hafiz waseem

1. UNIVERSITY OF EDUCATION , LMC
SUBMITTED BY,
HAFIZ M WASEEM
MCF1901171
SEMESTER 4TH
DEPARTMENT :MSC ZOOLOGY (EVE)
COURSE TITLE :ENTOMOLOGY
SUBMITTED TO,
DR SAJIDA NASEEM

2. GROUP # 4
GROUP MEMBERS
1. M SAQIB
2. H. M. WASEEM
3. MIRAB SHEHZADI
4. TOOBA ZULFIQAR
5. SYED HUSSAIN ALI
6. KHADIJA DAR
GROUP TOPIC :
ROLE OF SPIDER VENOM IN MEDICAL FIELD
ASSIGNED PARAMETER :
THERAPEUTIC ROLE OF SPIDER VENOM FOR THE
TREATMENT OF DIFFERENT DISEASE

3. CONTENTS
1. SYSTEMATIC POSITION OF SPIDER VENOM
2. INTRODUCTION OF SPIDER VENOM
3. CEREBROVASCULAR DISEASE
4. ALZHEIMER DISEASE
5. EPILEPSY
6. SPIDER VENOM PREVENTS THE DEATH OF HEART
MUSCLE CELLS
7. POST STROKE BRAIN DAMAGE
8. FATAL SPIDER VENOM COULD PROTECT AGAINST POST
STROKE BRAIN DAMAGE
9. DRAVET SYNDROME IS A RARE AND LIFE-THREATENING
FORM OF EPILEPSY
10.MUSCULAR DYSTROPHY
11.DRAVET SYNDROME IS A RARE AND LIFE-THREATENING
FORM OF EPILEPSY
12.SPIDER VENOM HELPS HEARTS KEEP THEIR RHYTHM
13.UTILISING SPIDER VENOM FOR DIABETES TREATMENT
14.SPIDER VENOM US TO RELAXES THE SMOOTH MUSCLE.
CONCOLUSION
REFRENCES

4. SYSTEMATIC POSITION OF SPIDER
• Kingdom : Animalia
• Phylum : Arthropoda
• Class : Arachnida
• Order : Araneae
• Suborder : Araneomorphae
: Mygalomorphae
Two major suborders
Araneomorphae (“modern”spiders)
Mygalomorphae (“primitive” spiders)
Araneomorphs represent >90%of all known spider species
Mygalomorphs are more sustainable and convenient source of venom due
to their large venom glands . Longevity (Live for over 25 years )
INTRODUCTION OF SPIDER VENOM
Spiders are the most successful venomous animals with an estimated 100,000 extant species .
The vast majority of spiders employ a lethal cocktail to rapidly subdue their prey, which are
often many times their own size. However, despite their fearsome reputation, less than a handful
of these insect assassins are harmful to humans. Nevertheless, it is this small group of medically
important species that first prompted scientists more than half a century ago to begin exploring
the remarkable pharmacological diversity of spider venom.
Amongst the ranks of animals that employ venom for their survival, spiders are the most
successful, the most geographically widespread, and arguably consume the most diverse range of
prey. Although the predominant items on a spider’s dinner menu are other arthropods, larger
species will readily kill and feed on small fish, reptiles, amphibians, birds, and mammals. Thus,
spider venoms contain a wealth of toxins that target a diverse range of receptors, channels, and
enzymes in a wide range of vertebrate and invertebrate species.
1) CEREBROVASCULAR DISEASE

5. DEFINITION
the word cerebrovascular refers to blood flow in the brain. The term cerebrovascular
disease includes all disorders in which an area of the brain is temporarily or permanently affected
by ischemia or bleeding and one or more of the cerebral blood vessels are involved in the
pathological process.
INTRODUCTION
The word cerebrovascular is made up of two parts – "cerebro" which refers to the large part of
the brain, and "vascular" which means arteries and veins. Together, the word cerebrovascular
refers to blood flow in the brain. The term cerebrovascular disease includes all disorders in
which an area of the brain is temporarily or permanently affected by ischemia or bleeding and
one or more of the cerebral blood vessels are involved in the pathological process.
Cerebrovascular disease includes stroke, carotid stenosis, vertebral stenosis and intracranial
stenosis, aneurysms, and vascular malformations.
Cerebrovascular disease comprises stroke and other complications involving brain blood vessels.
This clinical syndrome affects approximately 16.9 million individuals per year worldwide and is
the second leading cause of death. The World Health Organization (WHO) defined stroke as a
“clinical syndrome of rapid onset of focal (or global, as in subarachnoid hemorrhage) cerebral
deficit, lasting more than 24 h (unless interrupted by surgery or death), with no apparent cause
other than a vascular one”. However, this concept is now considered obsolete. Recently, a
consensus document for an updated definition of stroke for the 21 st century was proposed. In
summary, according to Sacco et al. “a CNS infarction is defined as brain, spinal cord, or retinal
cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical

