). Other immunomodulators
include a diverse groups of physiological (neuroendocrine hormones and glucocorticoids,
neurotransmitters and neuropeptides, thymic products (Dan
and Lall, 1998; Singh et al., 1998; Wilckens
and De Rijk, 1997), microbial (heat killed or formaldehyde treated anaerobic
suspension of Propionibacterium acnes) (Becker et
al., 1989) and plant/herbal products (Mahima et
al., 2012a). Synthetic chemical compounds like levamisole, imuthiol,
avridine, biostim etc. are good immunomodulators (Coppel
and Kulkarni, 2012).
Therapeutic vaccines: Prevention of diseases by vaccination has been
an integral part of health management programs as this has successfully prevented
many important diseases in a cost-effective manner (e.g., inactivated vaccine
against warts in cattle) (Ferro and Mordini, 2004;
Singh et al., 2008; Pathania
et al., 2011). Molecular biology has created an enormous impact on
vaccine development, leading to development of DNA vaccines (targeted animal
diseases include FMD, tuberculosis, Brucellosis, Rabies, Canine distemper, Johnes
disease), subunit vaccine (against Infectious bovine rhinotracheitis and rabies),
anti-idiotypic and virosome vaccine, virus-based nanoparticles and virus like
particles, biotechnologically engineered vaccine against pseudorabies etc.,
(Dhama et al., 2008b; Mengeling
et al., 1997). Importantly, plant based oral vaccine have gained
popularity in human medicine and has been found to be protective against diseases
like Hepatitis B, Human Immunodeficiency Virus (HIV), Cholera, Tetanus, Malaria,
Measles, Japanese encephalitis (JE) and Influenza (Mercenier
et al., 2001; Daniell et al., 2009).
Design and development of therapeutic cancer vaccines has proven to be an enormous
challenge (Pejawar-Gaddy and Finn, 2008). But with
the development of whole tumour cell vaccines, as is tumor-derived Chaperone-rich
Cell Lysate (CRCL) vaccine, genetically modified tumor cell vaccines viz. immunizations
with canine tumor cell lines transfected with human GM-CSF, peptide vaccines
by using Wilms tumor gene, heat shock protein vaccine, dendritic cell
vaccine etc. (De Gruijl et al., 2008; Li
et al., 2008; Hogge et al., 1999;
Oka and Sugiyama, 2010; Blachere
and Srivastava, 1995; Adamson et al., 2009)
have made the management of wide variety of tumors easier than earlier.
Nutritional immunomodulation/therapy: Nutrition plays a pivotal role
in modulation of immunity and there must be adequate supply of nutrients for
the proper functioning of immune system. Nutritional deficiency affect immune
cells and inhibits vital functions,like the cytokine responses (Katona
and Katona-Apte, 2008) for which there is need to supply essential micronutrients
viz. Vitamins A, D, E, C, B6, folate, B12 (Ramakrishnan et
al., 2004; Veldman et al., 2000; Meydani
et al., 2005; Haertel et al., 2004;
Leklem, 2001; Dhur et al.,
1991; Tamura et al., 1999) and trace elements
viz. selenium, zinc, copper and iron (Chaudhary et al.
2010, Mahima et al., 2012b and Mahima
and Mudgal, 2012; Cuevas and Koyanagi, 2005; Bonham
et al., 2002; Openheimer, 2000) in the diet.
Leptin is considered as an emerging cytokine-like immune regulator found to
be effective in nutritional problems (Cunningham-Rundles
et al., 2005).
Probiotics: Probiotics (direct feed microbials) are naturally occurring
and selected beneficial live microorganisms that create a positive impact on
the physiological status of the host (Dhama and Singh, 2010).
Probiotics include bacteria, fungi and yeast that create an unfavourable atmosphere
for the pathogenic microbes in gastrointestinal tract (Bengmark,
1998). Generally, live apathogenic bacterial strains belonging to genus
Lactobacillus, Streptococcus or Enterococcus, are used
in livestock and poultry (Balevi et al., 2001;
Dhama et al., 2008c, 2011b.
Bacillus, Aspergillus, Saccharomyces and others are also being used.
Various studies have proved this for example increase in circulating antibody
secreting cells by Lactobacillus in diarrhoea (Kaila
et al., 1992) and enhancement of intestinal IgA production by Bifidobacterium
bifidum (Park et al., 2002) etc. Probiotics
have been found to enhance immunity and prevent various enteric infectious diseases
caused by bacterial, fungal, protozoan and viral agents. These have been proven
to be protective and combating various harmful pathogens viz. E. coli,
S. aureus, Salmonella spp., Clostridium perfringens, Listeria
monocytogenes, Campylobacter jejuni, Yersinia enterocolitica,
Candida albicans, coccidian parasites (Eimeria spp.) etc. (Dhama
et al., 2008c, 2011b). For best results,
a multi strain probiotic should be used timely.