6. evidence of permanent injury. It also broadly includes intracerebral hemorrhage and
subarachnoid hemorrhage.
HISTORY OF CEREBROVASCULAR DISEASE
A humoral imbalance was seen as the causation. In the 17th century, Johannes Wepfer, a Swiss
physician, first demonstrated that apoplexy was caused by an intracranial hemorrhage; Thomas
Willis, an English anatomist, explored the role of the cerebral arteries. Stroke became a
cerebrovascular disease. By the 19th century, based on extensive clinico-pathological correlates
initiated at the Paris Medical School, a vascular basis was firmly established and a range of
pathologies determined. Apoplexy was considered too imprecise, and the term abandoned in
favor of the term "cerebro-vascular accident" and latterly stroke. Although physicians of the 19th
century utilized a wide variety of therapies in the treatment of stroke, with particular emphasis on
blood letting, therapeutic nihilism dominated stroke management well into the 20th century.
Following the mid 20th century work by C. Miller Fisher, with the recognition of the importance
and the therapeutic implication of the carotid artery in stroke, the specialty of stroke medicine
came into being. Therapeutic nihilism was replaced by an increasing armamentarium of
therapeutic interventions.
GLUTAMATE RECEPTORS
Aiming to prevent or minimize brain damage resultant from ischemic cell death, several
approaches have focused on potential neuroprotective treatment and/or therapeutic targets for
stroke. First, considering that excessive activation of glutamate receptors is involved in brain
damage following stroke, both agonist and antagonist of ionotropic glutamate receptors and their
effects in exacerbating and attenuating, respectively, the post-hypoxic/ischemic outcome have
been evaluated. However, multiple human trials of glutamate synthetic antagonists have failed to
indicate effective neuroprotection against stroke whereas side effects associated with this class of
compounds have impeded clinical application. In this context, search for new options of non-
toxic and effective antagonists has been stimulated.
TREATMENT
1) ACYLPOLYAMINES

7. Glutamate receptor antagonists have been found in arthropod venoms, mostly acylpolyamines,
evaluated for alleviating brain damage caused by stroke in preclinical models. Polyamine amide
toxins or acylpolyamines are selective non-competitive glutamate receptor (Glu-R) antagonists
able to block open channels, serving as a platform to design new drugs for the treatment of stroke
in humans.
2) ARGIOTOXIN-636 BLOCKS GLUTAMATE RECEPTORS
For instance, the small molecule NPS-1506 (delucemine), whose design is based on argiotoxin-
636 (acylpolyamine isolated from Argiope aurantia), blocks glutamate receptors of the NMDA-
type in neurons, thus preventing excessive Ca2+ influx during ischemia, which produces
neuroprotective effects. NPS 1506 also attenuates memory dysfunction and reduces neuronal
damage induced in several stroke models. Unfortunately, the use of this drug as a stroke injury
reducer has been discontinued in clinical stages. In 2005, the molecule, now called delucemine,
was evaluated for use as an antidepressant; however, after successful outcomes in drug
development phase I, research on this drug was suspended. Unexpectedly, in 2006, Johnson &
Johnson Pharmaceuticals acquired intellectual property related to delucemine, and later,
apparently, kept the project on hold.
3) POLYAMINE VENOM FROM THE FUNNEL WEB SPIDER AGELENOPSIS
APERTA
Venom from the funnel web spider Agelenopsis aperta contains a mixture of atypical polyamine
toxins forming a fraction termed FTX. FTX abolishes Ca 2+ action, resulting in plateau
potentials, and inhibits voltage-sensitive calcium channel function (VSCC) in adult cerebellar
Purkinje cells (P-type channel is the predominant type of Ca2+ channel). The active component
of crude FTX, FTX-3.3, was isolated and its electrophysiological properties studied, showing
that it preferentially blocks P-type VSCC, also blocking N-and L-type VSCC. Considering the
potential involvement of VSCC in cellular Ca 2+ loading during ischemic depolarization, these
toxins, in modified form, could be useful neuroprotective agents in the case of stroke.

8. 4) TOXIN PNTX4-3, ISOLATED FROM VENOM OF THE SPIDERPHONEUTRIA
NIGRIVENTER INTERACTS WITH GLUTAMATERGIC
NEUROTRANSMISSION
In relation to peptides, toxin PnTx4-3, isolated from venom of the spiderPhoneutria nigriventer,
interacts with glutamatergic neurotransmission. Assays performed using rat brain
cynaptosome.revealed a dose-dependent inhibition of glutamate uptake; however, action studies
in animal models for neurological disorders, focused on evaluating the neuroprotective effect
have not yet been completed.
5) PEPTIDES, PHTX3-3 AND PHTX3-4, ALSO ISOLATED FROM P.
NIGRIVENTER
Two other peptides, PhTx3-3 and PhTx3-4, also isolated from P. nigriventer with
neuroprotective action against ischemia neuronal damage, have been purified. These compounds
represent broad-spectrum Ca 2+ channel blockers able to abolish both the calcium-dependent
glutamate release and increase (Ca2+ ) induced by K + depolarization from synaptosomes.
Importantly, PhTx3 decreases neuronal death and loss of neurotransmission in hippocampus
CA1 tested in anin vitro ischemia model.
6) ACIDOSIS HIGHLIGHTED AS A COMMON FEATURE OF ISCHEMIA
Acidosis has been highlighted as a common feature of ischemia, playing a critical role in brain
injury. Acidosis activates Ca 2+ -permeable acid-sensing-ion channels (ASICs), causing an influx
of calcium ions into neurons, thus inducing glutamate receptor-independent, Ca 2+−dependent,
neuronal injury inhibited by ASIC blockers. This calcium influx can be blocked by PcTX venom
obtained from the tarantula Psalmopoeus cambridgei, a specific blocker of the ASIC1a subunit.
In the case of focal ischemia, intracerebrovascular (ICV) injection of ASIC1a blockers protects
the brain from ischemic injury and apparently does so more potently than glutamate antagonism.
2) ALZHEIMER’S DISEASE

9. HISTORY OF ALZHEIMER’S DISEASE
On November 3, 1906, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported “A
peculiar severe disease process of the cerebral cortex” to the 37th Meeting of South-West
German Psychiatrists in Tubingen, He described a 50-year-old woman whom he had followed
from her admission for paranoia, progressive sleep and memory disturbance, aggression, and
confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary
tangles in the brain histology. It excited little interest despite an enthusiastic response from
Kraepelin, who promptly included “Alzheimer's disease” in the 3ih edition of his text Psychiatrie
in 1910. Alzheimer published three further cases in 1909 and a “plaque-only” variant in 1911,
which reexamination of the original specimens in 1993 showed to be a different stage of the
same process, Alzheimer died in 1915, aged 51, soon after gaining the chair of psychiatry in
Breslau, and long before his name became a household word.
DEFINITION OF ALZHEIMER’S DISEASE
Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys memory
and thinking skills and, eventually, the ability to carry out the simplest tasks. In most people with
the disease—those with the late-onset type—symptoms first appear in their mid-60s.
INTRODUCTION OF ALZHEIMER’S DISEASE
Alzheimer’s disease (AD) is a form of dementia characterized by the loss of cognitive function
involving memory loss, deficits in comprehension and speech, and a lower capacity for
recognizing objects and making plans. Dementia affects 35.6 million people worldwide, wherein
AD represents 60-70 % of these cases. The risk of developing AD increases proportionally with
age; thus, considering the progressive higher life expectancy, it is estimated that the frequency of
cases will double by 2030 and triple by 2050, making AD an important problem of public health.
PATHOLOGY OF ALZHEIMER’S DISEASE
The main pathological hallmark found in AD patients is the presence of amyloid-β (Aβ)
aggregates and neurofibrillary tangles of tau protein. Misbalance between production of peptide
Aβ, naturally found in neurons, and clearance causes its accumulation and aggregation [37]. In
turn, tau protein, also normally found in neurons, can be hyperphosphorylated, aggregating and
forming the filamentous structures that ultimately originate the tangles. Due to these
neuropathological alterations, neuronal loss occurs, especially in the hippocampus and basal
forebrain, as well as synaptic dysfunction and neurotransmitter deficits.
TREATMENT OF ALZHEIMER’S DISEASE
1) ACETYLCHOLINESTERASE INHIBITORS (DONEPEZIL, GALANTAMINE
AND RIVASTIGMINE)

10. Therapeutic approaches remain focused on the symptomatic treatment of the disease, as there is
no approved drug able to effectively modify the progression of AD in patients. Unfortunately,
pharmacological companies have obtained ineffective results in relation to safety or efficacy in
advanced clinical trials. Two classes of symptomatic drugs currently in use are the
acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine), which increase the
availability of acetylcholine at the synaptic cleft, and the N-methyl-D-aspartic acid receptor
antagonists (memantine), used to prevent glutamatergic excitotoxicity. These drugs have been
tested in patients with mild to moderate AD. Another approach aimed at treating symptoms in
patients with mild-to-moderate AD include the use of immune globulin intravenous (IGIV 10
%), a biologic agent containing human immunoglobulin IgG antibodies with anti-inflammatory
and immunomodulating properties. IGIV binds to oligomeric and amyloid-β fibrils to reverse
neurotoxic events in clinical and preclinical settings.
2) PEPTIDE TX3-1 EXTRACTED FROM SPIDER VENOM FROMP.
NIGRIVENTER
The effect of peptide Tx3-1, a selective blocker of A-type K +currents (I A ), extracted from
spider venom fromP. nigriventer, was evaluated in cognitive models in mice. Results showed the
ability of the toxin to enhance both short- and long-term memory consolidation in mice tested in
the novel object recognition task. Moreover, Tx3-1 restored memory of Aβ 25–35 -injected mice
and exhibited higher potency to improve memory of Aβ 25–35 -injected mice when compared to
control group.
3) EPILEPSY
DEFINE EPILEPSY
Epilepsy is a central nervous system (neurological) disorder in which brain activity becomes
abnormal, causing seizures or periods of unusual behavior, sensations, and sometimes loss of
awareness. Anyone can develop epilepsy. Epilepsy affects both males and females of all races,
ethnic backgrounds and ages.

11. HISTORY OF EPILEPSY
The first connection between heredity and epilepsy was made in 1903 by Lundborg (1868–
1943), a Swedish physician, notorious for his views on eugenics and racial hygiene, who
published his research on the genetics of progressive myoclonic epilepsy first described by
Heinrich Unverricht in 1891 (1853–1912)
During the last decades, approximately 1700 bioactive candidates have been discovered in spider
venoms. Some of these compounds present neuroprotective and antiepileptic effects acting on
voltage-sensitive Na + and Ca 2+ channels or on glutamate receptors. The observed effects are
attributed to small molecules, found in spider venoms, that present the ability to recognize and
antagonize mammalian receptors highly similar to invertebrate receptors, the main target of
spiders.
INTRODUCTION OF EPILEPSY
Epilepsy is characterized by a persistent predisposition to generate spontaneous epileptic seizures
and by the psychological, neurobiological, social, and cognitive consequences associated with it.
In relation to treatment, antiepileptic drug (AED) therapy aims to eliminate or reduce seizures to
the maximum degree possible, thus decreasing adverse effects, helping patients in maintaining or
retrieving their usual activities, and conserving a normal lifestyle. Nevertheless, despite drug
availability, approximately 30 % of patients with epilepsy continue to live with uncontrolled
seizures. These patients are regarded as therapy-resistant or refractory to the existing AEDs.
In this scenario, arthropod venoms may represent an extraordinary source of bioactive molecules
that act with selectivity and specificity in the mammalian CNS. This is sustained by a growing
number of studies that show its true efficacy in several animal epilepsy models. Such is the case
of scorpions that possess venoms with extremely specific and potent peptides that interact
specifically with Na + , K + , Cl − and Ca2+ ion channels, and also modulate GABAergic
neurotransmission.
TREATMENT
1) POLYAMINE TOXINS OF NEPHILIA CLAVATA
Neuroactive effects of polyamine toxins obtained from spiders were first recorded by Kawai et
al. in 1982, in the venom of Nephilia clavata. They demonstrated that JSTX blocks
glutamatergic synapses in the mammalian brain. Later, Himi et al.demonstrated that JSTX
antagonized AMPA-induced seizures with no behavioral toxicity at the effective dosages. Later,
JSTX-3 was synthesized and antagonized quisqualate-induced seizures; however, it did not block
NMDA or kainic acid (KA)-induced convulsions, suggesting a potential activity on non-NMDA
receptors in vertebrate CNS.
2) ARGIOTOXINS IDENTIFIED FROM THE VENOM OF THE SPIDER ARGIOPE
LOBATA