Herbal therapy: Globally many researches are going on role of plants
and their extracts in enhancing the immunity of man and animals (Mahima
et al., 2012a). Historically, various plants have been used in traditional
system of India in the name of Rasayanas, which increases the resistance of
the body against various pathogens (Tan and Vanitha, 2004).
Various herbs viz., tulsi, ginger, chilli, turmeric, onion, garlic, spices,
coriander etc are traditionally used for the treatment of different ailments
based on Indian Traditional knowledge. Plants are source of phytochemicals that
can have anti-microbial, antiviral or antifungal and immunomodulating activities.
Some of the examples of medicinal plants are Tinospora cordifolia, Piper
sarmentosum, Glycyrrhiza species, Gymnema species, Centella asiatica,
Camellia sinensis, Crataegus species and Olea europaea, which
can be used for treating the chronic diseases viz., diabetes, blood pressure,
high cholesterol, rheumatoid arthritis etc (Mahima et
al., 2012a). Plants are also used for the treatment of many parasitic
diseases including malaria, toxoplasmosis, helminth infestations, chagas disease
etc. Vinca alkaloids (vinblastine and vincristine) from the Madagascar periwinkle,
(Catharanthus roseus G.); Paclitaxel from bark and other parts of Taxus
brevifolia, Taxus Canadensis and Taxus baccata; Camptothecin,
(from Camptotheca acuminate); Epipodophyllotoxin (from Podophyllum species)
and Homoharringtonine (from the Chinese tree Cephalotaxus harringtonia
var. Drupacea) have been used as anticancer drugs for treatment of ovarian cancer,
breast cancer and lung cancer. Fresh Allium sativum, called ajoene, appears
to protect CD8+ cells from attack by HIV, gives protection against human cytomegalovirus
(HCMV) in a dose dependent manner (Guo et al.,
1993) for example Piper longum has anti-tumour activity (Sunila
and Kuttan, 2004). The roots of Astragalus, Isatis and Achyranthes significantly
improve the immunity (Hashemi and Davoodi, 2012).
Cow therapy: The concept of cow therapy is based on the use of five
constituents viz., milk, curd, ghee, urine and dung extract obtained from Indian
Zebu cow, thus also known as Panchagavya (Verma, 2005).
Panchagavya plays an important role in Ayurveda system of medicine and has got
mention in ancient Indian literature as it enhances the body resistance and
refractoriness to infections (Dhama et al., 2005b).
Panchagavya/cowpathy has been reported to be useful for the treatment of several
disorders and diseases like allergies, colds, cough, renal disorders, gastrointestinal
track disorders, wound healing, skin infections, aging, intoxications, tuberculosis,
chicken pox, hepatitis, leprosy etc. It is also being explored to treat deadly
diseases like AIDS, diabetes, asthma, heart diseases, arthritis and others.
Panchagavya and Ark have been found to be useful against flu viruses (Chauhan
et al., 2001; Dhama et al., 2005b).
Cow urine has been demonstrated to have potent anti-cancer activity and bioenhancer
of drugs (Dhama et al., 2005c). Gauloka Peya
(meaning 'drink from the land of cow') is having medicinal properties and is
prepared by incorporating distilled and sterile cow urine mixed with water and
herbs like brahmi and basil (Rahman, 2010).
CONCLUSION AND FUTURE PERSPECTIVES
The development in the field of molecular biology and nanobiotechnology has increased the versatility of therapeutic approaches to control various diseases and ailments. Thus, contributing to the improvement of health status of individual and accelerated growth of biological science at a rapid pace has the potential for significant advances in medical and veterinary public health. DNA technologies have revolutionalized modern science and find its application in the management of many incurable and chronic diseases of humans as well as animals. Stem cell therapy has the ability to change the face of human diseases as well as to alleviate sufferings. Nowadays, principles that govern the immune response are used in tailor-made vaccines against many noninfectious human diseases viz. cancers and autoimmune disorders. Nutritional immunomodulation helps in better economic outcome in the livestock sector. The concept of probiotic supplementation in feed is promising to maintain growth and production along with protecting health and boosting immunity without any side effects or public health hazard. Similarly, Ayurveda and Rashayanas are also preferred by a large portion of Indian population as they are cost effective and free from side effects. The IgY technology offers great future opportunities for designing prophylactic strategies against infectious GI diseases in humans and animals. Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in near future. The application of all these therapies under various circumstances will ultimately safeguard health. Nevertheless, it should always be kept in mind that application of various novel therapies require judicious approaches to become fruitful in a better way.
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