12. Argiotoxins identified from the venom of the spider Argiope lobata and other members of the
Araneidae family presented neuroprotective action against KA and inhibited cell death
mechanisms that involve ionotropic GluR. Moreover, argiotoxin-636 displayed an antiepileptic
effect against NMDA-induced and audiogenic seizures in mice.
3) POLYAMINIC COMPOUNDS ALSO OBTAINED FROM THE VENOM OF
THE SPIDER A. APERTA (AG2)
Other polyaminic compounds also obtained from the venom of the spider A. aperta (AG2)
exhibited antiepileptic action by blocking KA-, picrotoxin (PICRO)- and bicuculline (BIC)-
induced seizures in rats.
4) PARAWIXIN2 (FRPBAII), A TOXIN ISOLATED FROM THE VENOM
OF PARAWIXIA BISTRIATA SPIDER
Parawixin2 (FrPbAII), a toxin isolated from the venom of Parawixia bistriata spider, has now
become a product sold by Santa Cruz Biotechnology. This compound selectively inhibits
synaptosomal GABA and glycine reuptake in a dose-dependent manner with little or no effect on
monoamine or glutamate transporters. Also, parawixin2 showed protection against PILO-,
PICRO-, KA- and PTZ-induced seizures and PTZ-induced kindling. Antiepileptic activity was
also identified when parawixin2 was injected into the substantia nigra pars reticulata (SNr).
5) PARAWIXIN10 WAS ISOLATED FROM SPIDER VENOM
Similarly, parawixin10 was isolated from the same spider venom and demonstrated protection
against KA, NMDA, and PTZ induced seizures in a dose-dependent manner. However, in
synaptosomes from rat cerebral cortices it increased L-Glu and glycine uptake, whereas GABA
uptake did not change, suggesting high-affinity mediation.
6) NEUROACTIVE FRACTION OBTAINED FROM SPIDER SCAPTOCOSA
RAPTORIAL(SRTX1)
A neuroactive fraction obtained from spider Scaptocosa raptorial(SrTx1) also inhibited GABA
uptake, further presenting antiepileptic effects in an acute GABAergic model of seizure
induction. The SrTx1.3 component from this fraction also protected against BIC-evoked seizures
in a dose-dependent manner.
7) SPIDER VENOM Ω-AGATOXIN IVA, A PEPTIDE ISOLATED FROM A.
APERTA
Animals submitted to intense sound stimulation were protected from tonic seizures by the
administration of ω-agatoxin IVA, a peptide isolated from A. aperta, suggesting that it is able to
antagonize NMDA receptor function. Also, from the same spider, agatoxin-489 was able to
block KA-induced seizures.
8) SPIDER VENOM FROM THE SOLITARY WASP PHILANTHUS TRIANGULUM

13. Similar to spider venom, the venom from the solitary wasp Philanthus triangulum contains a
group of polyamine toxins called philanthotoxins (α-, β-, γ-, δ-PhTx), under investigation since
the 1980s due to their remarkable activity in glutamatergic receptors. Furthermore, a
neuroprotective and inhibitory effect on neuronal nicotinic Ach receptors has been reported for
PhTx toxins and their analogues. Despite the fact that an antiepileptic activity of these toxins has
not been described in an experimental model, their selective antagonism in ionotropic glutamate
receptors and possible neuroprotective effect represent at least a possibility that deserves to be
further investigated.
4) SPIDER VENOM PREVENTS THE
DEATH OF HEART MUSCLE CELLS
A heart attack is a form of coronary disease that occurs suddenly. Damage to your heart muscle
from a heart attack may mean your heart can no longer pump as well as it should. Diabetes.
Having diabetes increases your risk of high blood pressure and coronary artery disease.
Cardiovascular events refer to any incidents that may cause damage to the heart muscle. The
heart is a busy organ, constantly pumping blood filled with oxygen and nutrients through your
arteries, into the heart muscle (myocardium). Any interruption of blood flow will lead to an
injury, or infarction.
INTRODUCTION
Researchers in Australia are in the process of converting a deadly local spider’s venom into a
drug that could be used to reduce heart damage after an MI.
TREATMENT
Glenn King, a professor at the University of Queensland, and his team found the venom of the
Fraser Island funnel-web spider—which, to date, has killed 13 people with its lethal bite—
contains a molecule that can prevent brain damage during a stroke and slow cardiac damage after
a heart attack. The molecule seems to prevent the death of cardiomyocytes, possibly keeping a
heart alive longer.
King’s team has isolated the molecule in question and is working to incorporate it into a
therapeutic drug, according to News.
TREATMENT
1) THE VENOM OF THE FRASER ISLAND FUNNEL-WEB COULD PREVENT
THE DEATH OF HEART MUSCLE CELLS
In an Australian medical breakthrough, scientists have discovered the venom of the deadly
funnel-web spider could be used to treat heart attack victims. The venom of the Fraser Island

14. funnel-web could prevent the death of heart muscle cells, minimising the damage done to the
heart and possibly keeping it alive longer, researchers say.The discovery builds on a similar
breakthrough using the same spider venom. Queensland scientists recently identified a molecule
that can prevent brain damage during a stroke and are exploring what else it can do.
2) CARDIOTOXIC EFFECTS OF LOXOSCELES INTERMEDIA SPIDER VENOM
Loxosceles spider bites cause many human injuries worldwide. Injections in mice of whole
Loxosceles (L.) intermedia venom or a recombinant toxin (rLiD1) produce systemic symptoms
similar to those detected in envenomed humans. This animal model was used to characterize the
effects of Loxosceles intermedia venom in cardiac tissues.
3) L. INTERMEDIA SPIDER VENOM AND THE LOXTOX RLID1 PLAY A KEY
ROLE IN HEART DYSFUNCTION.
In addition, rLiD1 binding to cardiomyocytes was demonstrated by immunofluorescence and
confocal microscopy. Furthermore, isolated perfused heart preparations and ventricular
cardiomyocytes from envenomed mice showed heart function impairment, and a significant
increase of I(Ca,L) density and intracellular Ca(2+) transients, respectively. Thus, L. intermedia
spider venom, as shown through the use of the recombinant toxin rLiD1, causes cardiotoxic
effects and a protein from the sphingomyelinase D family plays a key role in heart dysfunction.
Thus, L. intermedia spider venom and the Loxtox rLiD1 play a key role in heart dysfunction.
4) BROWN SPIDER VENOM HAS A COMPLEX COMPOSITION
DERMONECROTIC TOXIN.
Brown spider (Genus Loxosceles) bites are normally associated with necrotic skin degeneration,
gravitational spreading, massive inflammatory response at injured region, platelet aggregation
causing thrombocytopenia and renal disturbances. Brown spider venom has a complex
composition containing many different toxins, of which a well-studied component is the
dermonecrotic toxin. This toxin alone may produce necrotic lesions, inflammatory response and
platelet aggregation. Biochemically, dermonecrotic toxin belongs to a family of toxins with 30-
35 kDa characterized as sphingomyelinase-D. Here, employing a cDNA library of Loxosceles
intermedia venom gland, we cloned and expressed two recombinant isoforms of the
dermonecrotic toxin LiRecDT2 (1062 bp cDNA) and LiRecDT3 (1007 bp cDNA) that encode
for signal peptides and complete mature proteins.
NEW SOUTH WALES AND VICTORIA ARE NOW WORKING TO TURN THAT
PROTEIN MOLECULE INTO A DRUG.
Professor Glenn King from the University of Queensland and his team have managed to isolate
the molecule from thousands in the spider’s venom. Researchers in Queensland, New South
Wales and Victoria are now working to turn that protein molecule into a drug.

15. “What it's doing is preventing the death of heart muscle cells, so even in patients that survive a
heart attack or cardiac arrest they end up with a fairly damaged heart, part that won't grow back,”
Professor King told News. “We found that it worked for stroke, so we asked the question if it
would work for ischemic events in the heart and now that we're shown that it does protect the
heart, the question is, is it useful for preventing ischemic event in other organs?”
5) FATAL SPIDER VENOM COULD PROTECT AGAINST
POST-STROKE BRAIN DAMAGE
INTRODUCTION
If trials show that the compound works, it could potentially transform the treatment of stroke
patients. There are no drugs on the market that can protect the brain from stroke injuries. The
best hospitals can offer are infusions of clot-busting drugs if a clot is to blame, or a surgical
procedure called endovascular thrombectomy, which physically pulls the clot from the brain.
When a stroke attacks, blood flow to the brain is suddenly interrupted. Brain cells are deprived of
oxygen and immediately begin to die. In fact, up to 1.9 million brain cells succumb every
minute. Stroke can happen to anyone, and it claims six million lives worldwide each year. A
further five million stroke survivors are left with a permanent disability.
THE UNIVERSITY OF QUEENSLAND AND MONASH UNIVERSITY
DISCOVERED APEPTIDE IN THE VENOM OF FUNNEL-WEB SPIDERS
SMALL PROTEIN, HI1A, THAT POTENTLY BLOCKS ACID-SENSING
ION CHANNELS IN THE BRAIN
Professor Glenn King and his research partners at The University of Queensland and Monash
University discovered a peptide in the venom of funnel-web spiders that could drastically reduce
brain damage following stroke. “We believe we have, for the first time, found a way to minimise
the effects of brain damage after a stroke. “We discovered a small protein, Hi1a, that potently
blocks acid-sensing ion channels in the brain, which are key drivers of brain damage after stroke.
Remarkably, this peptide was found in venom of the lethal Australian funnel-web spider.”
During preclinical studies, researchers found a single dose of Hi1a administered up to eight
hours after stroke protected brain tissue and drastically improved neurological performance.
“We found brain damage was reduced by 80 per cent when Hi1a was administered two hours
after stroke. Even when administered eight hours after stroke onset, the amount of brain damage
was reduced by about 65 per cent,”
PROFESSOR KING SAID

16. “This is a remarkably long window of opportunity for treatment, which makes it a promising
drug lead, as about 60 per cent of stroke patients do not reach an emergency room until at least
two hours after onset of stroke. It would be particularly useful for patients in rural and regional
areas, who need to travel further to access their nearest hospital.”If clinical trials are successful,
Hi1a could transform treatment and outcomes for stroke patients, as there are currently no stroke
treatments on the market that can protect the brain. Strokes occur when blood flow to the brain is
interrupted and the brain is starved of oxygen. About 85% of strokes are caused by blockages in
blood vessels in the brain, with the rest due to bleeds when vessels rupture. Approximately six
million people a year die from stroke, making it the second largest cause of death worldwide
after heart attacks.
When a stroke occurs, the brain becomes deprived of oxygen due to the reduced blood supply.
Without oxygen, lactic acidosis sets in. This turns on acid-sensing ion channels which initiate a
deadly chain reaction that spreads through the brain like a wave. Like destruction in the wake of
a tsunami, this wave destroys neurons, the working units of the brain.
DURING ANAEROBIC GLYCOLYSIS THE OXYGEN LEVEL IN THE
BRAIN DROPS.
When a stroke happens, the oxygen level in the brain drops. This forces the brain to burn its
primary fuel, glucose, very differently. Instead of oxidising glucose for energy, the brain
switches to a process called anaerobic glycolysis. The reaction releases energy to keep the brain
working, but it also produces acid, which can cause brain cells to die.
TREATMENT FOR STROKE
There is only one approved drug treatment for stroke caused by a blood clot, which works to
dissipate the clot. Unfortunately this drug treatment also thins the blood, and therefore it is
unsuitable for patients whose stroke is caused by a haemorrhage rather than blockage of an
artery. “If Hi1a also proves to be safe for patients with stroke caused by a brain haemorrhage, it
could be administered in the ambulance without the need of a brain scan. This would minimise
fatalities and provide much better outcomes for survivors of stroke in terms of minimising brain
damage.
THE PEPTIDE, CALLED Hi1a, CAN BE GIVEN AS SOON AS A STROKE
IS DETECTED.
Researchers at IMB have uncovered a peptide sourced from spider venom that blocks the and
acid-sensing channel, and stops the wave of post-stroke destruction. The peptide, called Hi1a,
can be given as soon as a stroke is detected.Our researchers discovered Hi1a in one of the
world’s deadliest spiders the Fraser Island funnel-web.
WE CANNOT REBUILD NEURONS AFTER A STROKE
But unlike devastated towns after a tsunami, you cannot rebuild neurons after a stroke; the
damage is irreversible. Every second counts. For every minute that the wave is left unchecked,

17. two million neurons are permanently lost. There is no current treatment available that can be
administered outside of a hospital – and for many, the time it takes to get to a hospital means the
treatment comes far too late, or not at all.
A SINGLE SMALL DOSE OF THE SPIDER VENOM MOLECULE
PROTECTED NEURONS FROM INDUCED STROKES.
In a series of studies on rats, King showed that a single small dose of the spider venom molecule
protected neurons from induced strokes. The compound works by blocking what are called ion
channels in cells, specifically those that respond to the onset of acidic conditions in the brain.
This article was amended on 22 March 2017 to clarify that there are a several species of funnel
web spiders.
TRANSLATING VENOM INTO DRUGS
Professor Glenn King is a biochemist and structural biologist whose expertise lies in translating
venom-derived peptides into human drugs and natural insecticides. His lab maintains the most
extensive collection of venoms in the world, which includes venoms from more than 650 species
6) DRAVET SYNDROME IS A RARE AND LIFE-
THREATENING FORM OF EPILEPSY
Dravet syndrome is a rare and life-threatening form of epilepsy that strikes children in the first
year of life. It is caused by a mutation that reduces the amount of NaV1.1, a key sodium channel
in the brain that is critical for regulating brain excitability.
Working in collaboration with Steven Petrou at the Florey Institute of Neuroscience and Mental
Health, King’s team found a peptide in funnel-web spider venom that restores normal function of
this channel and eliminates seizures.
“We started giving Dravet syndrome mice the spider-venom peptide after they developed serious
seizures, and within four days we had eliminated all the seizures and the mice were saved from
premature death,” King says. “That is really exciting, but the issue now is how to best deliver
that drug to the brain, and that is a technical issue that needs to be solved before moving into

18. © The University of Queensland
A toxin synthesized from the venom of a spider may offer an alternative to today's erectile
dysfunction drugs, a new study suggests.
DEFINE
Erectile dysfunction (impotence) is the inability to get and keep an erection firm enough for sex.
Having erection trouble from time to time isn't necessarily a cause for concern.
HISTORY

19. Francois de la Peyronie is known for his original description of Peyronie's disease in 1743, with
the assumption at the time that he was himself a sufferer of the disease. In 1863, Eckhard
published the first studies of an electrically induced penile erection in a dog
INTRODUCTION
Penile erection is a complex process initiated by activation of parasympathetic pelvic nerves,
resulting in arterial dilatation followed by relaxation of corpora cavernosa.Nitric oxide (NO)
plays a major role in the generation and maintenance of intracavernous pressure and penile
erection. NO, which is released from nitrergic nerves within the trabecular and arterial tissues as
well as by the endothelial tissue of penile arteries, exerts its relaxing action by activating soluble
guanylyl cyclase. This causes an increase in intracellular cGMP which relaxes the smooth
muscles of the cavernous body and results in penile erection.
TREATMENT
1) FOR TREATMENT OF ERECTILE DYSFUNCION (ED), INCLUDING
SILDENAFIL , TADALAFIL, AND VARDENAFIL DRUG .
There are several drugs on the market today for treatment of erectile dysfuncion (ED), including
sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil (Levitra®). These drugs all affect
phosphodiesterase type 5 (PDE5), which is present in large amounts in the penis. Inhibition of
PDE5 leads to increased levels of cGMP and hence increased blood flow to the penis. The
aforementioned PDE5-blocking drugs have similar side effects including headache, flushing,
dyspepsia, nasal congestion, impaired vision, photophobia and blurred vision. Hence, there is a
need for better drugs with fewer side effects for the treatment of ED.
2) THE TOXIN, NAMED PNTX2-6, COMES FROM THE BITE OF THE
BRAZILIAN WANDERING SPIDER (PHONEUTRIA NIGRIVENTER).
The toxin, unpoetically named PnTx2-6, comes from the bite of the Brazilian wandering spider
(Phoneutria nigriventer). In humans, a bite from a wandering spider is very painful. What's
more, male victims may find themselves with priapism, or unrelenting and painful erection. It
was this symptom, turning up in emergency rooms after spider bites in Brazil, that first alerted
researchers to the potential of PnTx2-6 as an erectile dysfunction (ED) drug.
The toxin has been shown to improve erections in rats with hypertension and diabetes; now,
researchers have tested it in aging mice and found that the toxin is effective in reversing age-
related ED as well.
"It's working in aging, which is a natural process," study researcher Kenia Nunes, a physiologist
at Georgia Health Sciences University, told LiveScience. "It's not just in disease."

20. 7) MUSCULAR DYSTROPHY
DEFINE
The muscular dystrophies (MD) are a group of more than 30 genetic diseases characterized by
progressive weakness and degeneration of the skeletal muscles that control movement. Some
forms of MD are seen in infancy or childhood, while others may not appear until middle age or
later
HISTORY
In the 1860s, descriptions of boys who grew progressively weaker, lost the ability to walk, and
died at an early age became more prominent in medical journals. In the following
decade,[26] French neurologist Guillaume Duchenne gave a comprehensive account of the most
common and severe form of the disease, which now carries his name – Duchenne MD
INTRODUCTION
A drug developed by University at Buffalo scientists from a small protein found in spider venom
is moving forward as a promising treatment for Duchenne muscular dystrophy, a fatal genetic
disease affecting boys.
1) STUDIES SHOW DRUG PREVENTS CALCIUM INFLUX
In patients with dystrophy, genetic mutations weaken the membrane of muscle cells, enabling
large amounts of calcium to infiltrate the cells. This sets off a chain reaction that leads to muscle
degeneration.Laboratory studies show that AT-300 stops the dangerous calcium influx by
keeping mechanosensitive ion channels shut when muscle cells are stretched, says Sachs.

21. In addition, the modified form of the drug is designed to remain stable for a long time in the
human body. This could mean patients would need infrequent doses, which could hold down
costs.
According to a 2012 study out of the University of Buffalo, a particular protein found in spider
venom could work as a treatment for muscular dystrophy — an umbrella term for a number of
diseases that cause loss of muscle mass and eventual inability to walk, move, or swallow. The
study found that the protein helped stop muscle cells from deteriorating, and though it wasn’t a
cure, it assisted in slowing down the progression of the disease.
8) SPIDER VENOM HELPS HEARTS KEEP THEIR RHYTHM
TREATMENT
1) A PEPTIDE ISOLATED FROM THE VENOM OF THE
SPIDER GRAMMOSTOLA SPATULATA (PICTURE) INHIBITS ATRIAL
FIBRILLATION.
Although the sight of a large hairy spider is enough to give some people a heart attack, spider
venom may eventually be used to treat some heart conditions. In the 4 January issue of Nature,
Bode et al. (Nature, 409, 35–36) report that a peptide isolated from the venom of the
spider Grammostola spatulata (picture) inhibits atrial fibrillation. Atrial fibrillation,
characterized by disorganized atrial activity, occurs in patients suffering from valve disease,
hypertension, and chronic lung disease. It is the most common form of cardiac arrhythmia, and
can lead to further complications such as hypotension, pulmonary congestion, strokes and angina
pectoris.
Venom from a common South American tarantula spider may contain a protein that could
prevent atrial fibrillation.Research based on rabbits suggests that the peptide GsMtx-4 found in
the poison of 1 of the 800 different types of tarantula may be useful in tackling the cause of rapid
and chaotic electrical activity in the atria.

22. In the research, reported in Nature (2001; 409:35-36) a team of US and German scientists
investigated what kind of insect venom would block ion channels and prevent cells from
swelling and triggering atrial fibrillation.
2) AGENTS GSMTX-4 INITIATES A NEW CLASS OF ANTI-ARRHYTHMIC
SACs convert gradients of stress into gradients of electrical activity, and sustained mechanical
gradients can develop when systolic pressure and wall tension are high, conditions that are
present in the diseased heart. “It was well-known that cardiac wall stretch increases heart rate,
and we knew that these receptors were expressed in heart cells,” said Sachs. He teamed up with
Frank Bode and Mike Franz at Georgetown University to show that the peptide suppressed both
the incidence and duration of atrial fibrillation in rabbit hearts. They also showed that GxMtx-4
acts only during stretch activation, as it has no effect on the action potential of resting atrial cells.
“It also seems to have no acute effects on normal hearts in the absence of distension,” added
Sachs, although further toxicity analysis is required.
This finding of Bode et al. constitutes the first demonstration that SAC activation can generate
atrial fibrillation. The authors therefore suggest that GsMtx-4 initiates a new class of anti-
arrhythmic agents that could act on the cause, rather than the effects of cardiac arrhythmias.
3) THE PEPTIDE GSMTX-4 AS THE ACTIVE INGREDIENT.
The team, led by Professor Frederick Sachs of the State University of New York at Buffalo, tried
the venom from a number of spiders before finding that the poison from the
Chilean Grammostola spatulata (or Grammostola rosea) tarantula worked, with the peptide
GsMtx-4 as the active ingredient.
In the research, the team triggered the hearts of the rabbits into arrhythmia with a jolt of
electricity and then used extracts of the venom to suppress the abnormal heart rhythm that
followed.The research results also show that the peptide has no effect on an unstretched, or
normal, heart, suggesting that side effects should be minimal. An additional safety factor is that
the bite of the Chilean tarantula from which the venom comes is not harmful to humans.

23. 9) UTILISING SPIDER VENOM FOR DIABETES
TREATMENT
DEFINE
Diabetes is a chronic (long-lasting) health condition that affects how your body turns food into
energy.
Most of the food you eat is broken down into sugar (also called glucose) and released into your
bloodstream. When your blood sugar goes up, it signals your pancreas to release insulin. Insulin
acts like a key to let the blood sugar into your body’s cells for use as energy.
If you have diabetes, your body either doesn’t make enough insulin or can’t use the insulin it
makes as well as it should. When there isn’t enough insulin or cells stop responding to insulin,
too much blood sugar stays in your bloodstream.
HISTORY
The first known mention of diabetes symptoms was in 1552 B.C., when Hesy-Ra, an Egyptian
physician, documented frequent urination as a symptom of a mysterious disease that also caused
emaciation. Also around this time, ancient healers noted that ants seemed to be attracted to the
urine of people who had this disease.
INTRODUCTION
Diabetes mellitus is reaching epidemic proportions globally, and despite the range of currently
available anti-diabetes medications, many people still have inadequate metabolic control.
Arguably, one of the biggest success stories in recent times has been the discovery and clinical
realisation of exendin-4, a peptide originally isolated from the saliva of the venomous Gila
monster.
TREATMENT
1) TARANTULA SPIDER VENOM NON-TOXIC TO PANCREATIC BETA-CELLS
AND STIMULATES INSULIN SECRETION.
In relation to this, a key focus of our laboratory for many years has been drug discovery, and our
recent unpublished data has uncovered a novel peptides derived from tarantula spider venom.
These peptides have been shown to be non-toxic to pancreatic beta-cells and stimulates insulin

24. secretion. Furthermore, acute in vivo studies indicate that the novel peptides lowers blood
glucose concentrations in normal and diabetic rodents. Thus, spider venom derived peptides offer
an exciting new anti-diabetes opportunity.
To extend these important observations and progress a possible novel therapeutic drug regimen
for diabetes, we propose to:
 Discover novel, potential antidiabetic, venom-edrived peptides from various spiders
belonging to the Theraphosidae family
 Elucidate the mechanism of action of novel venom derived peptides in pancreatic islet
cells.
 Assess metabolic benefits of repeated daily dosing with novel peptides in preclinical
models of obesity-diabetes.
 Determine the molecular mechanisms involved in the beneficial effects.
10) SPIDER VENOM US TO RELAXES THE SMOOTH
MUSCLE.
TREATMENT
1) VIAGRA, LEVITRA AND OTHER ED DRUGS ON THE MARKET WORK BY
INHIBITING AN ENZYME CALLED PDE5.
Viagra, Levitra and other ED drugs on the market work by inhibiting an enzyme called PDE5.
To get an erection, a man's body must release nitric oxide, which relaxes the smooth muscle
around the arteries of the penis, allowing for his blood vessels to dilate. The nitric oxide is a first
step in a series of chemical reactions that allow this muscle relaxation to take place. One step in
the series is cGMP, a signaling molecule that acts to keep the muscles relaxed. PDE5 degrades
cGMP. That's a good thing for ensuring that erections don't last forever, but too much PDE5 can
mean an erection doesn't happen at all. By blocking the enzyme, PDE5 inhibitors solve the
problem.
2) PDE5, THE COMPOUND SEEMS TO TRIGGER NITRIC OXIDE RELEASE,
ACTING DIRECTLY TO RELAX THE SMOOTH MUSCLES.
The spider toxin works differently. Instead of affecting PDE5, the compound seems to trigger
nitric oxide release, acting directly to relax the smooth muscles. Because about 30 percent of
patients don't respond to PDE5 inhibitors, the toxin could provide an alternative to ED
treatments currently on the market, Nunes said.
In the new study, published online Aug. 23 in the Journal of Sexual Medicine, Nunes and her
colleagues injected aging and young rats with the toxin extracted from the spider venom. They
found that the toxin reversed age-related erectile dysfunction, offering hope that the toxin could
eventually move out of animal testing and into human use. The toxin has not yet been tested in
humans.

25. The researchers have since developed a synthetic version of the toxin. The next step, Nunes said,
is to make sure that the compound doesn't have any nasty effects beyond its intended purpose.
CONCLUSIONS
The high social and financial impact of neurological disorders have prompted an intense search
for therapeutic alternatives to the current array of drugs is urgent considering that most of these
disorders have an ineffective or only symptomatic treatment. In parallel, considering that
working with crude venom material involves many challenges (i.e.: high costs and bioethical
issues), recent advances in the fields of bioanalytics and bioinformatics, and innovative
approaches to drug discovery based on venomics and proteomics, bring hope to the discovery of
new bioactive molecules capable of treating several types of diseases, including neurological
disorders. Our review highlighted several promising toxins for the treatment of the top five
neurological disorders. Interestingly enough, some of these toxin compounds are already being
used as pharmacological tools or are being evaluated for the production of drugs for future
clinical use.
REFERENCES
 . Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nat Rev Drug
Discov. 2003;2(10):790-802. [ Links ]
 . King GF. Venoms to drugs: translating venom peptides into therapeutics. Aust
Biochem. 2013;44(3):13-15. [ Links ]
 . King GF. Venoms as a platform for human drugs: translating toxins into
therapeutics. Expert Opin Biol Ther. 2011; 11(11):1469-1484. [ Links ]
 . Santos LD, Pieroni M, Menegasso ARS, Pinto JRAS, Palma MS. A new scenario of
bioprospecting of Hymenoptera venoms through proteomic approach. J Venom Anim
Toxins incl Trop Dis. 2011;17(4):364-377. [ Links ]
 . World Health Organization.Neurological disorders: public health challengers. World
Health Organization, Switzerland; 2006. [ Links ]
 . De Boer HM, Mula M, Sander JW. The global burden and stigma of
epilepsy. Epilepsy Behav. 2008;12(4):540-546. [ Links ]
 . Marcangelo MJ, Ovsiew F. Psychiatric aspects of epilepsy. Psychiatr Clin North Am.
2007;30(4):781-802. [ Links
 Reach G, Pechtner V, Gentilella R, Corcos A, Ceriello A. Clinical inertia and its impact
on treatment intensification in people with type 2 diabetes mellitus. Diabetes Metab.
2017: S1262-3636(17)30467-6.
 Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture,
2005. Diabetologia. 2006 Feb;49(2):253-60.